Design, synthesis, and Gaussia luciferase Assay of triorganotin(IV)-based HCV inhibitors
2015 (English)In: Medicinal Chemistry Research, ISSN 1054-2523, E-ISSN 1554-8120, Vol. 24, no 4, 1635-1643 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2015. Vol. 24, no 4, 1635-1643 p.
Organotin(IV) complexes, HCV, IC50, Viruses, Luciferase assay, RNA, SAR
IdentifiersURN: urn:nbn:se:kth:diva-163962DOI: 10.1007/s00044-014-1242-3ISI: 000350365100028ScopusID: 2-s2.0-84923860295OAI: oai:DiVA.org:kth-163962DiVA: diva2:810563
QC 201505072015-05-072015-04-132015-05-07Bibliographically approved