Design, synthesis, and Gaussia luciferase Assay of triorganotin(IV)-based HCV inhibitors

Abstract

The discovery and optimization of a novel triorganotin(IV) complexes with anti-HCV properties are presented. Organotin(IV) moiety has the ability to bind phosphate group of RNA backbone. The organotin(IV) moiety is bonded with ligands and groups, which are known for inhibiting HCV enzymes. Triorganotin(IV) complexes were synthesized and evaluated for their potency against HCV by using luciferase assay. Structureactivity relationship studies led to the identification of Tributyltannic[3-(3 0 ,4 0 -dichlorophenylamido)propanoate] (compound 1) as a potent HCV inhibitor, with log IC 50 values 0.79 nM in the cell-based assay. Triorganotin(IV) complexes containing chlorine and nitro group display higher potency. Gaussia luciferase Assay shows that among triorganotin(IV) derivatives, butyl substituted triorganotin(IV) complexes are more active than methyland phenyl-substituted complexes.

Organotin(iv) based anti-HCV drugs: synthesis, characterization and biochemical activity

“…Previously, we have been working on determining the importance of ligands and substitution on these ligands in anti-HCV activity of the compounds. 41 Optimization of ligand suggests the use of the ligand with the least numbers of polar groups for improvement of activity. In the present case, a symmetrical and small sized ligand with carboxylate as the only polar group was selected.…”