Design, Synthesis, and In Silico Analyses of Nitroimidazole Derivatives Targeting Cholinesterases

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dc.contributor.authorBiyik, Busra
dc.contributor.authorTarikogullari, Ayse H.
dc.contributor.authorAlagoz, Mehmet Abdullah
dc.contributor.authorDemir, Yeliz
dc.contributor.authorGulcin, Ilhami
dc.contributor.authorBurmaoglu, Serdar
dc.contributor.authorAlgul, Oztekin
dc.date.accessioned2026-04-04T13:37:36Z
dc.date.available2026-04-04T13:37:36Z
dc.date.issued2025
dc.departmentİnönü Üniversitesi
dc.description.abstractThe increasing incidence of diseases and the constraints of current treatments require expedited drug development. Drug repositioning presents an effective approach for discovering new therapeutic applications for drugs already in clinical use. This study examines the efficacy of metronidazole and secnidazole, which are presently utilized as antiprotozoal agents, in the treatment of Alzheimer's disease via ester modifications. The secondary alcohol group in nitroimidazole structures underwent esterification with acetyl, pivaloyl, cyclopropyl, and cyclohexyl carbonyl chlorides. The compounds exhibited significant inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), with Ki values between 52.40 +/- 6.99 nM and 240.80 +/- 45.56 nM for AChE and 77.82 +/- 18.01 nM and 323.70 +/- 56.21 nM for BChE. Molecular docking studies demonstrated significant interactions of the most active compounds (MNZ 8 and MNZ 4) with essential residues, including Trp84 and Phe330 in AChE, as well as Trp82 and active-site water molecules in BChE. These findings corroborate their inhibitory potential, notwithstanding initial positional alterations observed during simulations. The synthesized compounds' absorption, distribution, metabolism, elimination, and toxicity (ADMET) properties were also assessed in silico. All compounds demonstrated drug-like properties and did not exhibit undesirable toxic effects. The findings indicate that repositioned derivatives of metronidazole and secnidazole may serve as promising lead compounds for the development of cholinesterase inhibitors aimed at treating Alzheimer's disease.
dc.description.sponsorshipMersin University [BAP-SBE-2021-2-TP2-4423]
dc.description.sponsorshipThe authors thank Mersin University for their financial support (BAP-SBE-2021-2-TP2-4423). The authors would also like to thank the Mersin University Advanced Technology Education, Research, and Application Center (MEITAM) for their valuable assistance.
dc.identifier.doi10.1002/slct.202502275
dc.identifier.issn2365-6549
dc.identifier.issue35
dc.identifier.scopus2-s2.0-105015525970
dc.identifier.scopusqualityN/A
dc.identifier.urihttps://doi.org/10.1002/slct.202502275
dc.identifier.urihttps://hdl.handle.net/11616/109936
dc.identifier.volume10
dc.identifier.wosWOS:001570640000001
dc.identifier.wosqualityQ3
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.language.isoen
dc.publisherWiley-V C H Verlag Gmbh
dc.relation.ispartofChemistryselect
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_WOS_20250329
dc.subjectAChE
dc.subjectAlzheimer's disease
dc.subjectBChE
dc.subjectDrug repositioning
dc.subjectMetronidazole
dc.subjectSecnidazole
dc.titleDesign, Synthesis, and In Silico Analyses of Nitroimidazole Derivatives Targeting Cholinesterases
dc.typeArticle

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