Synthesis, Crystal Structure and Evaluation of Cancer Inhibitory Activity of 4-[indol-3-yl-Methylene]-1H-pyrazol-5(4H)-one derivatives

Abstract

A series of 4-(1 H-indol-3-yl-methylene)-1 H-pyrazol-5(4 H)-one derivatives have been synthesised. The Z structure of 4-[(1-methyl-1 H-indol-3-yl)methylene]-3-phenyl-1 -p-tolyl-1 H-pyrazol-5-one was determined by X-ray crystallography. The antitumour activity was evaluated against five cancer cells by MTT assay. [(1 H-Indol-3-yl)methylene]-1-(2,4-dini-trophenyl)-3-methyl-1 H-pyrazole-5-one and 4-{4-[(1-benzyl-1 H-indol-3-yl)methylene]-3-methyl-5-oxo-4,5-dihydro-1 H-pyrazol-1-yl}-benzoic acid have similar anticancer activity with 5-UF on the test cancer cells (exception of A375). Almost all the target compounds displayed antitumour activity against A549 and PC-9, and those with benzyl at 1-position of indole had higher activity against PC-9 (IC50 value lower than 30 μM). Those with benzyl at the indole and carboxyl at the phenyl part of of pyrazole were more active against PC-9 and A549 cells, providing a good indication for subsequent optimisation as lung cancer inhibitory agents.