A Small Molecule with Bridged Carbonyl and Tri-fluoro-aceto-phenone Groups Impedes Microtubule Dynamics and Subsequently Triggers Cancer Cell Apoptosis.
We identified a new microtubule targeted small molecule, which showed significant anticancer activity and induced 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 is 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.
['Mohapatra|Saswat|S|', 'Gupta|Varsha|V|', 'Mondal|Prasenjit|P|', 'Chatterjee|Shreyam|S|', 'Bhunia|Debmalya|D|', 'Ghosh|Surajit|S|http://orcid.org/0000-0002-8203-8613']
apoptosis bim Microtubule targeting agent anti-cancer p53 puma