Evaluation of -substituted acridone-based derivatives as AKT inhibitors against breast cancer cells: in vitro and molecular docking studies.

Unlabelled: A series of -substituted acridone-2-carboxamide derivatives were synthesized and evaluated for their potent anti-cancer agents targeting AKT kinase. In vitro cytotoxicity activity of the target compounds was tested against breast cancer cell lines (MCF-7 and MDA-MB-231). Among the tested compounds, four compounds (, , , and ) exhibited promising anti-cancer activity against both cancer cell lines. Notably, compound demonstrated the highest activity against MCF-7 and MDA-MB-231 at IC values of 4.72 and 5.53 μM, respectively. In vitro AKT kinase activity revealed that compounds and were the most potent AKT inhibitors with IC values of 5.38 and 6.90 μM, respectively. In addition, the quantitative ELISA method of testing confirmed that compound effectively inhibited cell proliferation by suppressing the activation of p-AKT Ser. Furthermore, molecular docking studies revealed that compound can bind well to the active site of the AKT enzyme. The in silico ADME studies suggested that all synthesized molecules showed good oral bioavailability with a low-toxicity profile and can be used for further optimization as AKT kinase inhibitors in the treatment of breast cancer.

Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03524-z.