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

作者：Shah Farooq Ali^*; Fatima Kaneez; Sabir Shaista; Ali Saqib; Fischer Andreas; Qadri Mohammad Ishtiaq

来源：Medicinal Chemistry Research, 2015, 24(4): 1635-1643.

DOI：10.1007/s00044-014-1242-3

• Organotin(IV) complexes
• HCV
• IC50
• Viruses
• Luciferase assay
• RNA
• SAR

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. Structure-activity relationship studies led to the identification of Tributyltannic[3-(3',4'-dichlorophenylamido)propanoate] (compound 1) as a potent HCV inhibitor, with log IC50 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 methyl- and phenyl-substituted complexes.
HCV infection can lead to hepatocellular carcinoma, and is a major reason for liver transplantation. The worldwide prevalence of chronic HCV infection is estimated to be approaching 270-300 million people, but patients and physicians are still waiting for effective anti-HCV drugs. With this background, organotin(IV) complexes are synthesized and screened against HCV using Gaussia luciferase assay. Organotin(IV) complexes are selected due to their ability to interact with both DNA constituents and enzymes.

• 出版日期2015-4