Inhibiting the formation of amyloid fibrils is a crucial step in the prevention of the human neurological disorder, Alzheimer's disease (AD). Ionic liquid (IL) mediated interactions are an expedient approach that exhibits inhibition effects on amyloid fibrils. In view of the beneficial role of ILs, in this work we have explored complexation of anti-Alzheimer's drugs (i.e., tacrine and PC-37) and an amino acid-functionalized IL [AIL (4-PyC8)]. Maintaining standard physiological conditions, the binding mechanism, thermo-dynamical properties and binding parameters were studied by employing UV-vis, fluorescence, FTIR, 1H NMR, COSY and NOESY spectroscopy. The present investigation uncovers the fact that the interaction of anti-Alzheimer's drugs with 4-PyC8 is mediated through H-bonding and van der Waals forces. The Benesi-Hildebrand relation was used to evaluate the binding affinity and PC-37 showed the highest binding when complexed with 4-PyC8. FTIR spectra showed absorption bands at 3527.98 cm-1 and 3527.09 cm-1 for the PC-37 + 4-PyC8 system which is quite promising compared to tacrine. 1H-NMR experiments recorded deshielding for tacrine at relatively higher concentrations than PC-37. COSY investigations suggest that anti-Alzheimer's drugs after complexation with 4-PyC8 show a 1 : 1 ratio. The cross-peaks of the NOESY spectra involve correlations between anti-Alzheimer's drugs and AIL protons, indicating complexation between them. The observed results indicate that these complexes are expected to have a possible therapeutic role in reducing/inhibiting amyloid fibrils when incorporated into drug formulations.

Biomedical Research Center University Hospital Hradec Kralove Sokolska 581 500 05 Hradec Kralove Czech Republic

Department of Chemistry Faculty of Science University of Hradec Kralove Rokitanskeho 62 50003 Hradec Kralove Czech Republic

Department of Toxicology and Military Pharmacy Faculty of Military Health Sciences University of Defence Trebesska 1575 500 01 Hradec Kralove Czech Republic

MATS School of Sciences MATS University Pagaria Complex Pandri Raipur 492009 C G India

Ramrao Adik Institute of Technology DY Patil University Nerul Navi Mumbai India

School of Studies in Chemistry Pt Ravishankar Shukla University Raipur 492010 C G India

Zobrazit více v PubMed

Ouyang C. Zhang S. Xue C. Yu X. Xu H. Wang Z. Lu Y. Wu Z. S. Precision guided missile-like DNA nanostructure containing warhead and guidance control for aptamer-based targeted drug delivery into cancer cells in vitro and in vivo. J. Am. Chem. Soc. 2020;142:1265–1277. doi: 10.1021/jacs.9b09782. PubMed DOI

Wang Y. Luan Z. Zhao C. Bai C. Yang K. Target delivery selective CSF-1R inhibitor to tumor-associated macrophages via erythrocyte-cancer cell hybrid membrane camouflaged pH-responsive copolymer micelle for cancer immunotherapy. Eur. J. Pharm. Sci. 2020;142:105136. doi: 10.1016/j.ejps.2019.105136. PubMed DOI

Celebioglu A. Uyar T. Hydrocortisone/cyclodextrin complex electrospun nanofibers for a fast-dissolving oral drug delivery system. RSC Med. Chem. 2020;11:245–258. doi: 10.1039/C9MD00390H. PubMed DOI PMC

Hartmann A. K. Gudipati S. Pettenuzzo A. Ronconi L. Rouge J. L. Chimeric siRNA-DNA Surfactants for the Enhanced Delivery and Sustained Cytotoxicity of a Gold (III) Metallodrug. Bioconjugate Chem. 2020;31:1063–1069. doi: 10.1021/acs.bioconjchem.0c00047. PubMed DOI

Schittny A. Philipp-Bauer S. Detampel P. Huwyler J. Puchkov M. Mechanistic insights into effect of surfactants on oral bioavailability of amorphous solid dispersions. J. Control. Release. 2020;320:214–225. doi: 10.1016/j.jconrel.2020.01.031. PubMed DOI

Rub M. A. Naqvi A. Z. Mixed micelles of amphiphilic drug promethazine hydrochloride and surfactants (conventional and gemini) at 293.15 K to 308.15 K: Composition, interaction and stability of the aggregates. J. Colloid Interface Sci. 2011;354:700–708. doi: 10.1016/j.jcis.2010.11.005. PubMed DOI

