Tethered Aryl Groups Increase the Activity of Anti-Proliferative Thieno[2,3-b]Pyridines by Targeting a Lipophilic Region in the Active Site of PI-PLC.

ABSTRACT: The compounds 2-amino-3-carboxamido-thieno[2,3-b]pyridines have demonstrated excellent anti-proliferative activity against human cancer cell lines, including the triple-negative breast cancer cell line MDA-MB-231. In this study, 81 novel thieno[2,3-b]pyridines were synthesised in four series to further improve their anti-proliferative activity, in particular by targeting an adjacent lipophilic pocket in the putative target enzyme phosphoinositide phospholipase C (PI-PLC). Overall, it was found that appending a propyl-aryl group at C-5 on 2-amino-3-carboxamido-thieno[2,3-b]pyridine resulted in compounds with potent biological activity, exhibiting IC₅₀ values in the nanomolar range. The propyl linker could be an α,β-unsaturated ketone or a saturated propyl ket

SUBMITTER: Haverkate NA 

PROVIDER: S-EPMC8705770 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature