A library of 2,4,6,7-tetrasubstituted-2H-pyrazolo[4,3-c]pyridines was prepared from easily accessible 1-phenyl-3-(2-phenylethynyl)-1H-pyrazole-4-carbaldehyde via an iodine-mediated electrophilic cyclization of intermediate 4-(azidomethyl)-1-phenyl-3-(phenylethynyl)-1H-pyrazoles to 7-iodo-2,6-diphenyl-2H-pyrazolo[4,3-c]pyridines followed by Suzuki cross-couplings with various boronic acids and alkylation reactions. The compounds were evaluated for their antiproliferative activity against K562, MV4-11, and MCF-7 cancer cell lines. The most potent compounds displayed low micromolar GI50 values. 4-(2,6-Diphenyl-2H-pyrazolo[4,3-c]pyridin-7-yl)phenol proved to be the most active, induced poly(ADP-ribose) polymerase 1 (PARP-1) cleavage, activated the initiator enzyme of apoptotic cascade caspase 9, induced a fragmentation of microtubule-associated protein 1-light chain 3 (LC3), and reduced the expression levels of proliferating cell nuclear antigen (PCNA). The obtained results suggest a complex action of 4-(2,6-diphenyl-2H-pyrazolo[4,3-c]pyridin-7-yl)phenol that combines antiproliferative effects with the induction of cell death. Moreover, investigations of the fluorescence properties of the final compounds revealed 7-(4-methoxyphenyl)-2,6-diphenyl-2H-pyrazolo[4,3-c]pyridine as the most potent pH indicator that enables both fluorescence intensity-based and ratiometric pH sensing.

Department of Chemical Biology Palacký University Šlechtitelů 27 CZ 78371 Olomouc Czech Republic

Department of Experimental Biology Palacký University Šlechtitelů 27 CZ 78371 Olomouc Czech Republic

Department of Experimental Physics Faculty of Science Palacký University 17 Listopadu 12 CZ 77146 Olomouc Czech Republic

Department of Organic Chemistry Kaunas University of Technology Radvilėnų pl 19 LT 50254 Kaunas Lithuania

Institute of Molecular and Translational Medicine Faculty of Medicine and Dentistry Palacký University Hněvotínská 5 CZ 77900 Olomouc Czech Republic

Institute of Synthetic Chemistry Kaunas University of Technology K Baršausko g 59 LT 51423 Kaunas Lithuania

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Kumar V., Kaur K., Gupta G.K., Sharma A.K. Pyrazole containing natural products: Synthetic preview and biological significance. Eur. J. Med. Chem. 2013;69:735–753. doi: 10.1016/j.ejmech.2013.08.053. PubMed DOI

Ansari A., Ali A., Asif M. Shamsuzzaman Review: Biologically active pyrazole derivatives. New J. Chem. 2017;41:16–41. doi: 10.1039/C6NJ03181A. DOI

Kucukguzel S.G., Senkardes S. Recent advances in bioactive pyrazoles. Eur. J. Med. Chem. 2015;97:786–815. doi: 10.1016/j.ejmech.2014.11.059. PubMed DOI

Varvuolytė G., Malina L., Bieliauskas A., Hošíková B., Simerská H., Kolářová H., Kleizienė N., Kryštof V., Šačkus A., Žukauskaitė A. Synthesis and photodynamic properties of pyrazole-indole hybrids in the human skin melanoma cell line G361. Dyes Pigment. 2020;183:108666. doi: 10.1016/j.dyepig.2020.108666. DOI

Jayaraj R.L., Elangovan N., Dhanalakshmi C., Manivasagam T., Essa M.M. CNB-001, a novel pyrazole derivative mitigates motor impairments associated with neurodegeneration via suppression of neuroinflammatory and apoptotic response in experimental Parkinson’s disease mice. Chem. Biol. Interact. 2014;220:149–157. doi: 10.1016/j.cbi.2014.06.022. PubMed DOI

Milišiūnaitė V., Kadlecová A., Žukauskaitė A., Doležal K., Strnad M., Voller J., Arbačiauskienė E., Holzer W., Šačkus A. Synthesis and anthelmintic activity of benzopyrano[2,3-c]pyrazol-4(2H)-one derivatives. Mol. Divers. 2020;24:1025–1042. doi: 10.1007/s11030-019-10010-3. PubMed DOI

