Design and synthesis of new HCV NS3/4A protease inhibitors to effective against drug resistance

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dc.contributor.authorOksuz, Zehra
dc.contributor.authorAktekin, Mine Buga
dc.contributor.authorAlagoz, Mehmet Abdullah
dc.contributor.authorKuzucu, Mehmet
dc.contributor.authorSerin, Mehmet Sami
dc.contributor.authorAlgul, Oztekin
dc.date.accessioned2026-04-04T13:34:54Z
dc.date.available2026-04-04T13:34:54Z
dc.date.issued2025
dc.departmentİnönü Üniversitesi
dc.description.abstractHCV NS3/4A protease is a crucial target for antiviral therapy, but resistance remains a significant challenge. Understanding substrate recognition is key to developing effective inhibitors. The aim of this study was to investigate four new compounds (10-12 and 13) that mimic natural substrate binding. Compound activities were determined with enzymatic assays and anti-proliferative activities were evaluated. Compound 12 exhibited the highest potency with an IC50 of 17.78 mu M and a Ki value of 16.39 mu M. All compounds demonstrated moderate to high anti-proliferative activity against HFF-1 and HepG2 cells, with 12 and 11 showing the most potent effects. In silico studies revealed that compounds 11 and 12 formed stable complexes with the HCV NS3/4A protease, establishing significant interactions with key residues of the catalytic triad. Their docking scores and molecular dynamics simulations were comparable to those of the reference molecule, simeprevir. These findings suggest that compounds 10-12 and 13 hold promise as potential therapeutic agents against HCV, warranting further investigation.
dc.description.sponsorshipMersin University [2020-1-APA-4082 (AP4-C) BAP]
dc.description.sponsorshipThis study was supported by 2020-1-APA-4082 (AP4-C) BAP Projects of Mersin University. The authors would also like to thank Mersin University Advanced Technology Education, Research and Application Center (MEITAM) for their valuable assistance.
dc.identifier.doi10.1016/j.molstruc.2025.142087
dc.identifier.issn0022-2860
dc.identifier.issn1872-8014
dc.identifier.orcid0000-0002-7786-7687
dc.identifier.scopus2-s2.0-105000676984
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.1016/j.molstruc.2025.142087
dc.identifier.urihttps://hdl.handle.net/11616/109484
dc.identifier.volume1336
dc.identifier.wosWOS:001455768300001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.language.isoen
dc.publisherElsevier
dc.relation.ispartofJournal of Molecular Structure
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_WOS_20250329
dc.subjectProtease inhibitors
dc.subjectHCV NS3/4A
dc.subjectBis structure
dc.subjectBenzimidazole
dc.subjectIn silico
dc.titleDesign and synthesis of new HCV NS3/4A protease inhibitors to effective against drug resistance
dc.typeArticle

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