Design and synthesis of new HCV NS3/4A protease inhibitors to effective against drug resistance
Küçük Resim Yok
Tarih
2025
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Elsevier
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
HCV 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.
Açıklama
Anahtar Kelimeler
Protease inhibitors, HCV NS3/4A, Bis structure, Benzimidazole, In silico
Kaynak
Journal of Molecular Structure
WoS Q Değeri
Q2
Scopus Q Değeri
Q1
Cilt
1336
