Isolation and characterization of novel hydroxyflavone from Kigelia africana (Lam.) Benth. fruit ethyl acetate fraction against CHO 1 and HeLa cancer cell lines: In vitro and in silico studies

Abstract

This study is aimed at evaluating the anti-proliferative activity of a novel hydroxyflavone isolated for the first time from Kigelia africana fruit, against cervical cancer (HeLa) and tumorigenic (CHO-1) cells, and understanding the molecular interaction of the compound against p53 protein target. Compound 1 was isolated and characterization was done via application of physical and spectroscopic approaches (1D-NMR, 2D-NMR, and mass spectroscopy) and its effect on CHO-1 and HeLa cell lines was evaluated. Also, the compound was docked to different conformers obtained from the cluster analysis of the molecular dynamics simulation trajectories of the wild and mutant human p53 core domain protein. The resultant complexes were subjected to a 100 ns molecular dynamics simulation (MDs). A novel hydroxyflavone isolated from Kigelia africana fruit ethyl acetate fraction was identified and characterized as 3,6-dihydroxy-2-(3,4-dimethylphenyl)-4H-chromen-4-one. This compound displayed an anti-proliferative effect on CHO 1 cells with IC50 value of 74.0±10.4 µg/mL but had no significant effect on HeLa cell lines. Compound 1 was able to selectively bind more strangely to the mutant p53 core domain than the wild type in a similar binding manner as the reference compound. The MDs analysis reveals that the binding of Compound 1 to the mutant p53 structure stabilized the protein, which is one of the key mechanisms that was proposed for the restoration of wild-type p53 conformation in p53-Y220C cells. The isolated compound might serve as a starting point for the development of novel anti-proliferative treatments for polycystic ovarian syndrome (PCOS) in reproductive women.