Microwave-assisted synthesis of a fluorinated pyrazoline, in silico study and in vitro cytotoxic evaluation against HeLa cell line

Abstract

Pyrazoline analogues have been reported with some significant biological activities, such as anticancer, antidiabetic and antimalarial. In this work, a fluorinated pyrazoline analogue, 5-(4-fluorophenyl)-3-(naphthalen-1-yl)-4,5-dihydro-1H-pyrazole (Compound 3) has been synthesized under microwave irradiation. The structure of synthesized compound was confirmed based on the spectroscopic data i.e. UV, FT-IR, GCMS, and 1H NMR. Based on the in silico study, the synthesized compound possessed a potent inhibitory activity against human thymidilate synthase (hTS) (PDB ID 4E28). The docking results of the pyrazoline analogue to this enzyme showed the binding free energy of -4.4397 kcal/mol and it is lower than 5-fluorouracil (5-FU) used as reference for anticancer drug (-2.2774 kcal/mol). In addition, the result of in vitro cytotoxic evaluation showed that the synthesized compound exhibited a strong cytotoxic activity against HeLa cell line with IC50 value of 27.56 μg/ml. The result of both in silico and in vitro evaluations suggests that the compound 3 might be a promising agent for cervical cancer treatment.