Synthesis and antitumor activity of novel phenylhydrazonopyrazolone derivatives and molecular dynamics simulations

SHP2 is a new promising target for anti-cancer drug discovery. A series of novel phenylhydrazonopyrazolone derivatives was synthesized by a more convenient method, and their chemical structures were characterized by various spectroscopic methods. The inhibitory effects of these compounds on SHP2 enzyme and SHP2-dependent cancer cell H1975 were evaluated. The compound 11f with IC 50 value of 3.38 μmol/L exhibited more potent antitumor activity against H1975 cell than GS-493 (IC 50 = 20.92 μmol/L). Molecular dynamics simulation of compound 11f displayed a possible mode of interaction between this compound and SHP2 enzyme.