Horrocks P., Pickard M.R., Parekh H.H., Patel S.P., Pathak R.B. Synthesis and biological evaluation of 3-(4-chlorophenyl)-4-substituted pyrazole derivatives. Org. Biomol. Chem. 2013;11:4891–4898. doi: 10.1039/c3ob27290g. PubMed DOI

Masih A., Agnihotri A.K., Srivastava J.K., Pandey N., Bhat H.R., Singh U.P. Discovery of novel pyrazole derivatives as a potent anti-inflammatory agent in RAW264.7 cells via inhibition of NF-ĸB for possible benefit against SARS-CoV-2. J. Biochem. Mol. Toxicol. 2020;35:e22656. doi: 10.1002/jbt.22656. PubMed DOI PMC

Gogoi P., Shakya A., Ghosh S.K., Gogoi N., Gahtori P., Singh N., Bhattacharyya D.R., Singh U.P., Bhat H.R. In silico study, synthesis, and evaluation of the antimalarial activity of hybrid dimethoxy pyrazole 1,3,5-triazine derivatives. J. Biochem. Mol. Toxicol. 2020;35:e22682. doi: 10.1002/jbt.22682. PubMed DOI

Karrouchi K., Radi S., Ramli Y., Taoufik J., Mabkhot Y.N., Al-Aizari F.A., Ansar M. Synthesis and Pharmacological Activities of Pyrazole Derivatives: A Review. Molecules. 2018;23:134. doi: 10.3390/molecules23010134. PubMed DOI PMC

Khan M.F., Alam M.M., Verma G., Akhtar W., Akhter M., Shaquiquzzaman M. The therapeutic voyage of pyrazole and its analogs: A review. Eur. J. Med. Chem. 2016;120:170–201. doi: 10.1016/j.ejmech.2016.04.077. PubMed DOI

Rizk H.F., El-Badawi M.A., Ibrahim S.A., El-Borai M.A. Synthesis of some novel heterocyclic dyes derived from pyrazole derivatives. Arab. J. Chem. 2011;4:37–44. doi: 10.1016/j.arabjc.2010.06.012. DOI

Karabacak Ç., Tilki T., Tuncer B.Ö., Cengiz M. Antimicrobial pyrazole dyes: Synthesis, characterization, and absorption characteristics. Res. Chem. Intermed. 2015;41:1985–1999. doi: 10.1007/s11164-013-1326-6. DOI

Götzinger A.C., Theßeling F.A., Hoppe C., Müller T.J.J. One-Pot Coupling-Coupling-Cyclocondensation Synthesis of Fluorescent Pyrazoles. J. Org. Chem. 2016;81:10328–10338. doi: 10.1021/acs.joc.6b01326. PubMed DOI

Milišiūnaitė V., Arbačiauskienė E., Bieliauskas A., Vilkauskaitė G., Šačkus A., Holzer W. Synthesis of pyrazolo[4′,3′:3,4]pyrido[1,2-a]benzimidazoles and related new ring systems by tandem cyclisation of vic-alkynylpyrazole-4-carbaldehydes with (het)aryl-1,2-diamines and investigation of their optical properties. Tetrahedron. 2015;71:3385–3395. doi: 10.1016/j.tet.2015.03.092. DOI

Tigreros A., Portilla J. Recent progress in chemosensors based on pyrazole derivatives. RSC Adv. 2020;10:19693–19712. doi: 10.1039/D0RA02394A. PubMed DOI PMC

Nayak N., Prasad K.S., Pillai R.R., Armaković S., Armaković S.J. Remarkable colorimetric sensing behavior of pyrazole-based chemosensor towards Cu(II) ion detection: Synthesis, characterization and theoretical investigations. RSC Adv. 2018;8:18023–18029. doi: 10.1039/C8RA02905A. PubMed DOI PMC

Mandal A.K., Suresh M., Suresh E., Mishra S.K., Mishra S., Das A. A chemosensor for heavy-transition metal ions in mixed aqueous-organic media. Sens. Actuators B Chem. 2010;145:32–38. doi: 10.1016/j.snb.2009.11.016. DOI

Swami S., Agarwala A., Behera D., Shrivastava R. Diaminomaleonitrile based chromo-fluorescent receptor molecule for selective sensing of Mn(II) and Zn(II) ions. Sens. Actuators B Chem. 2018;260:1012–1017. doi: 10.1016/j.snb.2018.01.106. DOI

Moura N.M.M., Núñez C., Santos S.M., Faustino M.A.F., Cavaleiro J.A.S., Neves M.G.P.M.S., Capelo J.L., Lodeiro C. Synthesis, Spectroscopy Studies, and Theoretical Calculations of New Fluorescent Probes Based on Pyrazole Containing Porphyrins for Zn(II), Cd(II), and Hg(II) Optical Detection. Inorg. Chem. 2014;53:6149–6158. doi: 10.1021/ic500634y. PubMed DOI

Garzón L.-M., Portilla J. Synthesis of Novel D-π-A Dyes for Colorimetric Cyanide Sensing Based on Hemicyanine-Functionalized N-(2-Pyridyl)pyrazoles. Eur. J. Org. Chem. 2019;2019:7079–7088. doi: 10.1002/ejoc.201901178. DOI

Orrego-Hernández J., Portilla J. Synthesis of Dicyanovinyl-Substituted 1-(2-Pyridyl)pyrazoles: Design of a Fluorescent Chemosensor for Selective Recognition of Cyanide. J. Org. Chem. 2017;82:13376–13385. doi: 10.1021/acs.joc.7b02460. PubMed DOI

Lee H., Berezin M.Y., Tang R., Zhegalova N., Achilefu S. Pyrazole-substituted near-infrared cyanine dyes exhibit pH-dependent fluorescence lifetime properties. Photochem. Photobiol. 2013;89:326–331. doi: 10.1111/php.12009. PubMed DOI PMC

Wang F., Duan H., Xing D., Yang G. Novel Turn-on Fluorescence Probes for Al3+ Based on Conjugated Pyrazole Schiff Base. J. Fluoresc. 2017;27:1721–1727. doi: 10.1007/s10895-017-2110-6. PubMed DOI

Naskar B., Das K., Mondal R.R., Maiti D.K., Requena A., Cerón-Carrasco J.P., Prodhan C., Chaudhuri K., Goswami S. A new fluorescence turn-on chemosensor for nanomolar detection of Al 3+ constructed from a pyridine–pyrazole system. New J. Chem. 2018;42:2933–2941. doi: 10.1039/C7NJ03955G. DOI

Islam A.S.M., Bhowmick R., Mohammad H., Katarkar A., Chaudhuri K., Ali M. A novel 8-hydroxyquinoline-pyrazole based highly sensitive and selective Al(III) sensor in a purely aqueous medium with intracellular application: Experimental and computational studies. New J. Chem. 2016;40:4710–4719. doi: 10.1039/C5NJ03153B. DOI

Ciupa A., Mahon M.F., De Bank P.A., Caggiano L. Simple pyrazoline and pyrazole “turn on” fluorescent sensors selective for Cd2+ and Zn2+ in MeCN. Org. Biomol. Chem. 2012;10:8753. doi: 10.1039/c2ob26608c. PubMed DOI

Liu J., Yee K.K., Lo K.K.W., Zhang K.Y., To W.P., Che C.M., Xu Z. Selective Ag(I) binding, H2S sensing, and white-light emission from an easy-to-make porous conjugated polymer. J. Am. Chem. Soc. 2014;136:2818–2824. doi: 10.1021/ja411067a. PubMed DOI

Dhara A., Guchhait N., Mukherjee I., Mukherjee A., Chandra Bhattacharya S. A novel pyrazole based single molecular probe for multi-analyte (Zn2+ and Mg2+) detection in human gastric adenocarcinoma cells. RSC Adv. 2016;6:105930–105939. doi: 10.1039/C6RA22869K. DOI

Paitandi R.P., Sharma V., Singh V.D., Dwivedi B.K., Mobin S.M., Pandey D.S. Pyrazole appended quinoline-BODIPY based arene ruthenium complexes: Their anticancer activity and potential applications in cellular imaging. Dalton Trans. 2018;47:17500–17514. doi: 10.1039/C8DT02947D. PubMed DOI

