Synthesis and cytotoxic activity of novel 3-(1H-indol-3-yl)-1H-pyrazole-5-carbohydrazide derivatives

A series of novel 3-(1H-indole-3-yl)-1H-pyrazole-5-carbohydrazide derivatives 4Ia–n, 4IIa–b and 6 were prepared by hydrazinolysis of ethyl 3-(1H-indole-3-yl)-1H-pyrazole-5-carboxylate with hydrazine hydrate in excellent yields. These new compounds were fully characterized by spectroscopic methods, and the important intermediates 3Ie, 3IIc and 3IId were further confirmed by X-ray crystallography. All the new compounds were evaluated for their cytotoxic activity against 4 human cancer cell lines by MTT method. Some of them exhibited more potent antiproliferative activity against HepG-2, BGC823 and BT474 cell lines than the positive drug 5-fluorourcail. Flow cytometry analysis showed that 4Ik and 4Il arrested the cell cycle at S phase.

A series of novel 3-(1H-indole-3-yl)-1H-pyrazole-5-carbohydrazide derivatives were synthesized, characterized and evaluated for their cytotoxic activity against A549, HepG-2, BGC823 and BT474 cell lines in vitro by the MTT assay. Figure optionsDownload as PowerPoint slideHighlights
► 17 novel 3-(1H-indole-3-yl)-1H-pyrazole-5-carbohydrazide derivatives were synthesized and characterized.
► Compound 4Im was 52-fold more potent than 5-Fu against BT474 with IC50 value of 1.39 μM.
► Compound 4Ig was 8.6-fold more potent than 5-Fu against BGC823 cell with IC50 value of 0.71 μM.
► Compounds 4Ik showed the highest potency against HepG-2 with IC50 value of 1.32 μM.
► The cell cycle analysis revealed that 4Ik and 4Il arrested the HepG-2 cell cycle at S phase.