Synthesis and molecular docking of 5-(2-fluorophenyl)-3-(naphthalene-1-yl)-1-phenyl-1H-pyrazole as potential anti-breast cancer agent

Abstract

Pyrazole is a heterocyclic azo-derived compound with various biological activities, such as anticancer, antimicrobial, antioxidant, and anti-inflammation. This research aims to synthesize a fluorophenyl-containing pyrazole derivative, verify its toxicity value and predict its anti-breast cancer activity. The compound 5-(2-fluorophenyl)-3- (naphthalene-1-yl)-1-phenyl-1H-pyrazole was with success synthesized in two steps. Initially, the pyrazoline was synthesized by a one-pot cyclized reaction and assisted by microwave irradiation. Then, pyrazole was synthesized via oxidative aromatization reaction of pyrazoline with glacial acetic acid under conventional heating. The activity was evaluated by molecular docking simulation of the synthesized compound against Estrogen Receptor α (PDB ID: 3ERT) using AutoDock 4.2.6.ERα is a receptor protein bound to the native ligand 4-OHT used as a breast cancer receptor. The structure of synthesized pyrazole derivative was predicted by ultraviolet (UV), Fourier Transform Infrared (FTIR), Gas Chromatography Mass Spectroscopy (GC-MS), 1D and 2D nuclear magnetic resonance (NMR) spectroscopy data analysis. Furthermore, the toxicity was evaluated by the Brine Shrimp Lethality Test (BSLT) for pre-screening of anticancer drugs analysis, showing that the compound was toxic with LC50 values of 49.07 µg/mL. The result of the molecular docking study, a replacement fluorinated pyrazole compound showed potential inhibition against ERα with binding affinity and Ki worth of -10.77 kcal/mol and 12.69 nM, respectively. Thus, the fluorinated pyrazole compound is a promising candidate as an anti-breast cancer agent through antagonist activity on ERα.