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A Small Molecule with Bridged Carbonyl and Tri-fluoro-aceto-phenone Groups Impedes Microtubule Dynamics and Subsequently Triggers Cancer Cell Apoptosis |
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| Authors: | Dr. Saswat Mohapatra Varsha Gupta Dr. Prasenjit Mondal Dr. Shreyam Chatterjee Dr. Debmalya Bhunia Prof. Surajit Ghosh |
| Affiliation: | 1. Department of Organic and Medicinal Chemistry Division, CSIR-Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Jadavpur, Kolkata, West Bengal, 700032 India These authors contributed equally to this work.;2. Department of Organic and Medicinal Chemistry Division, CSIR-Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Jadavpur, Kolkata, West Bengal, 700032 India;3. The Institute of Scientific and Industrial Research, Osaka University, 8-1, Mihogaoka, Ibaraki, Osaka, 567-0047 Japan;4. Department of Bioscience & Bioengineering, Indian Institute of Technology Jodhpur, NH 62, Surpura Bypass Road, Karwar, Rajasthan, 342037 India |
| Abstract: | 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. |
| Keywords: | Microtubule targeting agent bim p53 puma apoptosis anti-cancer |