Banjare M. K. Banjare R. K. Behera K. Pandey S. Mundeja P. Ghosh K. K. Inclusion complexation of novel synthesis amino acid based ionic liquids with β-cyclodextrin. J. Mol. Liq. 2020;299:112204. doi: 10.1016/j.molliq.2019.112204. DOI

Garcia M. T. Ribosa I. Perez L. Manresa A. Comelles F. Self-assembly, antimicrobial activity of long-chain amide-functionalized ionic liquids in aqueous solution. Colloids Surf., B. 2014;123:318–325. doi: 10.1016/j.colsurfb.2014.09.033. PubMed DOI

Pandya S. J. Kapitanov I. V. Usmani Z. Sahu R. Sinha D. Gathergood N. Ghosh K. K. Karpichev Y. An example of green surfactant systems based on inherently biodegradable IL-derived amphiphilic oximes. J. Mol. Liq. 2020:112857. doi: 10.1016/j.molliq.2020.112857. DOI

Kalhor H. R. Kamizi M. Akbari J. Heydari A. Inhibition of amyloid formation by ionic liquids: ionic liquids affecting intermediate oligomers. Biomacromolecules. 2009;10:2468–2475. doi: 10.1021/bm900428q. PubMed DOI

Debeljuh N. Barrow C. J. Henderson L. Byrne N. Structure inducing ionic liquids-enhancement of alpha helicity in the Abeta (1–40) peptide from Alzheimer's disease. Chem. Commun. 2011;47:6371–6373. doi: 10.1039/C1CC10377F. PubMed DOI

Tjernberg L. O. Näslund J. Lindqvist F. Johansson J. Karlström A. R. Thyberg J. Terenius L. Nordstedt C. Arrest of-amyloid fibril formation by a pentapeptide ligand. J. Biol. Chem. 1996;271:8545–8548. doi: 10.1074/jbc.271.15.8545. PubMed DOI

Westermark P. Engström U. Johnson K. H. Westermark G. T. Betsholtz C. Islet amyloid polypeptide: pinpointing amino acid residues linked to amyloid fibril formation. Proc. Natl. Acad. Sci. U. S. A. 1990;87:5036–5040. doi: 10.1073/pnas.87.13.5036. PubMed DOI PMC

Stanković I. M. Niu S. Hall M. B. Zarić S. D. Role of aromatic amino acids in amyloid self assembly. Int. J. Biol. Macromol. 2020;156:949–959. doi: 10.1016/j.ijbiomac.2020.03.064. PubMed DOI

Banjare M. K. Behera K. Kurrey R. Banjare R. K. Satnami M. L. Pandey S. Ghosh K. K. Self-aggregation of bio-surfactants within ionic liquid 1-ethyl-3-methylimidazolium bromide: A comparative study and potential application in antidepressants drug aggregation. Spectrochim. Acta, Part A. 2018;199:376–386. doi: 10.1016/j.saa.2018.03.079. PubMed DOI

Cruz-Vera M. Lucena R. Cárdenas S. Valcárcel M. Ionic liquid-based dynamic liquid-phase microextraction: Application to the determination of anti-inflammatory drugs in urine samples. J. Chromatogr. A. 2008;1202:1–7. doi: 10.1016/j.chroma.2008.06.035. PubMed DOI

Maresova P. Mohelska H. Dolejs J. Kuca K. Socio-economic aspects of Alzheimer's disease. Curr. Alzheimer Res. 2015;12:903–911. doi: 10.2174/156720501209151019111448. PubMed DOI

Abd-Elrahman K. S. Hamilton A. Albaker A. Ferguson S. S. mGluR5 Contribution to Neuropathology in Alzheimer Mice Is Disease Stage-Dependent. ACS Pharmacol. Transl. Sci. 2020;3:334–344. doi: 10.1021/acsptsci.0c00013. PubMed DOI PMC

Zhong S. Wang M. Zhan Y. Zhang J. Yang X. Fu S. Bi D. Gao F. Shen Y. Chen Z. Single-nucleus RNA sequencing reveals transcriptional changes of hippocampal neurons in APP23 mouse model of Alzheimer's disease. Biosci., Biotechnol., Biochem. 2020:1–8. PubMed