Paitandi R.P., Mukhopadhyay S., Singh R.S., Sharma V., Mobin S.M., Pandey D.S. Anticancer Activity of Iridium(III) Complexes Based on a Pyrazole-Appended Quinoline-Based BODIPY. Inorg. Chem. 2017;56:12232–12247. doi: 10.1021/acs.inorgchem.7b01693. PubMed DOI

Faderl S., Pal A., Bornmann W., Albitar M., Maxwell D., Van Q., Peng Z., Harris D., Liu Z., Hazan-Halevy I., et al. Kit inhibitor APcK110 induces apoptosis and inhibits proliferation of acute myeloid leukemia cells. Cancer Res. 2009;69:3910–3917. doi: 10.1158/0008-5472.CAN-08-0034. PubMed DOI PMC

Faderl S., Bueso-Ramos C., Liu Z., Pal A., Bornmann W., Ciurea D.V., Harris D., Hazan-Halevy I., Kantarjian H.M., Estrov Z. Kit inhibitor APcK110 extends survival in an AML xenograft mouse model. Investig. New Drugs. 2011;29:1094–1097. doi: 10.1007/s10637-010-9459-6. PubMed DOI PMC

Faderl S., Bornmann W., Maxwell D., Pal A., Peng Z.-H., Shavrin A., Harris D., Van Q., Zhiming L., Verstovsek S., et al. APCK110, a Novel and Potent Inhibitor of c-Kit, Blocks Phosphorylation of AKT and STAT3, Induces Apoptosis, and Inhibits Proliferation of Acute Myeloid Leukemia (AML) Cells. Blood. 2006;108:153. doi: 10.1182/blood.V108.11.153.153. DOI

Nam Y., Hwang D., Kim N., Seo H.-S., Selim K.B., Sim T. Identification of 1H-pyrazolo[3,4-b]pyridine derivatives as potent ALK-L1196M inhibitors. J. Enzym. Inhib. Med. Chem. 2019;34:1426–1438. doi: 10.1080/14756366.2019.1639694. PubMed DOI PMC

Czodrowski P., Mallinger A., Wienke D., Esdar C., Pöschke O., Busch M., Rohdich F., Eccles S.A., Ortiz-Ruiz M.J., Schneider R., et al. Structure-Based Optimization of Potent, Selective, and Orally Bioavailable CDK8 Inhibitors Discovered by High-Throughput Screening. J. Med. Chem. 2016;59:9337–9349. doi: 10.1021/acs.jmedchem.6b00597. PubMed DOI

Yoshida T., Oki H., Doi M., Fukuda S., Yuzuriha T., Tabata R., Ishimoto K., Kawahara K., Ohkubo T., Miyachi H., et al. Structural Basis for PPARα Activation by 1H-pyrazolo-[3,4-b]pyridine Derivatives. Sci. Rep. 2020;10:7623. doi: 10.1038/s41598-020-64527-x. PubMed DOI PMC

El-Gohary N.S., Gabr M.T., Shaaban M.I. Synthesis, molecular modeling and biological evaluation of new pyrazolo[3,4-b]pyridine analogs as potential antimicrobial, antiquorum-sensing and anticancer agents. Bioorg. Chem. 2019;89:102976. doi: 10.1016/j.bioorg.2019.102976. PubMed DOI

Park C.M., Jadhav V.B., Song J.-H., Lee S., Won H.Y., Choi S.U., Son Y.H. 3-Amino-1H-pyrazolopyridine Derivatives as a Maternal Embryonic Leucine Zipper Kinase Inhibitor. Bull. Korean Chem. Soc. 2017;38:595–602. doi: 10.1002/bkcs.11129. DOI

Howard S., Amin N., Benowitz A.B., Chiarparin E., Cui H., Deng X., Heightman T.D., Holmes D.J., Hopkins A., Huang J., et al. Fragment-based discovery of 6-azaindazoles as inhibitors of bacterial DNA ligase. ACS Med. Chem. Lett. 2013;4:1208–1212. doi: 10.1021/ml4003277. PubMed DOI PMC

