Hepatitis C virus (HCV) is a major cause of end-stage liver diseases like cirrhosis and hepatocarcinoma, posing a serious worldwide threat when left untreated. Nowadays, direct-acting antivirals (DAAs) constitute core components of anti-HCV treatment. Nonetheless, some DAAs are associated with a growing level of drug resistance as well as adverse reactions. That is why introducing new anti-HCV drugs with higher potency and lower toxicity is so essential. NS5B polymerase is an HCV non-structural protein that acts as a critical target for the development of anti-HCV therapeutics. Based on the necessary pharmacophores for inhibition of HCV NS5B polymerase, a novel series of phthalamide analogs that harbor the potential of NS5B polymerase inhibition to stop HCV proliferation in a cell-based assay were designed, synthesized, and in-vitro evaluated. Interestingly, all compounds displayed low cellular cytotoxicity in Huh 7.5 cells (CC 50 > 100). Compound 28 with EC 50 of 6.0 µM, and an appropriate a nity to NS5B polymerase active site could be considered as a new hit compound, providing useful information for the design of novel HCV inhibitors.
Hepatitis C virus (HCV) is a major cause of end-stage liver diseases like cirrhosis and hepatocarcinoma, posing a serious worldwide threat when left untreated. Nowadays, direct-acting antivirals (DAAs) constitute core components of anti-HCV treatment. Nonetheless, some DAAs are associated with a growing level of drug resistance as well as adverse reactions. That is why introducing new anti-HCV drugs with higher potency and lower toxicity is so essential. NS5B polymerase is an HCV non-structural protein that acts as a critical target for the development of anti-HCV therapeutics. Based on the necessary pharmacophores for inhibition of HCV NS5B polymerase, a novel series of phthalamide analogs that harbor the potential of NS5B polymerase inhibition to stop HCV proliferation in a cell-based assay were designed, synthesized, and in-vitro evaluated. Interestingly, all compounds displayed low cellular cytotoxicity in Huh 7.5 cells (CC 50 > 100). Compound 28 with EC 50 of 6.0 µM, and an appropriate affinity to NS5B polymerase active site could be considered as a new hit compound, providing useful information for the design of novel HCV inhibitors.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.