Cheng X. J. Gu J. X. Pang Y. P. Liu J. Xu T. Li X. R. Hua Y. Z. Newell K. A. Huang X. F. Yu Y. Liu Y. Tacrine–Hydrogen Sulfide Donor Hybrid Ameliorates Cognitive Impairment in the Aluminum Chloride Mouse Model of Alzheimer's Disease. ACS Chem. Neurosci. 2019;10:3500–3509. doi: 10.1021/acschemneuro.9b00120. PubMed DOI

Zemek F. Drtinova L. Nepovimova E. Sepsova V. Korabecny J. Klimes J. Kuca K. Outcomes of Alzheimer's disease therapy with acetylcholinesterase inhibitors and memantine. Expert Opin. Drug Saf. 2014;13:759–774. PubMed

Oset-Gasque M. J. Marco-Contelles J. L. Tacrine-natural-product hybrids for Alzheimer’s disease therapy. Curr. Med. Chem. 2020;27:4392–4400. doi: 10.2174/0929867325666180403151725. PubMed DOI

Tumiatti V. Minarini A. Bolognesi M. L. Milelli A. Rosini M. Melchiorre C. Tacrine derivatives and Alzheimer's disease. Curr. Med. Chem. 2010;17:1825–1838. doi: 10.2174/092986710791111206. PubMed DOI

Neto D. C. F. Lima J. A. Almeida J. S. F. D. D. França T. C. C. Nascimento C. J. D. Villar J. S. F. New semicarbazones as gorge-spanning ligands of acetylcholinesterase and potential new drugs against Alzheimer's disease: Synthesis, molecular modeling, NMR and biological evaluation. J. Biomol. Struct. Dyn. 2018;36:4099–4113. doi: 10.1080/07391102.2017.1407676. PubMed DOI

Korabecny J. Dolezal R. Cabelova P. Horova A. Hruba E. Ricny J. Sedlacek L. Nepovimova E. Spilovska K. Andrs M. Musilek K. 7-MEOTA–donepezil like compounds as cholinesterase inhibitors: Synthesis, pharmacological evaluation, molecular modeling and QSAR studies. Eur. J. Med. Chem. 2014;82:426–438. doi: 10.1016/j.ejmech.2014.05.066. PubMed DOI

Karasova J. Z. Mzik M. Hroch M. Korabecny J. Nepovimova E. Vorisek V. Palicka V. Kuca K. The New Acetylcholinesterase Inhibitors PC-37 and PC-48 (7-Methoxytacrine-Donepezil-Like Compounds): Characterization of Their Metabolites in Human Liver Microsomes, Pharmacokinetics and In Vivo Formation of the Major Metabolites in Rats. Basic Clin. Pharmacol. Toxicol. 2018;122:373–382. doi: 10.1111/bcpt.12922. PubMed DOI

Wang J. Cheng Y. Peng R. Cui Q. Luo Y. Li L. Co-precipitation method to prepare molecularly imprinted fluorescent polymer nanoparticles for paracetamol sensing. Colloids Surf., A. 2020;587:124342. doi: 10.1016/j.colsurfa.2019.124342. DOI

Cazón P. Vázquez M. Velazquez G. Composite films with UV-barrier properties based on bacterial cellulose combined with chitosan and poly(vinyl alcohol): Study of puncture and water interaction properties. Biomacromolecules. 2019;20:2084–2095. doi: 10.1021/acs.biomac.9b00317. PubMed DOI

Sharma S. Banjare M. K. Singh N. Korábečný J. Fišar Z. Kuča K. Ghosh K. K. Exploring spectroscopic insights into molecular recognition of potential anti-Alzheimer's drugs within the hydrophobic pockets of β-cycloamylose. J. Mol. Liq. 2020:113269. doi: 10.1016/j.molliq.2020.113269. DOI

Banjare M. K. Behera K. Satnami M. L. Pandey S. Ghosh K. K. Host–guest complexation of ionic liquid with α-and β-cyclodextrins: a comparative study by 1H-NMR, 13C-NMR and COESY. New J. Chem. 2018;42:14542–14550. doi: 10.1039/C8NJ01840E. DOI

