The 46th EuroCongress on Drug Synthesis and Analysis (ECDSA-2017) was arranged within the celebration of the 65th Anniversary of the Faculty of Pharmacy at Comenius University in Bratislava, Slovakia from 5-8 September 2017 to get together specialists in medicinal chemistry, organic synthesis, pharmaceutical analysis, screening of bioactive compounds, pharmacology and drug formulations; promote the exchange of scientific results, methods and ideas; and encourage cooperation between researchers from all over the world. The topic of the conference, "Drug Synthesis and Analysis," meant that the symposium welcomed all pharmacists and/or researchers (chemists, analysts, biologists) and students interested in scientific work dealing with investigations of biologically active compounds as potential drugs. The authors of this manuscript were plenary speakers and other participants of the symposium and members of their research teams. The following summary highlights the major points/topics of the meeting.

Department of Biochemistry and Neurobiology Faculty of Materials Science and Ceramics AGH University of Science and Technology Mickiewicza 30 30059 Krakow Poland

Department of Crystallography Faculty of Mathematics Physics and Chemistry University of Silesia Bankowa 12 40006 Katowice Poland

Department of Food Science and Nutrition School of Environment University of the Aegean 81400 Myrina Lemnos Greece

Department of Inorganic Chemistry and Regional Centre of Advanced Technologies and Materials Faculty of Science Palacky University 17 listopadu 12 77146 Olomouc Czech Republic

Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Faculty of Pharmacy in Hradec Kralove Charles University Heyrovskeho 1203 50005 Hradec Kralove Czech Republic

Department of Pharmaceutical Chemistry Faculty of Pharmacy Comenius University Odbojarov 10 83232 Bratislava Slovakia

Department of Pharmaceutical Chemistry Faculty of Pharmacy National and Kapodistrian University of Athens Panepistimiopolis Zografou 15771 Athens Greece

Department of Pharmaceutical Chemistry Faculty of Pharmacy University of Belgrade Vojvode Stepe 450 11221 Belgrade Serbia

Department of Pharmaceutical Chemistry University of Vienna Althanstraße 14 A 1090 Vienna Austria

Department of Pharmaceutical Sciences College of Pharmacy Glendale Midwestern University 19555 N 59th Avenue Glendale AZ 85308 USA

Department of Pharmacognosy and Botany Faculty of Pharmacy Comenius University Odbojarov 10 83232 Bratislava Slovakia

Department of Pharmacognosy University of Vienna Althanstrasse 14 1090 Vienna Austria

Department of Pharmacy College of Pharmacy Seoul National University 1 Gwanak ro Seoul 08826 Korea

Department of Physical Medicine Medical University of Silesia Medykow 18 40752 Katowice Poland

Department of Synthesis Chemistry Faculty of Mathematics Physics and Chemistry University of Silesia Szkolna 9 40007 Katowice Poland

Institute of Chemistry University of Silesia Szkolna 9 40007 Katowice Poland

Institute of Genetics and Animal Breeding of the Polish Academy of Sciences Postepu 36A 05 552 Jastrzebiec Poland

Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences 3491 Baijin Road Guiyang 550014 China

Laboratory of Inorganic and Analytical Chemistry School of Chemical Engineering National Technical University of Athens Iroon Polytechniou 9 15780 Athens Greece

Laboratory of Pharmacological Neuroendocrinology Institute of Experimental Endocrinology Biomedical Research Center Slovak Academy of Sciences Dubravska cesta 9 84505 Bratislava Slovakia

State Key Laboratory of Functions and Applications of Medicinal Plants Guizhou Medical University 3491 Baijin Road Guiyang 550014 China

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The 46th EuroCongress on Drug Synthesis and Analysis (ECDSA-2017) [(accessed on 14 September 2017)]; Available online: https://sites.google.com/site/cfph2017.

Faculty of Pharmacy, Comenius University in Bratislava: History of the Faculty. [(accessed on 14 September 2017)]; Available online: http://www.fpharm.uniba.sk/en/about-the-faculty/historia.

Hann M.M., Keseru G.M. Finding the sweet spot: The role of nature and nurture in medicinal chemistry. Nat. Rev. Drug Discov. 2012;11:355–365. doi: 10.1038/nrd3701. PubMed DOI

Van de Waterbeemd H., Gifford E. ADMET in-silico modeling: Towards prediction paradise? Nat. Rev. Drug Discov. 2003;2:192–204. doi: 10.1038/nrd1032. PubMed DOI

Bak A., Magdziarz T., Polanski J. Pharmacophore-based database mining for probing fragmental drug-likeness of diketo acid analogues. SAR QSAR Environ. Res. 2012;23:185–204. doi: 10.1080/1062936X.2011.645875. PubMed DOI

Stanton D.T. QSAR and QSPR model interpretation using partial least squares (PLS) analysis. Curr. Comput. Aided Drug Des. 2012;8:107–127. doi: 10.2174/157340912800492357. PubMed DOI

Polanski J., Bak A., Gieleciak R., Magdziarz T. Modeling robust QSAR. J. Chem. Inf. Model. 2006;46:2310–2318. doi: 10.1021/ci050314b. PubMed DOI

Bak A., Polanski J. The 4D-QSAR study on anti-HIV HEPT analogues. Bioorg. Med. Chem. 2006;14:273–279. doi: 10.1016/j.bmc.2005.08.023. PubMed DOI

Bak A., Polanski J. Modeling robust QSAR 3: SOM-4D-QSAR with iterative variable elimination IVE-PLS: Application to steroid, azo dye, and benzoic acid series. J. Chem. Inf. Model. 2007;47:1469–1480. doi: 10.1021/ci700025m. PubMed DOI

Bak A., Kozik V., Smolinski A., Jampilek J. Multidimensional (3D/4D-QSAR) probability-guided pharmacophore mapping: Investigation of activity profile for a series of drug absorption promoters. RSC Adv. 2016;6:76183–76205. doi: 10.1039/C6RA15820J. DOI

Bak A., Wyszomirski M., Magdziarz T., Smolinski A., Polanski J. Structure-based modeling of dye-fiber affinity with SOM paradigm: Application to set of antraquinone derivatives. Comb. Chem. High Throughput Screen. 2014;17:485–502. doi: 10.2174/1386207317666140205195252. PubMed DOI

Bak A., Daszykowski M., Kaminski Z., Kiec-Kononowicz K., Kuder K., Fraczyk J., Kolesinska B., Ciosek P., Polanski J. Probing an artificial polypeptide receptor library using a series of novel histaminę H3 receptor ligands. Comb. Chem. High Throughput Screen. 2014;17:146–156. doi: 10.2174/13862073113169990054. PubMed DOI

Bak A., Kozik V., Smolinski A., Jampilek J. In-silico estimation of basic-activity relevant parameters for a set of drug absorption promoters. SAR QSAR Environ. Res. 2017;6:427–449. doi: 10.1080/1062936X.2017.1327459. PubMed DOI

Kubinyi H. Hansch Analysis and Related Approaches. Wiley-VCH Verlag GmbH; Weinheim, Germany: 1993.

Loenarz C., Schofield C.J. Physiological and biochemical aspects of hydroxylations and demethylations catalyzed by human 2-oxoglutarate oxygenases. Trends Biochem. Sci. 2011;36:7–18. doi: 10.1016/j.tibs.2010.07.002. PubMed DOI

Lavaissiere L., Jia S., Nishiyama M., de la Monte S., Stern A.M., Wands J.R., Friedman P.A. Overexpression of human aspartyl(asparaginyl)beta-hydroxylase in hepatocellular carcinoma and cholangiocarcinoma. J. Clin. Investig. 1996;98:1313–1323. doi: 10.1172/JCI118918. PubMed DOI PMC

Aihara A., Huang C.K., Olsen M.J., Lin Q., Chung W., Tang Q., Dong X., Wands J.R. A cell-surface beta-hydroxylase is a biomarker and therapeutic target for hepatocellular carcinoma. Hepatology. 2014;60:1302–1313. doi: 10.1002/hep.27275. PubMed DOI PMC

Jang M.S., Zlobin A., Kast W.M., Miele L. Notch signalling as a target in multimodality cancer therapy. Curr. Opin. Mol. Ther. 2000;2:55–65. PubMed

Iwagami Y., Huang C.K., Olsen M.J., Thomas J.M., Jang G., Kim M., Lin Q., Carlson R.I., Wagner C.E., Dong X., et al. Aspartate beta-hydroxylase modulates cellular senescence through glycogen synthase kinase 3beta in hepatocellular carcinoma. Hepatology. 2016;63:1213–1226. doi: 10.1002/hep.28411. PubMed DOI PMC

Kumar R., Juillerat-Jeanneret L., Golshayan D. Notch antagonists: Potential modulators of cancer and inflammatory diseases. J. Med. Chem. 2016;59:7719–7737. doi: 10.1021/acs.jmedchem.5b01516. PubMed DOI

Takebe N., Nguyen D., Yang S.X. Targeting notch signalling pathway in cancer: Clinical development advances and challenges. Pharmacol. Ther. 2014;141:140–149. doi: 10.1016/j.pharmthera.2013.09.005. PubMed DOI PMC

Newman D.J., Cragg G.M. Natural products as sources of new drugs from 1981 to 2014. J. Nat. Prod. 2016;79:629–661. doi: 10.1021/acs.jnatprod.5b01055. PubMed DOI

Altmann K.H., Gertsch J. Anticancer drugs from nature-natural products as a unique source of new microtubule-stabilizing agents. Nat. Prod. Rep. 2007;24:327–357. doi: 10.1039/B515619J. PubMed DOI

Newman D.J., Cragg G.M. Natural products as sources of new drugs over the last 25 years. J. Nat. Prod. 2007;70:461–477. doi: 10.1021/np068054v. PubMed DOI

Kris M.G., O’Connell J.P., Gralla R.J., Wertheim M.S., Parente R.M., Schiff P.B., Young C.W. Phase I trial of taxol given as a 3-hour infusion every 21 days. Cancer Treat. Rep. 1986;70:605–607. doi: 10.1016/0378-8741(86)90014-0. PubMed DOI

Van Bockxmeer F.M., Martin C.E., Thompson D.E., Constable I.J. Taxol for the treatment of proliferative vitreoretinopathy. Investig. Ophthalmol. Vis. Sci. 1985;26:1140–1147. PubMed

Tabaczar S., Koceva-Chyla A., Matczak K., Gwozdzinski K. Molecular mechanisms of antitumour activity of taxanes. I. Interaction of docetaxel with microtubules. Postepy Hig. Med. Dosw. 2010;64:568–681. PubMed

Wang B.C., Yang J.J., Luo D.L., Qiao H.X., Xie Z., Zhang X.C., Wu Y.L. Complete remission and fatal interstitial pneumonitis related to nab-paclitaxel in refractory small cell lung cancer: A case report and review of the literature. Thorac. Cancer. 2012;3:84–87. doi: 10.1111/j.1759-7714.2011.00086.x. PubMed DOI

Wieczorek A., Blauz A., Zal A., Arabshahi H.J., Reynisson J., Hartinger C.G., Rychlik B., Plazuk D. Ferrocenyl paclitaxel and docetaxel derivatives: Impact of an organometallic moiety on the mode of action of Taxanes. Chem. Eur. J. 2016;22:11413–11421. doi: 10.1002/chem.201601809. PubMed DOI

Zhang S.H., Liu G.F., Li X.F., Liu L., Yu S.N. Efficacy of different chemotherapy regimens in treatment of advanced or metastatic pancreatic cancer: A network meta-analysis. J. Cell. Physiol. 2017 doi: 10.1002/jcp.26183. in press. PubMed DOI

De Caen A.R., Berg M.D., Chameides L., Gooden C.K., Hickey R.W., Scott H.F., Sutton R.M., Tijssen J.A., Topjian A., van der Jagt E.W., et al. Part 12: Pediatric advanced life support: 2015 American Heart Association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2015;132:S526–S542. doi: 10.1161/CIR.0000000000000266. PubMed DOI PMC

Ottaggio L., Bestoso F., Armirotti A., Balbi A., Damonte G., Mazzei M., Sancandi M., Miele M. Taxanes from shells and leaves of Corylus avellana. J. Nat. Prod. 2008;71:58–60. doi: 10.1021/np0704046. PubMed DOI

Chen Y.R., Li P.C., Yang S., Tong N.N., Zhang J., Zhao X.Y. Tetrandrine enhances the anticancer effects of arsenic trioxide in vitro. Int. J. Clin. Pharmacol. Ther. 2014;52:416–424. doi: 10.5414/CP201939. PubMed DOI

Shen Y.C., Chou C.J., Chiou W.F., Chen C.F. Anti-inflammatory effects of the partially purified extract of radix Stephaniae tetrandrae: Comparative studies of its active principles tetrandrine and fangchinoline on human polymorphonuclear leukocyte functions. Mol. Pharmacol. 2001;60:1083–1090. PubMed

Yang Z., Concannon J., Ng K.S., Seyb K., Mortensen L.J., Ranganath S., Gu F., Levy O., Tong Z., Martyn K., et al. Tetrandrine identified in a small molecule screen to activate mesenchymal stem cells for enhanced immunomodulation. Sci. Rep. 2016;6:30263. doi: 10.1038/srep30263. PubMed DOI PMC

Zhang L.J., Geng Y.L., Duan W.J., Wang D.J., Fu M.R., Wang X. Ionic liquid-based ultrasound-assisted extraction of fangchinoline and tetrandrine from Stephaniae tetrandrae. J. Sep. Sci. 2009;32:3550–3554. doi: 10.1002/jssc.200900413. PubMed DOI

Wang N., Pan W.D., Zhu M.F., Zhang M.S., Hao X.J., Liang G.Y., Feng Y.B. Fangchinoline induces autophagic cell death via p53/sestrin2/AMPK signalling in human hepatocellular carcinoma cells. Br. J. Pharmacol. 2011;164:731–742. doi: 10.1111/j.1476-5381.2011.01349.x. PubMed DOI PMC

Ma Z.Z., Hano Y., Nomura T., Chen Y.J. Two new pyrroloquinazolinoquinoline alkaloids from Peganum nigellastrum. Heterocycles. 1997;46:541–546.

Du W. Towards new anticancer drugs: A decade of advances in synthesis of camptothecins and related alkaloids. Tetrahedron. 2003;59:8649–8687. doi: 10.1016/S0040-4020(03)01203-1. DOI

Pizzolato J.F., Saltz L.B. The camptothecins. Lancet. 2003;361:2235–2242. doi: 10.1016/S0140-6736(03)13780-4. PubMed DOI

Liang J.L., Cha H.C., Jahng Y. Recent advances in the studies on luotonins. Molecules. 2011;16:4861–4883. doi: 10.3390/molecules16064861. PubMed DOI PMC

Haider N., Nuß S. Weinreb amidation as the cornerstone of an improved synthetic route to A-ring-modified derivatives of luotonin A. Molecules. 2012;17:11363–11378. doi: 10.3390/molecules171011363. PubMed DOI PMC

Haider N., Meng G.N., Roger S., Wank S. An efficient and selective access to 1-substituted and 3-substituted derivatives of luotonin A. Tetrahedron. 2013;69:7066–7072. doi: 10.1016/j.tet.2013.06.040. DOI

Zhou H.B., Liu G.S., Yao Z.J. Short and efficient total synthesis of luotonin A and 22-hydroxyacuminatine using a common cascade strategy. J. Org. Chem. 2007;72:6270–6272. doi: 10.1021/jo070837d. PubMed DOI

Atia M., Bogdan D., Brugger M., Haider N., Matyus P. Remarkable regioselectivities in the course of the synthesis of two new luotonin A derivatives. Tetrahedron. 2017;73:3231–3239. doi: 10.1016/j.tet.2017.04.052. DOI

Ibric A., Dutter K., Marian B., Haider N. A facile oxidative opening of the C-ring in luotonin A and derivatives. Molecules. 2017;22:1540. doi: 10.3390/molecules22091540. PubMed DOI PMC

Kruse J.P., Gu W. Modes of p53 regulation. Cell. 2009;137:609–622. doi: 10.1016/j.cell.2009.04.050. PubMed DOI PMC