Engers D.W., Bollinger S.R., Engers J.L., Panarese J.D., Breiner M.M., Gregro A., Blobaum A.L., Bronson J.J., Wu Y.J., Macor J.E., et al. Discovery and characterization of N-(1,3-dialkyl-1H-indazol-6-yl)-1H-pyrazolo[4,3-b]pyridin-3-amine scaffold as mGlu4 positive allosteric modulators that mitigate CYP1A2 induction liability. Bioorg. Med. Chem. Lett. 2018;28:2641–2646. doi: 10.1016/j.bmcl.2018.06.034. PubMed DOI

Engers D.W., Blobaum A.L., Gogliotti R.D., Cheung Y.Y., Salovich J.M., Garcia-Barrantes P.M., Daniels J.S., Morrison R., Jones C.K., Soars M.G., et al. Discovery, Synthesis, and Preclinical Characterization of N-(3-Chloro-4-fluorophenyl)-1H-pyrazolo[4,3-b]pyridin-3-amine (VU0418506), a Novel Positive Allosteric Modulator of the Metabotropic Glutamate Receptor 4 (mGlu4) ACS Chem. Neurosci. 2016;7:1192–1200. doi: 10.1021/acschemneuro.6b00035. PubMed DOI PMC

Giannouli V., Lougiakis N., Kostakis I.K., Pouli N., Marakos P., Skaltsounis A.-L., Horne D.A., Nam S., Gioti K., Tenta R. Design and Synthesis of New Substituted Pyrazolopyridines with Potent Antiproliferative Activity. Med. Chem. 2020;16:176–191. doi: 10.2174/1573406415666190222130225. PubMed DOI PMC

Michailidou M., Giannouli V., Kotsikoris V., Papadodima O., Kontogianni G., Kostakis I.K., Lougiakis N., Chatziioannou A., Kolisis F.N., Marakos P., et al. Novel pyrazolopyridine derivatives as potential angiogenesis inhibitors: Synthesis, biological evaluation and transcriptome-based mechanistic analysis. Eur. J. Med. Chem. 2016;121:143–157. doi: 10.1016/j.ejmech.2016.05.035. PubMed DOI

Li S.L., Zhou Y., Lu W.Q., Zhong Y., Song W.L., Liu K.D., Huang J., Zhao Z.J., Xu Y.F., Liu X.F., et al. Identification of Inhibitors against p90 ribosomal S6 kinase 2 (RSK2) through structure-based virtual screening with the inhibitor-constrained refined homology model. J. Chem. Inf. Model. 2011;51:2939–2947. doi: 10.1021/ci2002445. PubMed DOI

Smyth L.A., Matthews T.P., Collins I. Design and evaluation of 3-aminopyrazolopyridinone kinase inhibitors inspired by the natural product indirubin. Bioorg. Med. Chem. 2011;19:3569–3578. doi: 10.1016/j.bmc.2011.03.069. PubMed DOI

Vilkauskaitė G., Schaaf P., Šačkus A., Krystof V., Holzer W. Synthesis of pyridyl substituted pyrazolo[4,3-c]pyridines as potential inhibitors of protein kinases. Arkivoc. 2014;2014:135–149. doi: 10.3998/ark.5550190.p008.188. DOI

Holzer W., Vilkauskaitė G., Arbačiauskienė E., Šačkus A. Dipyrazolo[1,5-a:4’,3’-c]pyridines—A new heterocyclic system accessed via multicomponent reaction. Beilstein J. Org. Chem. 2012;8:2223–2229. doi: 10.3762/bjoc.8.251. PubMed DOI PMC

Palka B., Di Capua A., Anzini M., Vilkauskaitė G., Šačkus A., Holzer W. Synthesis of trifluoromethyl-substituted pyrazolo[4,3-c]pyridines—Sequential versus multicomponent reaction approach. Beilstein J. Org. Chem. 2014;10:1759–1764. doi: 10.3762/bjoc.10.183. PubMed DOI PMC

Vilkauskaitė G., Šačkus A., Holzer W. Sonogashira-type reactions with 5-chloro-1-phenyl-1H-pyrazole-4-carbaldehydes: A straightforward approach to pyrazolo[4,3-c]pyridines. Eur. J. Org. Chem. 2011;2011:5123–5133. doi: 10.1002/ejoc.201100626. DOI

