title: Design, Synthesis, and Biological Evaluation of Pyrazole Derivatives.
abstract: In this in vitro study, a series of novel pyrazole derivatives were designed, synthesized, and evaluated against five human cancer cell lines (PC3, A549, HL60, HCT116, and SW620) for their antiproliferative and p53-MDM2 binding inhibitory activities. Although biological evaluations showed that this series of compounds possessed weak p53-MDM2 inhibitory activities, most of them displayed moderate to potent antiproliferative activities against the tested cells lines. Compound 11c exhibited the best potency for MDM2 (FP-IC50 = 29.22 μm) and demonstrated antiproliferative activities in response to the five tested cell lines (IC50 = 4.09-16.82 μm). Compared with the positive control Nutlin-1, there was enhanced antiproliferative activity to p53-mutated or p53-deficient cell lines (SW620, HL60, and PC3).
authors.affiliation: College of Chemistry and Chemical Engineering, Shaoxing University, Shaoxing, 312000, China.
authors.forename: Chunqi
authors.initials: C
authors.lastname: Hu
authors.affiliation: College of Chemistry and Chemical Engineering, Shaoxing University, Shaoxing, 312000, China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Pharmacy, Zhejiang Medical College, 481 Binwen Road, Hangzhou, 310053, China.
authors.forename: Wenting
authors.initials: W
authors.lastname: Du
mesh_terms: D005454:Fluorescence Polarization; D062105:Molecular Docking Simulation; D066244:Proton Magnetic Resonance Spectroscopy; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D011720:Pyrazoles
keywords: anticancer; molecular docking; p53-MDM2; pyrazole derivatives; synthesis