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Synthesis, Docking Study, and Biological Evaluation of 2-Phenylchroman-4-One Derivatives As Murine Double Minute 2 (Mdm2) Inhibitors Publisher



Talebi M1 ; Boumi S1 ; Nezamtaheri MS2 ; Sarmad Y1 ; Hosseini FS1 ; Delphi L3 ; Goliaei B2 ; Amini M1 ; Amanlou M1, 4
Authors

Source: ChemistrySelect Published:2023


Abstract

Inhibiting the interaction between the p53 tumor suppressor and its negative regulator murine double minute 2 (MDM2) is a promising therapeutic opportunity in cancer drug research. Herein, we describe the design, synthesis, and in vitro screening of phenyl chroman-based derivatives 7 a–l as MDM2 inhibitors. Among target compounds, 7 e, 7 h, and 7 j had considerable cytotoxicity activity at concentrations of 50 μM and 100 μM against MCF7 and HCT-116 cell lines. Designed compounds that demonstrated good toxicity, were selected for enzyme inhibition assay. The most potent MDM2 inhibitor in this series is compound 7 h, which showed a Ki value of 13.66 μM. Moreover, compound 7 h with acceptable safety profiles in normal cells was found the least effective compound against human umbilical vein endothelial cells (HUVECs). In addition, cell cycle analysis was also investigated for representative compound 7 h. Also, the docking study was done to predict the possible interaction between the synthesized compound and both MDM2 and murine double minute x (MDMX) proteins. Interestingly, the docking results were in good agreement with the experimental assay. © 2023 Wiley-VCH GmbH.
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