Evaluating the therapeutic potential of 4-hydroxyflavanes diastereomers derivatives against (MetAP2) for anti-cancer therapy: a molecular docking study

Abstract The 4-hydroxyflavanes are derived from flavanones through a condensation reaction with a primary amine; therefore, the 4-hydroxyflavanes derivatives have been shown to have key biological actions such as aldose reductase inhibition, cancer chemoprevention, antibacterial and anti-inflammatory effects. In this study, we investigated the molecular docking interactions between 2-phenyl-4 (phenylamino)chroman-4-ol, 4-((3-chlorophenyl) amino)-2-phenylchroman-4-ol and 4-((3-methoxyphenyl) amino)-2-phenylchroman-4-ol diastereomers with methionine aminopeptidase II (MetAP2) which is an enzyme that is essential for tissue healing and cancer progression in humans, in order to find novel antiangiogenic agents. The molecular docking program used in this work was Moe software. The binding affinity composed of (MetAP2) with 4-((3-methoxyphenyl) amino)-2-phenylchroman-4-ol diastereomers derivatives (RR, RS, SR, SS) were found to be the most stable, with the free energy of −7.06, −7.85, −7.44, and −7.82 kcal/mol docking score and the RMSD 1.77, 1.24, 1.93 and 1.41 respectively; specifically, the RS configuration. The findings provide insights into the potential efficacy of 4-hydroxyflavanes derivatives as a (MetAP2) inhibitor, which could have implications for the development of novel cancer therapeutics.