Synthesis and Biological Evaluation of Pyrazoline and Pyrrolidine‐2,5‐dione Hybrids as Potential Antitumor Agents

• DOI: 10.1002/cmdc.202000458
• Publication Date: 2020-07-27T05:53:50Z
• Authors: Kalpana Tilekar; Neha Upadhyay; Franz‐Josef Meyer...; Fulvio Loiodice; Natalia Y. Anisimova; Tatiana S. Spirina; Darina V. Sokolova; Galina B. Smirnova; Jun‐yong Choe; Vadim S. Pokrovsky; Antonio Lavecchia; C S Ramaa
• Keywords: Pyrrolidine; Pyrazoline

In search of novel and effective antitumor agents, pyrazoline-substituted pyrrolidine-2,5-dione hybrids were designed, synthesized evaluated in silico, vitro vivo for anticancer efficacy. All the compounds exhibited remarkable cytotoxic effects MCF7 HT29 cells. The excellent antiproliferative activity toward (IC50 =0.78±0.01 μM), =0.92±0.15 μM) K562 =47.25±1.24 cell lines, prompted us to further investigate best compound S2 (1-(2-(3-(4-fluorophenyl)-5-(p-tolyl)-4,5-dihydro-1H-pyrazol-1-yl)-2-oxoethyl)pyrrolidine-2,5-dione). cell-cycle analysis, was found disrupt growth phases with increased population G1 /G0 phase decreased G2 /M phase. also supported by inhibition anti-apoptotic protein Bcl-2. tumor regression studies xenograft nude mice, equivalent promising maximum TGI, 66 % (i. p. route) 60 (oral at 50 mg kg-1 dose both routes, indicating oral bioavailability These findings advocate that hybridization pyrazoline pyrrolidine-2,5-dioes holds promise development more potent less toxic agents.