Novel 1-((benzoimidazole-2-yl)methyl)-3-phenyl- 1,4-dihydropyrazole-5-one and their derivatives: Synthesis and preliminary cytotoxicity test as anti-breast cancer

This work presented synthesis of new pyrazolone derivatives and their cytotoxicity assay. The synthesis of pyrazolone derivatives have been achieved using condensation of 2-hydrazinyl methyl-1H-benzoimidazole (H1) with ethylbenzoylacetate in presence of ethanol, which in turn, yielded 1-(benzoimidazole-2-yl)methyl-3-phenyl-1, 4-dihydropyrazole-5-one (BPP). Then, it has reacted with diazonium solution in ethanol and benzoyl chloride in hot dioxin to give 4-azo pyrazolone (BMPAP) and 4-acyl pyrazolone (BMPBP) respectively. The newly synthesized compounds were characterized by FT-IR, 1H NMR and13C NMR. The cytotoxicity assay of the BPP, BMPAP and BMPBP on human breast cancer cells (MCF7) demonstrated their killing ability similar with naturally occurring toxins or immune-mediator cells. The cytotoxicity test was performed using MTT assay (3-[4, 5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide). Cell culture with the concentration of 2�104 cells/ml was prepared and was plated (100 �l/well) onto 96-well plates. The diluted ranges of sample extracts were added to each well with identified concentrations: 100, 50, 25, 12.5, 6.25, 3.13 and 1.56 �g/ml and then incubated for 72 hr. MTT solution was added at the end of incubation samples to the cells and continued further for incubation in 3 hr. After solubilization of the purple formazan crystals using DMSO were completed, the Optical Density (OD) was measured using an ELISA reader at a wavelength of 570 nm. The cytotoxicity was recorded as the drug concentration causing 50% growth inhibition of the tumor cells (IC50 value). Overall cytotoxicity test was varied between pyrazolone derivatives with 50% or higher inhibition below 27 �g/ml, and it was considered active and potentially target for further screening. � 2017 American Scientific Publishers All rights reserved.