Vaseva A.V., Moll U.M. The mitochondrial p53 pathway. Biochim. Biophys. Acta. 2009;1787:414–420. doi: 10.1016/j.bbabio.2008.10.005. PubMed DOI PMC

Haupt S. Apoptosis—The p53 network. J. Cell Sci. 2003;116:4077–4085. doi: 10.1242/jcs.00739. PubMed DOI

Muller P.A.J., Vousden K.H. P53 Mutations in cancer. Nat. Cell Biol. 2013;15:2–8. doi: 10.1038/ncb2641. PubMed DOI

Olivier M., Hollstein M., Hainaut P. TP53 mutations in human cancers: Origins, consequences, and clinical use. Cold Spring Harb. Perspect. Biol. 2010;2:a001008. doi: 10.1101/cshperspect.a001008. PubMed DOI PMC

Koonin E.V., Rogozin I.B., Glazko G.V. p53 Gain-of-Function. Cell Cycle. 2005;4:686–688. doi: 10.4161/cc.4.5.1691. PubMed DOI

Duffy M.J., Synnott N.C., McGowan P.M., Crown J., O’Connor D., Gallagher W.M. P53 as a target for the treatment of cancer. Cancer Treat. Rev. 2014;40:1153–1160. doi: 10.1016/j.ctrv.2014.10.004. PubMed DOI

Khoo K.H., Hoe K.K., Verma C.S., Lane D.P. Drugging the p53 pathway: Understanding the route to clinical efficacy. Nat. Rev. Drug Discov. 2014;13:217–236. doi: 10.1038/nrd4288. PubMed DOI

Takimoto R., Wang W., Dicker D.T., Rastinejad F., Lyssikatos J., el-Deiry W.S. The mutant p53-conformation modifying drug, CP-31398, can induce apoptosis of human cancer cells and can stabilize wild-type p53 protein. Cancer Biol. Ther. 2002;1:47–55. doi: 10.4161/cbt.1.1.41. PubMed DOI

Xu J., Timares L., Heilpern C., Weng Z., Li C., Xu H., Pressey J.G., Elmets C., Kopelovich L., Athar M. Targeting wild-type and mutant p53 with small molecule CP-31398 blocks the growth of rhabdomyosarcoma by inducing reactive oxygen species-dependent apoptosis. Cancer Res. 2010;70:6566–6576. doi: 10.1158/0008-5472.CAN-10-0942. PubMed DOI PMC

Musiol R., Jampilek J., Buchta V., Silva L., Niedbala H., Podeszwa B., Palka A., Majerz-Maniecka K., Oleksyn B., Polanski J. Antifungal properties of new series of quinoline derivatives. Bioorg. Med. Chem. 2006;14:3592–3598. doi: 10.1016/j.bmc.2006.01.016. PubMed DOI

Cieslik W., Musiol R., Nycz J.E., Jampilek J., Vejsova M., Wolff M., Machura B., Polanski J. Contribution to investigation of antimicrobial activity of styrylquinolines. Bioorg. Med. Chem. 2012;20:6960–6968. doi: 10.1016/j.bmc.2012.10.027. PubMed DOI

Musiol R., Tabak D., Niedbala H., Podeszwa B., Jampilek J., Kralova K., Dohnal J., Finster J., Mencel A., Polanski J. Investigating biological activity spectrum for novel quinoline analogues 2: Hydroxyquinolinecarboxamides with photosynthesis-inhibiting activity. Bioorg. Med. Chem. 2008;16:4490–4499. doi: 10.1016/j.bmc.2008.02.065. PubMed DOI

Musiol R., Jampilek J., Nycz J.E., Pesko M., Carroll J., Kralova K., Vejsova M., O’Mahony J., Coffey A., Mrozek A., et al. Investigating the activity spectrum for ring-substituted 8-hydroxyquinolines. Molecules. 2010;15:288–304. doi: 10.3390/molecules15010288. PubMed DOI PMC

Jampilek J., Musiol R., Pesko M., Kralova K., Vejsova M., Carroll J., Coffey A., Finster J., Tabak D., Niedbala H., et al. Ring-substituted 4-hydroxy-1H-quinolin-2-ones: Preparation and biological activity. Molecules. 2009;14:1145–1159. doi: 10.3390/molecules14031145. PubMed DOI PMC

Cieslik W., Spaczynska E., Malarz K., Tabak D., Nevin E., O’Mahony J., Coffey A., Mrozek-Wilczkiewicz A., Jampilek J., Musiol R. Investigation of the antimycobacterial activity of 8-hydroxyquinolines. Med. Chem. 2015;11:771–779. doi: 10.2174/1573406410666150807111703. PubMed DOI

Polanski J., Niedbala H., Musiol R., Podeszwa B., Tabak D., Palka A., Mencel A., Mouscadet J.F., Le Bret M. Fragment based approach for the investigation of HIV-1 integrase inhibition. Lett. Drug Des. Discov. 2007;4:99–105. doi: 10.2174/157018007779422532. DOI

Polanski J., Niedbala H., Musiol R., Podeszwa B., Tabak D., Palka A., Mencel A., Finster J., Mouscadet J.F., Bret M.L. 5-Hydroxy-6-quinaldic acid as a novel molecular scaffold for HIV-1 integrase inhibitors. Lett. Drug Des. Discov. 2006;3:175–178. doi: 10.2174/157018006776286934. DOI

Kurczyk A., Warszycki D., Musiol R., Kafel R., Bojarski A.J., Polanski J. Ligand-based virtual screening in a search for novel anti-HIV-1 chemotypes. J. Chem. Inf. Model. 2015;55:2168–2177. doi: 10.1021/acs.jcim.5b00295. PubMed DOI

Podeszwa B., Niedbala H., Polanski J., Musiol R., Tabak D., Finster J., Serafin K., Milczarek M., Wietrzyk J., Boryczka S., et al. Investigating the antiproliferative activity of quinoline-5,8-diones and styrylquinolinecarboxylic acids on tumour cell lines. Bioorg. Med. Chem. Lett. 2007;17:6138–6141. doi: 10.1016/j.bmcl.2007.09.040. PubMed DOI

Serda M., Kalinowski D.S., Mrozek-Wilczkiewicz A., Musiol R., Szurko A., Ratuszna A., Pantarat N., Kovacevic Z., Merlot A.M., Richardson D.R., et al. Synthesis and characterization of quinoline-based thiosemicarbazones and correlation of cellular iron-binding efficacy to anti-tumour efficacy. Bioorg. Med. Chem. Lett. 2012;22:5527–5531. doi: 10.1016/j.bmcl.2012.07.030. PubMed DOI

Serda M., Kalinowski D.S., Rasko N., Potuckova E., Mrozek-Wilczkiewicz A., Musiol R., Malecki J.G., Sajewicz M., Ratuszna A., Muchowicz A., et al. Exploring the anti-cancer activity of novel thiosemicarbazones generated through the combination of retro-fragments: Dissection of critical structure-activity relationships. PLoS ONE. 2014;9:e110291. doi: 10.1371/journal.pone.0110291. PubMed DOI PMC

Mrozek-Wilczkiewicz A., Serda M., Musiol R., Malecki G., Szurko A., Muchowicz A., Golab J., Ratuszna A., Polanski J. Iron chelators in photodynamic therapy revisited: Synergistic effect by novel highly active thiosemicarbazones. ACS Med. Chem. Lett. 2014;5:336–339. doi: 10.1021/ml400422a. PubMed DOI PMC

Pastuch-Gawolek G., Malarz K., Mrozek-Wilczkiewicz A., Musiol M., Serda M., Czaplinska B., Musiol R. Small molecule glycoconjugates with anticancer activity. Eur. J. Med. Chem. 2016;112:130–144. doi: 10.1016/j.ejmech.2016.01.061. PubMed DOI

Mrozek-Wilczkiewicz A., Malarz K., Rams-Baron M., Serda M., Bauer D., Montforts F.P., Ratuszna A., Burley T., Polanski J., Musiol R. Iron chelators and exogenic photosensitizers. Synergy through oxidative stress gene expression. J. Cancer. 2017;8:1979–1987. doi: 10.7150/jca.17959. PubMed DOI PMC

