Design, structure-activity relationship study and biological evaluation of the thieno[3, 2-c]isoquinoline scaffold as a potential anti-cancer agent. (15th November 2021)

• Record Type: Journal Article
• Authors: Liu, Jiang Tian; Jaunky, Dilan B.; Larocque, Kevin; Chen, Fei; Mckibbon, Keegan; Sirouspour, Mehdi; Taylor, Sarah; Shafeii, Alexandre; Campbell, Donald; Braga, Helena; Piekny, Alisa; Forgione, Pat
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 52(2021)
• Publication Date: 2021-11-15
• Subjects: SAR Structure-Activity Relationship -- MTA microtubules targeting agent -- IC50 half maximal inhibitory concentration -- cLogP predicate partition coefficient -- NIS N-Iodoscuccinimide -- NCS N-chlorosuccinimide -- GTP guanosine triphosphate. DMSO, dimethyl sulfoxide; Anticancer -- SAR study -- Microtubules -- Thienoisoquinoline -- Colchicine; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2021.128327
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphic abstract: Abstract: Several derivatives of a series that share a thienoisoquinoline scaffold have demonstrated potent activity against cancer cell lines A549, HeLa, HCT-116, and MDA-MB-231 in the submicromolar concentration range. Structure-activity relationship (SAR) studies on a range of derivatives aided in identifying key pharmacophores in the lead compound. A series of compounds have been identified as the most promising with submicromolar IC50 values against a lung cancer cell line (A549). Microscopy studies of cancer cells treated with the lead compound revealed that it causes mitotic arrest and disrupts microtubules. Further evaluation via an in vitro microtubule polymerization assay and competition studies indicate that the lead compound binds to tubulin via the colchicine site.