Convenient one-pot synthesis and biological evaluation of novel 3,5-dimethyl-1H-pyrazole-1-carbothiohydrazide derivatives as new anti-tumor agents against both liver carcinoma (HepG2) and lung carcinoma (A549) cell lines

Pyrazle constituents have garnered consideration mainly because of their presumed biological and curative properties. Therefore, the goal of the presented research is to create some novel pyrazole-1-carbothiohydrazide derivatives with predicted biological functions using an accessible one-pot synthesis employing 3,5-dimethyl-1H-pyrazole-1-carbothiohydrazide (1) as a facile antecedent. The component 1 and 1,3-diphenylpropane-1,3-dione (2) interacted resulting in pyrazole derivative 3 when ethanol or acetic acid were supplied. However, when the substance 1 interacted in ethanol with either 2 or acetyl acetone 5, using the catalytic proportion of triethylamine offered, it yielded compounds 4 and 6 respectively. Ingredient 1 was subjected to additional reactions with ethyl cyanoacetate (7), stearic acid 10, or equivalent carboxylic acids 12a-c, resulted in the formation of 9, 11, and 13a-c consequently. Additionally, when 1 was combined with α-haloketones 14 or 16, it yielded the corresponding 1,3,4-thiadiazine derivatives, 15 and 17. Every designed product's chemical structure was established according to spectroscopic and analytical results. The cytotoxic activities of the synthesized chemicals were assessed against two carcinoma cell lines, and compared to the standard drug Cisplatin using the colorimetric MTT assay. Furthermore, the results revealed that chemical 17 was the most active against the liver and lung carcinoma cell lines giving potent IC50 value of 5.35 and 8.74 μM, respectively, compared with reference drug cisplatin (3.78 and 6.39 μM). Interestingly, ingredient 17 when evaluated for their toxicity against normal lung fibroblast (MRC-5) cells exhibited low toxic effects indicating the safe use. Generally, our results exerted promising bioactive compounds.