Mrozek-Wilczkiewicz A., Kalinowski D.S., Musiol R., Finster J., Szurko A., Serafin K., Knas M., Kamalapuram S.K., Kovacevic Z., Jampilek J., Ratuszna A., et al. Investigating the anti-proliferative activity of styrylazanaphthalenes and azanaphthalenediones. Bioorg. Med. Chem. 2010;18:2664–2671. doi: 10.1016/j.bmc.2010.02.025. PubMed DOI

Mrozek-Wilczkiewicz A., Spaczynska E., Malarz K., Cieslik W., Rams-Baron M., Krystof V., Musiol R. Design, synthesis and in vitro activity of anticancer styrylquinolines. The p53 independent mechanism of action. PLoS ONE. 2015;10:e0142678. doi: 10.1371/journal.pone.0142678. PubMed DOI PMC

Barry N.P.E., Sadler P.J. Exploration of the medical periodic table: Towards new targets. Chem. Commun. 2013;49:5106–5131. doi: 10.1039/c3cc41143e. PubMed DOI

Azuara L.R. Copper Amino Acidate Diimine Nitrate Compounds and Their Methyl Derivatives and a Process for Preparing Them. 5,576,326. US Patent. 1996 Nov 19;

Serment-Guerrero J., Bravo-Gomez M.E., Lara-Rivera E., Ruiz-Azuara L. Genotoxic assessment of the copper chelated compounds Casiopeinas: Clues about their mechanisms of action. J. Inorg. Biochem. 2017;166:68–75. doi: 10.1016/j.jinorgbio.2016.11.007. PubMed DOI

Krikavova R., Vanco J., Travnicek Z., Hutyra J., Dvorak Z. Design and characterization of highly in vitro antitumour active ternary copper(II) complexes containing 2′-hydroxychalcone ligands. J. Inorg. Biochem. 2016;163:8–17. doi: 10.1016/j.jinorgbio.2016.07.005. PubMed DOI

Krikavova R., Vanco J., Travnicek Z., Buchtík R., Dvorak Z. Copper(II) quinolinonato-7-carboxamido complexes as potent antitumour agents with broad spectra and selective effects. RSC Adv. 2016;6:3899–3909. doi: 10.1039/C5RA22141B. DOI

Travnicek Z., Vanco J., Buchtík R., Dvorak Z. Utilization of Copper Complexes Involving 2-Phenyl-3-Hydroxy-4(1H)-Quinolinone and 1,10-Phenanthroline Derivatives for the Preparation of Drugs for the Treatment of Tumour Diseases. EP2650000 B1. EU Patent. 2017 Mar 15;

Travnicek Z., Vanco J., Hutyra J., Krikavova R., Dvorak Z. Complexes of Copper with Derivatives (E)-1-(2′-Hydroxyphenyl)-3-phenyl-prop-2-en-1-one and Their Use as Pharmaceuticals in the Antitumour Therapy. Application PV-2015-598. Czech Patent. 2015 Sep 2;

Cerella C., Gaigneaux A., Mazumder A., Lee J.Y., Saland E., Radogna F., Farge T., Vergez F., Recher C., Sarry J.E., et al. Bcl-2 protein family expression pattern determines synergistic pro-apoptotic effects of BH3 mimetics with hemisynthetic cardiac glycoside UNBS1450 in acute myeloid leukemia. Leukemia. 2017;31:755–759. doi: 10.1038/leu.2016.341. PubMed DOI PMC

Vanden Berghe T., Linkermann A., Jouan-Lanhouet S., Walczak H., Vandenabeele P. Regulated necrosis: The expanding network of non-apoptotic cell death pathways. Nat. Rev. Mol. Cell Biol. 2014;15:135–147. doi: 10.1038/nrm3737. PubMed DOI

Lockshin R.A., Williams C.M. Programmed cell death-I. Cytology of degeneration in the intersegmental muscles of the Pernyi silkmoth. J. Insect Physiol. 1965;11:123–133. doi: 10.1016/0022-1910(65)90099-5. PubMed DOI

Diederich M., Cerella C. Non-canonical programmed cell death mechanisms triggered by natural compounds. Semin. Cancer Biol. 2016;40/41:4–34. doi: 10.1016/j.semcancer.2016.06.001. PubMed DOI

Pol J., Vacchelli E., Aranda F., Castoldi F., Eggermont A., Cremer I., Sautes-Fridman C., Fucikova J., Galon J., Spisek R., et al. Trial watch: Immunogenic cell death inducers for anticancer chemotherapy. Oncoimmunology. 2015;4:e1008866. doi: 10.1080/2162402X.2015.1008866. PubMed DOI PMC

World Health Organization Global Tuberculosis Report 2016. [(accessed on 2 September 2017)]; WHO/HTM/TB/2016.13. Available online: http://www.who.int/tb/publications/global_report/en/

Malone L., Schurr A., Lindh H., McKenzie D., Kiser J.S., Williams J.H. The effect of pyrazinamide (aldinamide) on experimental tuberculosis in mice. Am. Rev. Tuberc. 1952;65:511–518. PubMed

Zhang Y., Wade M.M., Scorpio A., Zhang H., Sun Z.H. Mode of action of pyrazinamide: Disruption of Mycobacterium tuberculosis membrane transport and energetics by pyrazinoic acid. J. Antimicrob. Chemother. 2003;52:790–795. doi: 10.1093/jac/dkg446. PubMed DOI

Peterson N.D., Rosen B.C., Dillon N.A., Baughn A.D. Uncoupling environmental pH and intrabacterial acidification from pyrazinamide susceptibility in Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 2015;59:7320–7326. doi: 10.1128/AAC.00967-15. PubMed DOI PMC

Zimhony O., Vilcheze C., Arai M., Welch J.T., Jacobs W.R. Pyrazinoic acid and its n-propyl ester inhibit fatty acid synthase type I in replicating tubercle bacilli. Antimicrob. Agents Chemother. 2007;51:752–754. doi: 10.1128/AAC.01369-06. PubMed DOI PMC

Boshoff H.I., Mizrahi V., Barry C.E. Effects of pyrazinamide on fatty acid synthesis by whole mycobacterial cells and purified fatty acid synthase I. J. Bacteriol. 2002;184:2167–2172. doi: 10.1128/JB.184.8.2167-2172.2002. PubMed DOI PMC

Ngo S.C., Zimhony O., Chung W.J., Sayahi H., Jacobs W.R., Welch J.T. Inhibition of isolated mycobacterium tuberculosis fatty acid synthase I by pyrazinamide analogs. Antimicrob. Agents Chemother. 2007;51:2430–2435. doi: 10.1128/AAC.01458-06. PubMed DOI PMC

Zimhony O., Cox J.S., Welch J.T., Vilcheze C., Jacobs W.R. Pyrazinamide inhibits the eukaryotic-like fatty acid synthetase I (FASI) of Mycobacterium tuberculosis. Nat. Med. 2000;6:1043–1047. PubMed

Sayahi H., Zimhony O., Jacobs W.R., Shekhtman A., Welch J.T. Pyrazinamide, but not pyrazinoic acid, is a competitive inhibitor of NADPH binding to Mycobacterium tuberculosis fatty acid synthase I. Bioorg. Med. Chem. Lett. 2011;21:4804–4807. doi: 10.1016/j.bmcl.2011.06.055. PubMed DOI PMC

Sayahi H., Pugliese K.M., Zimhony O., Jacobs W.R., Shekhtman A., Welch J.T. Analogs of the antituberculous agent pyrazinamide are competitive inhibitors of NADPH binding to M. tuberculosis fatty acid synthase I. Chem. Biodivers. 2012;9:2582–2596. doi: 10.1002/cbdv.201200291. PubMed DOI

Ciccarelli L., Connell S.R., Enderle M., Mills D.J., Vonck J., Grininger M. Structure and conformational variability of the mycobacterium tuberculosis fatty acid synthase multienzyme complex. Structure. 2013;21:1251–1257. doi: 10.1016/j.str.2013.04.023. PubMed DOI

Shi W.L., Zhang X.L., Jiang X., Yuan H.M., Lee J.S., Barry C.E., Wang H.H., Zhang W.H., Zhang Y. Pyrazinamide inhibits trans-translation in Mycobacterium tuberculosis. Science. 2011;333:1630–1632. doi: 10.1126/science.1208813. PubMed DOI PMC