Jeon Y. J. Kim S. Y. Ko Y. H. Sakamoto S. Yamaguchi K. Kim K. Novel molecular drug carrier: encapsulation of oxaliplatin in cucurbit [7] uril and its effects on stability and reactivity of the drug. Org. Biomol. Chem. 2005;3:2122–2125. doi: 10.1039/B504487A. PubMed DOI

Li B. Meng Z. Li Q. Huang X. Kang Z. Dong H. Chen J. Sun J. Dong Y. Li J. Jia X. A pH responsive complexation-based drug delivery system for oxaliplatin. Chem. Sci. 2017;8:4458–4464. doi: 10.1039/C7SC01438D. PubMed DOI PMC

Di Pasqua A. J. Kerwood D. J. Shi Y. Goodisman J. Dabrowiak J. C. Stability of carboplatin and oxaliplatin in their infusion solutions is due to self-association. Dalton Trans. 2011;40:4821–4825. doi: 10.1039/C0DT01758B. PubMed DOI

Bakirci H. Nau W. M. Fluorescence regeneration as a signaling principle for choline and carnitine binding: a refined supramolecular sensor system based on a fluorescent azoalkane. Adv. Funct. Mater. 2006;16:237–242. doi: 10.1002/adfm.200500219. DOI

Ahmadi S. Dabbagh H. A. Grieco P. Balalaie S. A cystine-based dual chemosensor for fluorescent-colorimetric detection of CN− and fluorescent detection of Fe3+ in aqueous media: Synthesis, spectroscopic, and DFT studies. Spectrochim. Acta, Part A. 2020;228:117696. doi: 10.1016/j.saa.2019.117696. PubMed DOI

Thordarson P. Determining association constants from titration experiments in supramolecular chemistry. Chem. Soc. Rev. 2011;40:1305–1323. doi: 10.1039/C0CS00062K. PubMed DOI

Singh N. Pagariya D. Jain S. Naik S. Kishore N. Interaction of copper (II) complexes by bovine serum albumin: Spectroscopic and calorimetric insights. J. Biomol. Struct. Dyn. 2018;36:2449–2462. doi: 10.1080/07391102.2017.1355848. PubMed DOI

Sharma S. Singh N. Nepovimova E. Korabecny J. Kuca K. Satnami M. L. Ghosh K. K. Interaction of synthesized nitrogen enriched graphene quantum dots with novel anti-Alzheimer’s drugs: spectroscopic insights. J. Biomol. Struct. Dyn. 2020;38:1822–1837. PubMed

Canteri M. H. Renard C. M. Le Bourvellec C. Bureau S. ATR-FTIR spectroscopy to determine cell wall composition: application on a large diversity of fruits and vegetables. Carbohydr. Polym. 2019;212:186–196. doi: 10.1016/j.carbpol.2019.02.021. PubMed DOI

Rosi F., Cartechini L., Monico L., Gabrieli F., Vagnini M., Buti D., Doherty B., Anselmi C., Brunetti B. G. and Miliani C., Tracking metal oxalates and carboxylates on painting surfaces by non-invasive reflection mid-FTIR spectroscopy, in Metal Soaps in Art, Springer, Cham, 2019, pp. 173–193

Mohsin G. F. Schmitt F. J. Kanzler C. Hoehl A. Hornemann A. PCA-based identification and differentiation of FTIR data from model melanoidins with specific molecular compositions. Food Chem. 2019;281:106–113. doi: 10.1016/j.foodchem.2018.12.054. PubMed DOI

Hou H. Lin X. Zhu W. Dang W. Niu D. Yang J. Liu S. Jiao B. Li Q. Physicochemical properties, 1H NMR, ab initio calculations and molecular interactions in a binary mixture of N-methylimidazole with ethyl acetate. J. Mol. Liq. 2019;275:586–598. doi: 10.1016/j.molliq.2018.11.052. DOI

Mari S. H. Varras P. C. Choudhary I. M. Siskos M. G. Gerothanassis I. P. Solvent-Dependent Structures of Natural Products Based on the Combined Use of DFT Calculations and 1H-NMR Chemical Shifts. Molecules. 2019;24:2290. doi: 10.3390/molecules24122290. PubMed DOI PMC

Prominent Perspective on Existing Biological Hallmarks of Alzheimer's Disease