In vitro Anti Leukemia Cancer Activity of Some Novel Pyrazole Derivatives and Pyrazoles Containing Thiazole Moiety

Abstract

The design and syntheses of several novel pyrazole derivatives (2, 5, 6 and 7) and pyrazole derivatives (3 and 4) containing thiazole moiety via by ethyl β-(p-chlorophenyl)–α-cyanoacrylate (1) and thiosemicarbazide as starting materials. Pyrazole derivatives (3 and 4) containing thiazole moiety were synthesized via cyclization of pyrazole derivative (2) with bromomethyl arylketones, to give compound 3, followed by acetylation. N- (3- methoxy-2-hydroxybenzal) -3- (p- chlorophenyl)-4- cyano-5-oxopyrazol-1-thiocarboxamide (6) was synthesized via reaction of compound 2 with 3-methoxy-2- hydroxybenzaldehyde. Structures of all compounds were confirmed by elemental analysis, FT-IR, 1H-NMR, 13C-NMR and mass spectrometry. The cytotoxic activity of all the synthetic compounds were evaluated against Leukemia HL-60 compared with Doxorubicicn. The cytotoxic activity was checked in vitro for the recently prepared compounds by using the MTT assay. Compounds 4, 6 and 9 were the most active against Leukemia HL-60. The IC50 values of them were less than 5 µM in the range of 1.35-4.78 µM. In addition, compounds 3 and 5 showed less antiproliferative activity against Leukemia HL-60 cells with IC50 values in the range 5.39-8.82 µM. Compound 6 was the most potent cytotoxic activity. The studies biological activity includes cell cycle analysis, apoptosis detection assay and Topoisomerase II inhibition activity assay explained that compound 6 is a strong Topo II inhibitor.