Si, Dongjuan published the artcileDesign, synthesis and biological evaluation of novel pyrrolidone-based derivatives as potent p53-MDM2 inhibitors, COA of Formula: C9H10O3, the main research area is pyrrolidone derivative design synthesis antitumor activity; p53 MDM2 inhibitor pyrrolidone derivative structure activity relationship; Chalcone; Virtual screening; p53-MDM2; p53-MDM2 inhibitors; pyrrolidone.
Inhibition of the interactions of the tumor suppressor protein p53 with its neg. regulators MDM2 in vitro and in vivo, representing a valuable therapeutic strategy for cancer treatment. The natural product chalcone exhibited moderate inhibitory activity against MDM2, thus based on the binding mode between chalcone and MDM2, a hit unsaturated pyrrolidone scaffold was obtained through virtual screening. Several unsaturated pyrrolidone derivatives were synthesized and biol. evaluated. As a result, because the three critical hydrophobic pockets of MDM2 were occupied by the substituted-Ph linked at the pyrrolidone fragment, compound I demonstrated good binding affinity with the MDM2. Addnl., compound I also showed excellent antitumor activity and selectivity, and no cytotoxicity against normal cells in vitro. The further antitumor mechanism studies were indicated that compound I could successfully induce the activation of p53 and corresponding downstream p21 proteins, thus successfully causing HCT116 cell cycle arrest in the G1/M phase and apoptosis. Thus, the novel unsaturated pyrrolidone p53-MDM2 inhibitors could be developed as novel antitumor agents.
Bioorganic Chemistry published new progress about Antitumor agents. 104-01-8 belongs to class isoquinoline, name is 4-Methoxyphenylacetic acid, and the molecular formula is C9H10O3, COA of Formula: C9H10O3.
Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem