Small Molecule with Bridged Carbonyl and Tri-fluoro-aceto-phenone Groups Impedes Microtubule Dynamics and Subsequently Triggers Cancer Cell Apoptosis

ChemMedChem. 2021 May 13. doi: 10.1002/cmdc.202100192. Online ahead of print.ABSTRACTWe identified a new class of microtubule targeted small molecule, which showed significant anticancer activity and induces apoptotic death of cancer cells. Precisely the central bridged carbonyl group and trifluoro-acetophenone group of a bis-benzothiazole molecule (BBT) interacts with tubulin close to the curcumin site and perturbs microtubule dynamics as well as causes microtubule depolymerization. We observed a significant enhancement of fluorescence while BBT interacts with the tubulin through bridged carbonyl moiety, a similar phenomenon to colchicine. Further, BBT activates tumor-suppressing bim and p53-puma axes to inhibit cancer survival. It also shows promising results against a tumor spheroid model. BBT also capable of tumor regression, which shows that this molecule can serve as a potential template for the design of next-generation microtubule targeted anticancer drugs.PMID:33983670 | DOI:10.1002/cmdc.202100192
Source: ChemMedChem - Category: Chemistry Authors: Source Type: research