Design, synthesis and anticancer evaluation of some novel 7-hydroxy-4-methyl-3-substituted benzopyran-2-one derivatives.

ABSTRACT

Aim: 22 derivatives of 7-hydroxy-4-methyl-3-substituted benzopyran-2-one were designed, synthesized and evaluated for their anticancer activity. Materials & methods: The prepared compounds were screened for their cytotoxicity against the MCF-7 breast cancer cell line. The best five were then evaluated against MCF10a to check their safety and then tested for their PI3K and Akt-1 inhibitory action. The best two derivatives were further analyzed through cell cycle analysis, caspase 3/7 activation, increasing BAX level and decreasing BCL-2. Docking and absorption, distribution, metabolism and excretion prediction studies were also performed. Results & conclusion: Compounds 3b, 3c, 3j, 7 and 8 were the most active. Compounds 3c and 8 showed remarkable inhibitory action against PI3K and Akt-1 enzymes, and both are promising candidates for treatment of breast cancer.