Yang J.J., Liu Y.D., Bi J., Cai Q.X., Liao X.L., Li W.Q., Guo C.Y., Zhang Q., Lin T.W., Zhao Y.F., et al. Structural basis for targeting the ribosomal protein S1 of Mycobacterium tuberculosis by pyrazinamide. Mol. Microbiol. 2015;95:791–803. doi: 10.1111/mmi.12892. PubMed DOI

Shi W.L., Chen J.Z., Feng J., Cui P., Zhang S., Weng X.H., Zhang W.H., Zhang Y. Aspartate decarboxylase (PanD) as a new target of pyrazinamide in Mycobacterium tuberculosis. Emerg. Microbes Infect. 2014;3:e58. doi: 10.1038/emi.2014.61. PubMed DOI PMC

Pandey B., Grover S., Tyagi C., Goyal S., Jamal S., Singh A., Kaur J., Grover A. Molecular principles behind pyrazinamide resistance due to mutations in panD gene in Mycobacterium tuberculosis. Gene. 2016;581:31–42. doi: 10.1016/j.gene.2016.01.024. PubMed DOI

Kim H., Shibayama K., Rimbara E., Mori S. Biochemical characterization of quinolinic acid phosphoribosyltransferase from Mycobacterium tuberculosis H37Rv and inhibition of its activity by pyrazinamide. PLoS ONE. 2014;9:e100062. doi: 10.1371/journal.pone.0100062. PubMed DOI PMC

Servusova B., Paterova P., Mandikova J., Kubicek V., Kucera R., Kunes J., Dolezal M., Zitko J. Alkylamino derivatives of pyrazinamide: Synthesis and antimycobacterial evaluation. Bioorg. Med. Chem. Lett. 2014;24:450–453. doi: 10.1016/j.bmcl.2013.12.054. PubMed DOI

Hopkins P.N. Molecular biology of atherosclerosis. Physiol. Rev. 2013;93:1317–1542. doi: 10.1152/physrev.00004.2012. PubMed DOI

Rohatgi A., Khera A., Berry J.D., Givens E.G., Ayers C.R., Wedin K.E., Neeland I.J., Yuhanna I.S., Rader D.R., de Lemos J.A., et al. HDL cholesterol efflux capacity and incident cardiovascular events. N. Engl. J. Med. 2014;371:2383–2393. doi: 10.1056/NEJMoa1409065. PubMed DOI PMC

Mishra B.B., Tiwari V.K. Natural products: An evolving role in future drug discovery. Eur. J. Med. Chem. 2011;46:4769–47807. doi: 10.1016/j.ejmech.2011.07.057. PubMed DOI

Koehn F.E., Carter G.T. The evolving role of natural products in drug discovery. Nat. Rev. Drug Discov. 2005;4:206–220. doi: 10.1038/nrd1657. PubMed DOI

Waltenberger B., Mocan A., Smejkal K., Heiss E.H., Atanasov A.G. Natural products to counteract the epidemic of cardiovascular and metabolic disorders. Molecules. 2016;21:807. doi: 10.3390/molecules21060807. PubMed DOI PMC

Atanasov A.G., Waltenberger B., Pferschy-Wenzig E.M., Linder T., Wawrosch C., Uhrin P., Temml V., Wang L.M., Schwaiger S., Heiss E.H., et al. Discovery and resupply of pharmacologically active plant-derived natural products: A review. Biotechnol. Adv. 2015;33:1582–1614. doi: 10.1016/j.biotechadv.2015.08.001. PubMed DOI PMC

Jiang Z.M., Sang H.Q., Fu X., Liang Y., Li L. Alpinetin enhances cholesterol efflux and inhibits lipid accumulation in oxidized low-density lipoprotein-loaded human macrophages. Biotechnol. Appl. Biochem. 2015;62:840–847. doi: 10.1002/bab.1328. PubMed DOI

He X.W., Yu D., Li W.L., Zheng Z., Lv C.L., Li C., Liu P., Xu C.Q., Hu X.F., Jin X.P. Anti-atherosclerotic potential of baicalin mediated by promoting cholesterol efflux from macrophages via the PPAR gamma-LXR alpha-ABCA1/ABCG1 pathway. Biomed. Pharmacother. 2016;83:257–264. doi: 10.1016/j.biopha.2016.06.046. PubMed DOI

Wang S., Zhang X., Liu M.Y., Luan H., Ji Y.B., Guo P., Wu C.M. Chrysin inhibits foam cell formation through promoting cholesterol efflux from RAW264.7 macrophages. Pharm. Biol. 2015;53:1481–1487. doi: 10.3109/13880209.2014.986688. PubMed DOI

Iio A., Ohguchi K., Iinuma M., Nozawa Y., Ito M. Hesperetin upregulates ABCA1 expression and promotes cholesterol efflux from THP-1 macrophages. J. Nat. Prod. 2012;75:563–566. doi: 10.1021/np200696r. PubMed DOI

Sun L.Q., Li E., Wang F., Wang T., Qin Z.P., Niu S.H., Qiu C.G. Quercetin increases macrophage cholesterol efflux to inhibit foam cell formation through activating PPAR gamma-ABCA1 pathway. Int. J. Clin. Exp. Pathol. 2015;8:10854–10860. PubMed PMC

Chang Y.C., Lee T.S., Chiang A.N. Quercetin enhances ABCA1 expression and cholesterol efflux through a p38-dependent pathway in macrophages. J. Lipid Res. 2012;53:1840–1850. doi: 10.1194/jlr.M024471. PubMed DOI PMC

Wang L.M., Rotter S., Ladurner A., Heiss E.H., Oberlies N.H., Dirsch V.M., Atanasov A.G. Silymarin constituents enhance ABCA1 expression in THP-1 macrophages. Molecules. 2016;21:55. doi: 10.3390/molecules21010055. PubMed DOI PMC

Rosenblat M., Volkova N., Coleman R., Almagor Y., Aviram M. Antiatherogenicity of extra virgin olive oil and its enrichment with green tea polyphenols in the atherosclerotic apolipoprotein-E-deficient mice: Enhanced macrophage cholesterol efflux. J. Nutr. Biochem. 2008;19:514–523. doi: 10.1016/j.jnutbio.2007.06.007. PubMed DOI

Zhao J.F., Jim Leu S.J., Shyue S.K., Su K.H., Wei J., Lee T.S. Novel effect of paeonol on the formation of foam cells: Promotion of LXRalpha-ABCA1-dependent cholesterol efflux in macrophages. Am. J. Chin. Med. 2013;41:1079–1096. doi: 10.1142/S0192415X13500730. PubMed DOI

Zhao S.J., Li J.K., Wang L.F., Wu X.X. Pomegranate peel polyphenols inhibit lipid accumulation and enhance cholesterol efflux in raw264.7 macrophages. Food Funct. 2016;7:3201–3210. doi: 10.1039/C6FO00347H. PubMed DOI

Zhou W.J., Lin J.C., Chen H.E., Wang J.J., Liu Y., Xia M. Retinoic acid induces macrophage cholesterol efflux and inhibits atherosclerotic plaque formation in apoE-deficient mice. Br. J. Nutr. 2015;114:509–518. doi: 10.1017/S0007114515002159. PubMed DOI

Bechor S., Zolberg Relevy N., Harari A., Almog T., Kamari Y., Ben-Amotz A., Harats D., Shaish A. 9-cis-beta-Carotene increased cholesterol efflux to HDL in macrophages. Nutrients. 2016;8:435. doi: 10.3390/nu8070435. PubMed DOI PMC

Iizuka M., Ayaori M., Uto-Kondo H., Yakushiji E., Takiguchi S., Nakaya K., Hisada T., Sasaki M., Komatsu T., Yogo M., et al. Astaxanthin enhances ATP-binding cassette transporter A1/G1 expressions and cholesterol efflux from macrophages. J. Nutr. Sci. Vitaminol. 2012;58:96–104. doi: 10.3177/jnsv.58.96. PubMed DOI

Kammerer I., Ringseis R., Biemann R., Wen G.P., Eder K. 13-Hydroxy linoleic acid increases expression of the cholesterol transporters ABCA1, ABCG1 and SR-BI and stimulates apoA-I-dependent cholesterol efflux in RAW264.7 macrophages. Lipids Health Dis. 2011;10:222. doi: 10.1186/1476-511X-10-222. PubMed DOI PMC

