Antimicrobial and cytotoxic activity of 2-amino-4H-chromenes

Résumé fourni par la source

Although some 2-amino-4H-chromenes displayed moderate activity against S. mitis (1, 2, 4, 5, 6, 7, 9, and 10), S. salivarius (3 and 9), and L. paracasei (1 and 6), most of the compounds displayed weak activity against most of the bacteria involved in dental caries and were inactive against C. albicans and C. krusei. On the other hand, compounds 4 (IC50 < 2.47 µM, SI > 2564) and 8 (IC50 = 37.74 µM, SI > 154.80) displayed the highest anticancer activity against the MCF-7 and HeLa cell lines. Although compounds 4 and 5 displayed only moderate activity against U-251MG cells, their high SI values (>82.78 and >81.60, respectively) make them promising candidates for further investigation as antiproliferative agents. Molecular docking simulations help us to rationalize potential molecular targets for compounds 1-10 reported herein. All molecules were docked into four receptors/enzymes (β-tubulin, CDK4/6, ERα, and EGFR), and in two of them (EGFR and CDK4/6), compounds 8R and 5R ranked favorably within their respective docking protocols and displayed relevant interactions with N842 and L83 residues in their respective active sites. These findings are consistent with in vitro cytotoxic assays and highlight the potential of compounds 1-10 to guide the design of more potent and selective anticancer candidates.