Arbačiauskienė E., Laukaitytė V., Holzer W., Šačkus A. Metal-Free Intramolecular Alkyne-Azide Cycloaddition To Construct the Pyrazolo[4,3-f][1,2,3]triazolo[5,1-c][1,4]oxazepine Ring System. Eur. J. Org. Chem. 2015;2015:5663–5670. doi: 10.1002/ejoc.201500541. DOI

Arbačiauskienė E., Vilkauskaitė G., Šačkus A., Holzer W. Ethyl 3-and 5-triflyloxy-1H-pyrazole-4-carboxylates in the synthesis of condensed pyrazoles by Pd-catalysed cross-coupling reactions. Eur. J. Org. Chem. 2011;2011:1880–1890. doi: 10.1002/ejoc.201001560. DOI

Bieliauskas A., Krikštolaitytė S., Holzer W., Šačkus A. Ring-closing metathesis as a key step to construct 2,6-dihydropyrano[2,3-c]pyrazole ring system. Arkivoc. 2018;2018:296–307. doi: 10.24820/ark.5550190.p010.407. DOI

Milišiūnaitė V., Arbačiauskienė E., Řezníčková E., Jorda R., Malínková V., Žukauskaitė A., Holzer W., Šačkus A., Kryštof V. Synthesis and anti-mitotic activity of 2,4- or 2,6-disubstituted- and 2,4,6-trisubstituted-2H-pyrazolo[4,3-c]pyridines. Eur. J. Med. Chem. 2018;150:908–919. doi: 10.1016/j.ejmech.2018.03.037. PubMed DOI

Milišiūnaitė V., Plytninkienė E., Bakšienė R., Bieliauskas A., Krikštolaitytė S., Račkauskienė G., Arbačiauskienė E., Šačkus A. Convenient Synthesis of Pyrazolo[4′,3′:5,6]pyrano[4,3-c][1,2]oxazoles via Intramolecular Nitrile Oxide Cycloaddition. Molecules. 2021;26:5604. doi: 10.3390/molecules26185604. PubMed DOI PMC

Arbačiauskienė E., Martynaitis V., Krikštolaitytė S., Holzer W., Šačkus A. Synthesis of 3-substituted 1-phenyl-1H-pyrazole-4-carbaldehydes and the corresponding ethanones by Pd-catalysed cross-coupling reactions. Arkivoc. 2011;2011:1–21. doi: 10.3998/ark.5550190.0012.b01. DOI

Pompeu T.E.T., Alves F.R.S., Figueiredo C.D.M., Antonio C.B., Herzfeldt V., Moura B.C., Rates S.M.K., Barreiro E.J., Fraga C.A.M., Noël F. Synthesis and pharmacological evaluation of new N-phenylpiperazine derivatives designed as homologues of the antipsychotic lead compound LASSBio-579. Eur. J. Med. Chem. 2013;66:122–134. doi: 10.1016/j.ejmech.2013.05.027. PubMed DOI

Riva E., Gagliardi S., Martinelli M., Passarella D., Vigo D., Rencurosi A. Reaction of Grignard reagents with carbonyl compounds under continuous flow conditions. Tetrahedron. 2010;66:3242–3247. doi: 10.1016/j.tet.2010.02.078. DOI

Goebel M.T., Marvel C.S. The Oxidation of Grignard Reagents. J. Am. Chem. Soc. 1933;55:1693–1696. doi: 10.1021/ja01331a065. DOI

Besset C., Chambert S., Fenet B., Queneau Y. Direct azidation of unprotected carbohydrates under Mitsunobu conditions using hydrazoic acid. Tetrahedron Lett. 2009;50:7043–7047. doi: 10.1016/j.tetlet.2009.09.173. DOI

Mitsunobu O. The Use of Diethyl Azodicarboxylate and Triphenylphosphine in Synthesis and Transformation of Natural Products. Synthesis. 1981;1981:1–28. doi: 10.1055/s-1981-29317. DOI

Bräse S., Banert K. Organic Azides: Syntheses and Applications. John Wiley; New York, NY, USA: 2010.