Shao F., Ford D.A. Differential regulation of ABCA1 and macrophage cholesterol efflux by elaidic and oleic acids. Lipids. 2013;48:757–767. doi: 10.1007/s11745-013-3808-0. PubMed DOI PMC

Dong S.Z., Zhao S.P., Wu Z.H., Yang J., Xie X.Z., Yu B.L., Nie S. Curcumin promotes cholesterol efflux from adipocytes related to PPARgamma-LXRalpha-ABCA1 passway. Mol. Cell. Biochem. 2011;358:281–285. doi: 10.1007/s11010-011-0978-z. PubMed DOI

Liu T.R., Li C., Sun H.G., Luo T.T., Tan Y., Tian D., Guo Z.G. Curcumin inhibits monocyte chemoattractant protein-1 expression and enhances cholesterol efflux by suppressing the c-Jun N-terminal kinase pathway in macrophage. Inflamm. Res. 2014;63:841–850. doi: 10.1007/s00011-014-0758-9. PubMed DOI

Lin X.L., Liu M.H., Hu H.J., Feng H.R., Fan X.J., Zou W.W., Pan Y.Q., Hu X.M., Wang Z. Curcumin enhanced cholesterol efflux by upregulating ABCA1 expression through AMPK-SIRT1-LXR alpha signalling in THP-1 macrophage-derived foam cells. DNA Cell Biol. 2015;34:561–572. doi: 10.1089/dna.2015.2866. PubMed DOI

Liu X., Kunert O., Blunder M., Fakhrudin N., Noha S.M., Malainer C., Schinkovitz A., Heiss E.H., Atanasov A.G., Kollroser M., et al. Polyyne hybrid compounds from Notopterygium incisum with peroxisome proliferator-activated receptor gamma agonistic effects. J. Nat. Prod. 2014;77:2513–2521. doi: 10.1021/np500605v. PubMed DOI PMC

Atanasov A.G., Blunder M., Fakhrudin N., Liu X., Noha S.M., Malainer C., Kramer M.P., Cocic A., Kunert O., Schinkovitz A., et al. Polyacetylenes from Notopterygium incisum—New selective partial agonists of peroxisome proliferator-activated receptor-gamma. PLoS ONE. 2013;8:e61755. doi: 10.1371/journal.pone.0061755. PubMed DOI PMC

Wang L., Palme V., Schilcher N., Ladurner A., Heiss E.H., Stangl H., Bauer R., Dirsch V.M., Atanasov A.G. The dietary constituent falcarindiol promotes cholesterol efflux from THP-1 macrophages by increasing ABCA1 gene transcription and protein stability. Front. Pharmacol. 2017;8:596. doi: 10.3389/fphar.2017.00596. PubMed DOI PMC

Gao H., Li L.Y., Li L., Gong B., Dong P.Z., Fordjour P.A., Zhu Y., Fan G.W. Danshensu promotes cholesterol efflux in RAW264.7 macrophages. Lipids. 2016;51:1083–1092. doi: 10.1007/s11745-016-4178-1. PubMed DOI

Lv Y.C., Yang J., Yao F., Xie W., Tang Y.Y., Ouyang X.P., He P.P., Tan Y.L., Li L., Zhang M., et al. Diosgenin inhibits atherosclerosis via suppressing the MiR-19b-induced downregulation of ATP-binding cassette transporter A1. Atherosclerosis. 2015;240:80–89. doi: 10.1016/j.atherosclerosis.2015.02.044. PubMed DOI

Yue J.M., Li B., Jing Q.P., Guan Q.B. Salvianolic acid B accelerated ABCA1-dependent cholesterol efflux by targeting PPAR-gamma and LXR alpha. Biochem. Biophys. Res. Commun. 2015;462:233–238. doi: 10.1016/j.bbrc.2015.04.122. PubMed DOI

Xu X.L., Li Q., Pang L.W., Huang G.Q., Huang J.C., Shi M., Sun X.T., Wang Y.Q. Arctigenin promotes cholesterol efflux from THP-1 macrophages through PPAR-gamma/LXR-alpha signalling pathway. Biochem. Biophys. Res. Commun. 2013;441:321–326. doi: 10.1016/j.bbrc.2013.10.050. PubMed DOI

Uto-Kondo H., Ayaori M., Nakaya K., Takiguchi S., Yakushiji E., Ogura M., Terao Y., Ozasa H., Sasaki M., Komatsu T., et al. Citrulline increases cholesterol efflux from macrophages in vitro and ex vivo via ATP-binding cassette transporters. J. Clin. Biochem. Nutr. 2014;55:32–39. doi: 10.3164/jcbn.13-76. PubMed DOI PMC

Fu X., Xu A.G., Yao M.Y., Guo L., Zhao L.S. Emodin enhances cholesterol efflux by activating peroxisome proliferator-activated receptor-gamma in oxidized low density lipoprotein-loaded THP1 macrophages. Clin. Exp. Pharmacol. Physiol. 2014;41:679–684. PubMed

Wang L.M., Wesemann S., Krenn L., Ladurner A., Heiss E.H., Dirsch V.M., Atanasov A.G. Erythrodiol, an olive oil constituent, increases the half-life of ABCA1 and enhances cholesterol efflux from THP-1-derived macrophages. Front. Pharmacol. 2017;8:375. doi: 10.3389/fphar.2017.00375. PubMed DOI PMC

Wang L., Ladurner A., Latkolik S., Schwaiger S., Linder T., Hosek J., Palme V., Schilcher N., Polansky O., Heiss E.H., et al. Leoligin, the major lignan from edelweiss (Leontopodium nivale subsp. alpinum), promotes cholesterol efflux from THP-1 macrophages. J. Nat. Prod. 2016;79:1651–1657. PubMed PMC

Wang L., Palme V., Rotter S., Schilcher N., Cukaj M., Wang D., Ladurner A., Heiss E.H., Stangl H., Dirsch V.M., et al. Piperine inhibits ABCA1 degradation and promotes cholesterol efflux from THP-1-derived macrophages. Mol. Nutr. Food Res. 2017;61:1500960. doi: 10.1002/mnfr.201500960. PubMed DOI PMC

Li C.H., Gong D., Chen L.Y., Zhang M., Xia X.D., Cheng H.P., Huang C., Zhao Z.W., Zheng X.L., Tang X.E., et al. Puerarin promotes ABCA1-mediated cholesterol efflux and decreases cellular lipid accumulation in THP-1 macrophages. Eur. J. Pharmacol. 2017;811:74–86. doi: 10.1016/j.ejphar.2017.05.055. PubMed DOI

Wu C.M., Chen R., Liu M.Y., Liu D., Li X., Wang S., Niu S.W., Guo P., Lin W.H. Spiromastixones inhibit foam cell formation via regulation of cholesterol efflux and uptake in RAW264.7 macrophages. Mar. Drugs. 2015;13:6352–6365. doi: 10.3390/md13106352. PubMed DOI PMC

Yin K., You Y., Swier V., Tang L., Radwan M.M., Pandya A.N., Agrawal D.K. Vitamin D protects against atherosclerosis via regulation of cholesterol efflux and macrophage polarization in hypercholesterolemic swine. Arterioscler. Thromb. Vasc. Biol. 2015;35:2432–2442. doi: 10.1161/ATVBAHA.115.306132. PubMed DOI PMC

Majdalawieh A.F., Ro H.S. Sesamol and sesame (Sesamum indicum) oil enhance macrophage cholesterol efflux via up-regulation of PPAR gamma 1 and LXR alpha transcriptional activity in a MAPK-dependent manner. Eur. J. Nutr. 2015;54:691–700. doi: 10.1007/s00394-014-0747-3. PubMed DOI

Liu N., Wu C.M., Sun L.Z., Zheng J., Guo P. Sesamin enhances cholesterol efflux in RAW264.7 macrophages. Molecules. 2014;19:7516–7527. doi: 10.3390/molecules19067516. PubMed DOI PMC

Majdalawieh A.F., Ro H.S. The anti-atherogenic properties of sesamin are mediated via improved macrophage cholesterol efflux through PPAR gamma 1-LXR alpha and MAPK signalling. Int. J. Vitam. Nutr. Res. 2014;84:79–91. doi: 10.1024/0300-9831/a000195. PubMed DOI

