Synthesis, characterization, and pharmacological evaluation of some novel thiadiazoles and thiazoles incorporating pyrazole moiety as anticancer agents

Abstract

Two series of novel 2-[[1-(5-methyl-1-phenyl-5-substituted-1H-pyrazol-4-yl)ethylidene]hydrazono]-3-phenyl-2,3-dihydro-1,3,4-thiadiazole derivatives and 2-[5-(4-chlorophenyl)-5′-methyl-1′-phenyl-3,4-dihydro-1′H,2H-[3,4′-bipyrazol]-2-yl]-4-substituted-5-(phenyldiazenyl)thiazole derivatives were prepared from reaction of hydrazonoyl halides with methyl 2-[1-(5-methyl-1-phenyl-1H-pyrazol-4-yl)ethylidene]hydrazine-carbodithioate and thiosemicarbazide derivative, respectively. The newly synthesized derivatives were elucidated by elemental analysis, spectral data, and alternative synthetic routes, whenever possible. The anti-cancer activity of the selected products against the breast carcinoma cell line MCF-7 was determined by WST-1 assay indicating concentration-dependent cellular growth inhibitory effect especially for three compounds with dose response curves indicating IC ₅₀ values of 21.3 ± 0.72, 21.3 ± 0.72, and 23.56 ± 0.81 µg cm⁻³, respectively. Confocal laser scanning imaging of the treated cells stained by rhodamin 123 and acridine orange dyes confirms that the selected compounds inhibit the mitochondrial lactate dehydrogenase enzymes. The obtained results revealed promising anticancer activity.

Graphical abstract