Semina E., Žukauskaitė A., Šačkus A., De Kimpe N., Mangelinckx S. Selective Elaboration of Aminodiols towards Small Ring α- and β-Amino Acid Derivatives that Incorporate an Aziridine, Azetidine, or Epoxide Scaffold. Eur. J. Org. Chem. 2016;2016:1720–1731. doi: 10.1002/ejoc.201600036. DOI

Peterson T., Streamland T., Awad A. A Tractable and Efficient One-Pot Synthesis of 5′-Azido-5′-deoxyribonucleosides. Molecules. 2014;19:2434–2444. doi: 10.3390/molecules19022434. PubMed DOI PMC

Kuroda K., Hayashi Y., Mukaiyama T. Conversion of tertiary alcohols to tert-alkyl azides by way of quinone-mediated oxidation–reduction condensation using alkyl diphenylphosphinites. Tetrahedron. 2007;63:6358–6364. doi: 10.1016/j.tet.2007.03.176. DOI

Fischer D., Tomeba H., Pahadi N.K., Patil N.T., Huo Z., Yamamoto Y. Iodine-Mediated Electrophilic Cyclization of 2-Alkynyl-1-methylene Azide Aromatics Leading to Highly Substituted Isoquinolines and Its Application to the Synthesis of Norchelerythrine. J. Am. Chem. Soc. 2008;130:15720–15725. doi: 10.1021/ja805326f. PubMed DOI

Žukauskaitė Ž., Buinauskaitė V., Solovjova J., Malinauskaitė L., Kveselytė A., Bieliauskas A., Ragaitė G., Šačkus A. Microwave-assisted synthesis of new fluorescent indoline-based building blocks by ligand free Suzuki-Miyaura cross-coupling reaction in aqueous media. Tetrahedron. 2016;72:2955–2963. doi: 10.1016/j.tet.2016.04.010. DOI

Aoi W., Marunaka Y. Importance of pH Homeostasis in Metabolic Health and Diseases: Crucial Role of Membrane Proton Transport. Biomed Res. Int. 2014;2014:598986. doi: 10.1155/2014/598986. PubMed DOI PMC

Han J., Burgess K. Fluorescent indicators for intracellular pH. Chem. Rev. 2010;110:2709–2728. doi: 10.1021/cr900249z. PubMed DOI

Tchaikovskaya O.N., Sokolova I.V., Kuznetsova R.T., Swetlitchnyi V.A., Kopylova T.N., Mayer G.V. Fluorescence investigations of phenol phototransformation in aqueous solutions. J. Fluoresc. 2000;10:403–408. doi: 10.1023/A:1009486615346. DOI

Diamantopoulos P.T., Sofotasiou M., Papadopoulou V., Polonyfi K., Iliakis T., Viniou N.A. PARP1-driven apoptosis in chronic lymphocytic leukemia. Biomed Res. Int. 2014;2014:106713. doi: 10.1155/2014/106713. PubMed DOI PMC

Brady S.C., Allan L.A., Clarke P.R. Regulation of Caspase 9 through Phosphorylation by Protein Kinase C Zeta in Response to Hyperosmotic Stress. Mol. Cell. Biol. 2005;25:10543–10555. doi: 10.1128/MCB.25.23.10543-10555.2005. PubMed DOI PMC

Hansen T.E., Johansen T. Following autophagy step by step. BMC Biol. 2011;9:39. doi: 10.1186/1741-7007-9-39. PubMed DOI PMC

Stoimenov I., Helleday T. PCNA on the crossroad of cancer. Biochem. Soc. Trans. 2009;37:605–613. doi: 10.1042/BST0370605. PubMed DOI

Wilson G.D., McNally N.J., Dische S., Saunders M.I., Des Rochers C., Lewis A.A., Bennett M.H. Measurement of cell kinetics in human tumours in vivo using bromodeoxyuridine incorporation and flow cytometry. Br. J. Cancer. 1988;58:423–431. doi: 10.1038/bjc.1988.234. PubMed DOI PMC

Suzuki K., Kobayashi A., Kaneko S., Takehira K., Yoshihara T., Ishida H., Shiina Y., Oishi S., Tobita S. Reevaluation of absolute luminescence quantum yields of standard solutions using a spectrometer with an integrating sphere and a back-thinned CCD detector. Phys. Chem. Chem. Phys. 2009;11:9850–9860. doi: 10.1039/b912178a. PubMed DOI

Pyrazole-based lamellarin O analogues: synthesis, biological evaluation and structure-activity relationships

Convenient Synthesis of N-Heterocycle-Fused Tetrahydro-1,4-diazepinones