Wang H., Liu Y., Zhu L., Wang W.J., Wan Z.F., Chen F.Y., Wu Y., Zhou J., Yuan Z.Y. 17-beta-Estradiol promotes cholesterol efflux from vascular smooth muscle cells through a liver X receptor alpha-dependent pathway. Int. J. Mol. Med. 2014;33:550–558. PubMed

Wang D.D., Tosevska A., Heiss E.H., Ladurner A., Molzer C., Wallner M., Bulmer A., Wagner K.H., Dirsch V.M., Atanasov A.G. Bilirubin decreases macrophage cholesterol efflux and ATP-binding cassette transporter A1 protein expression. J. Am. Heart Assoc. 2017;6:e005520. doi: 10.1161/JAHA.117.005520. PubMed DOI PMC

Zhang H.M., Li X.Y., Qian Z.J. Regulation of macrophage cholesterol efflux and liver X receptor a activation by nicotine. Int. J. Clin. Exp. Med. 2015;8:16374–16378. PubMed PMC

Karran E., Mercken M., De Strooper B. The amyloid cascade hypothesis for Alzheimer’s disease: An appraisal for the development of therapeutics. Nat. Rev. Drug Discov. 2011;10:698–712. doi: 10.1038/nrd3505. PubMed DOI

Hughes E.R., Nikolic K., Ramsay R.R. One for All? Hitting multiple Alzheimer’s Ddisease targets with one drug. Front. Neurosci. 2016;10:177. doi: 10.3389/fnins.2016.00177. PubMed DOI PMC

Nikolic K., Mavridis L., Djikic T., Vucicevic J., Agbaba D., Yelekci K., Mitchell J.B.O. Drug design for CNS diseases: Polypharmacological profiling of compounds using chemoinformatic, 3D-QSAR and virtual screening methodologies. Front. Neurosci. 2016;10:265. doi: 10.3389/fnins.2016.00265. PubMed DOI PMC

Wang L., Ma C., Wipf P., Liu H., Su W., Xie X.Q. Target hunter: An in-silico target identification tool for predicting therapeutic potential of small organic molecules based on chemogenomic database. AAPS J. 2013;15:395–406. doi: 10.1208/s12248-012-9449-z. PubMed DOI PMC

Bautista-Aguilera O.M., Esteban G., Bolea I., Nikolic K., Agbaba D., Moraleda I., Iriepa I., Samadi A., Soriano E., Unzeta M., et al. Design, synthesis, pharmacological evaluation, QSAR analysis, molecular modelling and ADMET of novel donepezil-indolyl hybrids as multipotent cholinesterase/monoamine oxidase inhibitors for the potential treatment of Alzheimer’s disease. Eur. J. Med. Chem. 2014;75:82–95. doi: 10.1016/j.ejmech.2013.12.028. PubMed DOI

Bautista-Aguilera O.M., Samadi A., Chioua M., Nikolic K., Filipic S., Agbaba D., Soriano E., de Andres L., Rodriguez-Franco M.I., Alcaro S., et al. N-Methyl-N-((1-methyl-5-(3-(1-(2-methylbenzyl)-piperidin-4-yl)propoxy)-1H-indol-2-yl)methyl)prop-2-yn-1-amine, a new cholinesterase and monoamine oxidase dual. J. Med. Chem. 2014;57:10455–10463. doi: 10.1021/jm501501a. PubMed DOI

Bolea I., Juarez-Jimenez J., de los Rios C., Chioua M., Pouplana R., Luque F.J., Unzeta M., Marco-Contelles J., Samadi A. Synthesis, biological evaluation, and molecular modelling of donepezil and N-(5-(Benzyloxy)-1-methyl-1H-indol-2-yl)methyl-N-methylprop-2-yn-1-amine hybrids as new multipotent cholinesterase/monoamine oxidase inhibitors for the treatment of Alzheimer’s disease. J. Med. Chem. 2011;54:8251–8270. PubMed

Nikolic K., Mavridis L., Bautista-Aguilera O.M., Marco-Contelles J., Stark H., Carmo Carreiras M., Rossi I., Massarelli P., Agbaba D., Ramsay R.R., et al. Predicting targets of compounds against neurological diseases using cheminformatic methodology. J. Comput. Aided Mol. Des. 2015;29:183–198. doi: 10.1007/s10822-014-9816-1. PubMed DOI

Nikolic K., Agbaba D., Stark H. Pharmacophore modelling, drug design and virtual screening on multi-targeting precognitive agents approaching histaminergic pathways. J. Taiwan Inst. Chem. 2015;46:15–29. doi: 10.1016/j.jtice.2014.09.017. DOI

Jezova D., Herman J.P. Lessons from regular gathering of experts in stress research: Focus on pathophysiological consequences of stress exposure. Stress. 2016;19:339–340. doi: 10.1080/10253890.2016.1213515. PubMed DOI

Jezova D., Hlavacova N. Endocrine factors in stress and psychiatric disorders: Focus on anxiety and salivary steroids. Stress. 2008;1148:495–503. doi: 10.1196/annals.1410.050. PubMed DOI

Prokopova B., Jezova D. Stress and possibilities of its pharmacological modulation—Do we know to measure the stress load? Psychiatr. Praxi. 2013;14:150–154.

Hlavacova N., Wes P.D., Ondrejcakova M., Flynn M.E., Poundstone P.K., Babic S., Murck H., Jezova D. Subchronic treatment with aldosterone induces depression-like behaviours and gene expression changes relevant to major depressive disorder. Int. J. Neuropsychopharmacol. 2012;15:247–265. doi: 10.1017/S1461145711000368. PubMed DOI

Hlavacova N., Solarikova P., Marko M., Brezina I., Jezova D. Blunted cortisol response to psychosocial stress in atopic patients is associated with decreasein salivary alpha-amylase and aldosterone: Focus on sex and menstrual cycle phase. Psychoneuroendocrinology. 2017;78:31–38. doi: 10.1016/j.psyneuen.2017.01.007. PubMed DOI

Segeda V., Izakova L., Hlavacova N., Bednarova A., Jezova D. Aldosterone concentrations in saliva reflect the duration and severity of depressive episode in a sex dependent manner. J. Psychiatr. Res. 2017;91:164–168. doi: 10.1016/j.jpsychires.2017.04.011. PubMed DOI

Sichrovska B., Malik I., Sedlarova E., Csollei J., Muselik J. In vitro antioxidant properties of novel β3-adrenoceptor agonists bearing benzenesulfonamide fragment. Dhaka Univ. J. Pharm. Sci. 2013;12:23–28. doi: 10.3329/dujps.v12i1.16296. DOI

Sichrovska-Havranova L. Ph.D. Thesis. Faculty of Pharmacy, Comenius University in Bratislava; Bratislava, Slovakia: 2014. Preparation, Study of Physico-Chemical Properties and Biological Activity of Compounds with Potential Agonistic Effect on Beta Adrenergic Receptors.

