Synthesis of Novel Diverse Methoxybenzenes‐substituted 2 H /4 H ‐chromene Derivatives in the Presence of InBr 3 (5 mol%) and their Cytotoxic Activity

• Published in: Journal of heterocyclic chemistry Vol. 54; no. 6; pp. 3607 - 3617
• Main Authors: K., Ratnakar Reddy, D., Krishna Swaroop, N., Ravikumar, G., Sravanthi Devi, Y., Poornachandra, N., Jagadeesh Babu, C., Ganesh Kumar, Banda, Narsaiah
• Format: Journal Article
• Language: English
• Published: 01.11.2017
• ISSN: 0022-152X; 1943-5193
• DOI: 10.1002/jhet.2987

A series of novel 2‐(trifluoromethyl)‐2 H /4 H ‐chromene‐3‐carboxylate isomers 3 and 4 functionalized with diverse methoxybenzenes 2 at position 4 in compound 3 and position 2 in compound 4 were prepared in different proportions by nucleophilic substitution on ethyl 2‐hydroxy‐2‐(trifluoromethyl)‐2 H ‐chromene‐3‐carboxylate 1 in single step promoted by Indium (III) bromide (5 mol%) a Lewis acid. Regiospecific isomers 3k , 3l , 3m , and 3n prepared by using sterically bulk 1,3,5‐trimethoxy benzene substrate 2e in this reaction. Further, isomers 3a and 4a independently on reaction with amines, only compound 3a could give Michael addition products 5a–c . All the compounds 3a–n , 4a–j , and 5a–c were screened for cytotoxic activity against four human cancer cell lines and found to show high activity at micromolar concentration. The compounds 4h and 5a–c showed promising cytotoxic activity against the tested cancer cell lines. Further, these compounds 4h and 5a–c were docked with protein (1SA0) on colchicine‐binding site of β tubulin suggesting that tubulin inhibition could be the possible mechanism of action for these compounds.