Anticancer SAR establishment and α/β-tubulin isoform specific targeting: a detailed insight of the anticancer potential of 4-chromene derivatives

• Published in: New journal of chemistry 2023-05, Vol.47 (18), p.8589-861
• Main Authors: Mayank, Singh, Ashutosh, Saumya, Kumar Udit, Joshi, Mayank, Kaur, Navneet, Garg, Neha, Singh, Narinder
• Format: Article
• ISSN: 1144-0546; 1369-9261
• DOI: 10.1039/d2nj04822a

4 H -Chromene derivatives are promising anticancer compounds known to bind within the colchicine binding site of the tubulin protein. Among these, the 2-amino-4-phenyl-4 H -benzo[ h ]chromene-3-carbonitrile-based 4 H -chromenes scaffold is known to produce a significant impact on tubulin proteins. Other molecules with similar pharmacophores are also known for their colchicine binding site targeting abilities. However, tubulin is not a single protein; multiple isoforms have been reported, and some are comparatively more important under malignant conditions. Therefore, the research findings presented herein include a detailed understanding of the interaction pattern of the 2-amino-4-phenyl-4 H -benzo[ h ]chromene-3-carbonitrile series for their colchicine binding ability against various tubulin isoforms proteins. We have established the current series anticancer potential and structural activity relationship. The series revealed promising anticancer potential, and MNC-1 was the best among all. However, a serious side effect of this scaffold is a major problem, as these derivatives indiscriminately bind to the tubulin of malignant and normal cells. However, the expression profile of tubulin isoforms was found to be different in normal and malignant cell types. Therefore, selective killing of the malignant cell seems possible by designing a 4 H -chromenes derivative selective against particular tubulin isoforms. The insights provided herein clearly indicate the differences in the binding pattern of different 4 H -chromenes derivatives against different tubulin isoforms. Therefore, with precise structural modification, these molecules' selective targeting against cancer cells seems quite possible. The anticancer activity of chromene derivatives was explored. MNC-1 showed the best anticancer potential and is expected to deliver the best activity against cancer cells with β1 and/or β8 over-expression.