Csanova A., Hlavacova N., Hasiec M., Pokusa M., Prokopova B., Jezova D. β3-Adrenergic receptors, adipokines and neuroendocrine activation during stress induced by repeated immune challenge in male and female rats. Stress. 2017;20:294–302. doi: 10.1080/10253890.2017.1320387. PubMed DOI

Tsopelas F., Giaginis C., Tsantili-Kakoulidou A. Lipophilicity and biomimetic properties to support drug discovery. Exp. Opin. Drug Discov. 2017;12:885–896. doi: 10.1080/17460441.2017.1344210. PubMed DOI

Vrakas D., Giaginis C., Tsantili-Kakoulidou A. Electrostatic interactions and ionization effect in IAM retention. A comparative study with octanol-water partitioning. J. Chromatogr. A. 2008;1187:67–78. doi: 10.1016/j.chroma.2008.01.079. PubMed DOI

Tsopelas F., Vallianatou T., Tsantili-Kakoulidou A. The potential of immobilized artificial membrane chromatography to predict human oral absorption. Eur. J. Pharm. Sci. 2016;81:82–93. doi: 10.1016/j.ejps.2015.09.020. PubMed DOI

De Vrieze M., Janssens P., Szucs R., Van der Eycken J., Lynen F. In vitro prediction of human intestinal absorption and blood-brain barrier partitioning: Development of a lipid analog for micellar liquid chromatography. Anal. Bioanal. Chem. 2015;407:7453–7466. doi: 10.1007/s00216-015-8911-z. PubMed DOI

Chrysanthakopoulos M., Giaginis C., Tsantili-Kakoulidou A. Retention of structurally diverse drugs in human serum albumin chromatography and its potential to simulate plasma protein binding. J. Chromatogr. A. 2010;1217:5761–5768. doi: 10.1016/j.chroma.2010.07.023. PubMed DOI

Chrysanthakopoulos M., Valianatou T., Giaginis C., Tsantili-Kakoulidou A. Investigation of the retention behavior of structurally diverse drugs on alpha1 acid glycoprotein column. Insight on the molecular factors involved and correlation with biological binding data. Eur. J. Pharm. Sci. 2014;60:24–31. doi: 10.1016/j.ejps.2014.04.015. PubMed DOI

Hoppe B., Martens J. Aminosäuren—Bausteine des Lebens. ChiuZ. 1983;17:41–53. doi: 10.1002/ciuz.19830170203. DOI

Hoppe B., Martens J. Aminosäuren—Herstellung und Gewinnung. ChiuZ. 1984;18:73–86. doi: 10.1002/ciuz.19840180302. DOI

Wolman Y., Haverland W.J., Miller S.L. Non-protein amino acids from spark discharges and their comparison with the Murchison meteorite amino acids. Proc. Nat. Acad. Sci. USA. 1972;69:809–811. doi: 10.1073/pnas.69.4.809. PubMed DOI PMC

Schurig V. Exploring chirality in outer space. Anal. Chem. TAS Issue 1215, 2015;35:36–41.

Bada J.L., Protsch R. Racemization reaction of aspartic acid and its use in dating fossil bones. Proc. Nat. Acad. Sci. USA. 1973;70:1331–1334. doi: 10.1073/pnas.70.5.1331. PubMed DOI PMC

Bhushan R., Martens J. Amino Acids. HNB Publishing; New York, NY, USA: 2010. pp. 173–286.

Sajewicz M., Kowalska T. Chiral thin layer chromatography in dynamic studies. A short review. J. Planar Chromatogr. Mod. TLC. 2017;30:333–339. doi: 10.1556/1006.2017.30.5.1. DOI

Sajewicz M., Dolnik M., Kowalska T., Epstein I.R. Condensation dynamics of L-proline and L-hydroxyproline in solution. RSC Adv. 2014;4:7330–7339. doi: 10.1039/C3RA46921B. DOI

Maciejowska A., Godziek A., Talik E., Sajewicz M., Kowalska T., Epstein I.R. Spontaneous pulsation of peptide microstructures in an abiotic liquid system. J. Chromatogr. Sci. 2016;54:1301–1309. doi: 10.1093/chromsci/bmw073. PubMed DOI

Eur. Monitoring Centre for Drugs and Drug Addiction. [(accessed on 1 September 2017)]; Report 2015. Available online: http://www.emcdda.europa.eu/edr2015.

Grasso G., Mielczarek P., Niedziolka M., Silberring J. Metabolism of cryptic peptides derived from neuropeptide FF precursors: The involvement of insulin-degrading enzyme. Int. J. Mol. Sci. 2014;15:16787–16799. doi: 10.3390/ijms150916787. PubMed DOI PMC

Smoluch M., Mielczarek P., Silberring J. Plasma-based ambient ionization mass spectrometry in bioanalytical sciences. Mass Spectrom. Rev. 2016;35:22–34. doi: 10.1002/mas.21460. PubMed DOI

Mielczarek P., Smoluch M., Kotlinska J.H., Labuz K., Gotszalk T., Babij M., Suder P., Silberring J. Electrochemical generation of selegiline metabolites coupled to mass spectrometry. J. Chromatogr. A. 2015;1389:96–103. doi: 10.1016/j.chroma.2015.02.049. PubMed DOI

Rendle D.F. X-ray diffraction in forensic science. Rigaku J. 2003;19:11–22.

Dutrow B., Clark C.M. Geochemical Instrumentation and Analysis: X-ray Powder Diffraction (PXRD) [(accessed on 1 September 2017)]; Available online: https://serc.carleton.edu/research_education/geochemsheets/techniques/XRD.html.

USP Pharmacopeial Convention . General. <941> Characterization of Crystalline and Partially Crystalline Solids by X-ray Powder Diffraction. USP Pharmacopeial Convention; Rockville, MD, USA: 2011.

International Centre for Diffraction Data . PDF-2. ICDD; Newtown Square, PA, USA: 2008.

Rojek B., Wesołowski M. Thermal analysis of selected excipients used in the formulation process of medicinal products. Farm. Przegl. Nauk. 2010;9:45–50.

Szlezak N., Evers M., Wang J., Pérez L. The role of big data and advanced analytics in drug discovery, development, and commercialization. Clin. Pharmacol. Ther. 2014;95:492–495. doi: 10.1038/clpt.2014.29. PubMed DOI

Polanski J. Big data in structure-property studies—From definitions to models. In: Leszczynski J., Roy K., editors. Advances in QSAR Modeling with Applications in Pharmaceutical, Chemical, Food, Agricultural, and Environmental Sciences. Springer; Berlin/Heidelberg, Germany: 2017. pp. 529–552.

Hu Y., Bajorath J. Entering the ‘big data’ era in medicinal chemistry: Molecular promiscuity analysis revisited. Future Sci. OA. 2017;3:FSO179. doi: 10.4155/fsoa-2017-0001. PubMed DOI PMC

Polanski J., Kucia U., Duszkiewicz R., Kurczyk A., Magdziarz T., Gasteiger J. Molecular descriptor data explains market prices of the large commercial chemical compound library. Sci. Rep. 2016;6:28521. doi: 10.1038/srep28521. PubMed DOI PMC

Bickerton G.R., Paolini G.V., Besnard J., Muresan S., Hopkins A.L. Quantifying the chemical beauty of drugs. Nat. Chem. 2012;4:90–98. doi: 10.1038/nchem.1243. PubMed DOI PMC

Hopkins A.L., Keseru G.M., Leeson P.D., Rees D.C., Reynolds C.H. The role of ligand efficiency metrics in drug discovery. Nat. Rev. Drug Discov. 2014;13:105–121. doi: 10.1038/nrd4163. PubMed DOI

Gleeson M.P., Hersey A., Montanari D., Overington J. Probing the links between in vitro potency, ADMET and physicochemical parameters. Nat. Rev. Drug Discov. 2011;10:197–208. doi: 10.1038/nrd3367. PubMed DOI PMC

Swinney D.C., Anthony J. How were new medicines discovered. Nat. Rev. Drug Discov. 2011;10:507–519. doi: 10.1038/nrd3480. PubMed DOI

Overington J.P., Al-Lazikani B., Hopkins A.L. How many drug targets are there? Nat. Rev. Drug Discov. 2006;5:993–996. doi: 10.1038/nrd2199. PubMed DOI

Polanski J., Tkocz A., Kucia U. Beware of ligand efciency (LE): Understanding LE data in modeling structure-activity and structure-economy relationships. J. Chemoinform. 2017;9:49. doi: 10.1186/s13321-017-0236-9. PubMed DOI PMC

Polanski J., Tkocz A. Between descriptors and properties: Understanding the ligand efficiency trends for G protein-coupled receptor and kinase structure-activity data sets. J. Chem. Inf. Model. 2017;26:1321–1329. doi: 10.1021/acs.jcim.7b00116. PubMed DOI

Goracci L., Tortorella S., Tiberi P., Pellegrino R.M., Di Veroli A., Valeri A., Cruciani G. Lipostar, a comprehensive platform-neutral cheminformatics tool for lipidomics. Anal. Chem. 2017;89:6257–6264. doi: 10.1021/acs.analchem.7b01259. PubMed DOI

Polanski J., Gasteiger J. Computer Representation of Chemical Compounds. In: Leszczynski J., Puzyn T., editors. Handbook of Computational Chemistry. Springer; Dordrecht, Germany: 2016. pp. 1–43.