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- Title
Evaluation of N<sup>10</sup>-substituted acridone-based derivatives as AKT inhibitors against breast cancer cells: in vitro and molecular docking studies.
- Authors
Yadav, Tanuja T.; Patil, Piyush D.; Shaikh, Gulam Moin; Kumar, Maushmi S.; Chintamaneni, Meena; YC, Mayur
- Abstract
A series of N10-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 (7f, 8d, 8e, and 8f) exhibited promising anti-cancer activity against both cancer cell lines. Notably, compound 8f demonstrated the highest activity against MCF-7 and MDA-MB-231 at IC50 values of 4.72 and 5.53 μM, respectively. In vitro AKT kinase activity revealed that compounds 7f and 8f were the most potent AKT inhibitors with IC50 values of 5.38 and 6.90 μM, respectively. In addition, the quantitative ELISA method of testing confirmed that compound 8f effectively inhibited cell proliferation by suppressing the activation of p-AKT Ser473. Furthermore, molecular docking studies revealed that compound 8f 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.
- Subjects
MOLECULAR docking; CANCER cells; BINDING sites; BREAST cancer; CELL lines; BREAST
- Publication
3 Biotech, 2023, Vol 13, Issue 4, p1
- ISSN
2190-572X
- Publication type
Article
- DOI
10.1007/s13205-023-03524-z