One-Pot Synthesis and Anticancer Activity of Novel Pyrazole Hybrids

Abstract

Novel pyrazole hybrids (3-17) were synthesized via one-pot reaction of thiocarbonyldihydrazide (1), ethyl 3-phenyl-3-oxopropanoate (2), and different carbonyl reagents in good yields (68–98 %). Their structures were confirmed using IR, 1HNMR, 13CNMR, and Mass spectroscopy (MS), as well as elemental analysis. Pyrazole hybrids (3-17) were screened for their cytotoxicity against three different breast cancer cell lines (e. g., MDA-MB-231, MCF-7, and 4T1) and HepG2 liver cancer cells. Interestingly, 5-oxo-N′-(2-oxoindolin-3-ylidene)-3-phenyl-4,5-dihydro-1H-pyrazole-1-carbothiohydrazide (13) exhibited good anticancer activity (IC50=25±0.4 μM) against the aggressive, invasive, and tumorigenic 4T1 cells. Therefore, its therapeutic index was estimated in normal human skin fibroblast (HSF). Moreover, its possible mode of action was investigated using colony formation, wound healing, apoptosis induction, cell cycle, and DNA damage assays. Collectively, pyrazole 13 led to 4T1 cells cell death via inhibition of wound healing and colony formation as well as cell cycle delay in the G0/G1 phase, activation of p27 levels, and apoptosis probably via DNA intercalation.