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Updated: Oct 23, 2025

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
Design, structure-activity relationship study and biological evaluation of the thieno[3,2-c]isoquinoline scaffold as
Jiang Tian Liu1, Dilan B Jaunky2, Kevin Larocque2
1Department of Chemistry & Biochemistry, Concordia University, 7141 rue Sherbrooke O., Montréal, QC H4B 1R6, Canada.
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.
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