NEW APPROACHES FOR THE SYNTHESIS OF HYDRAZONE DERIVATIVES AND THEIR ANTITUMOR EVALUATION

Abstract

The hydrazide-hydrazone 3 reacted with benzenediazonium chloride to give the phenylhydrazone derivative 5. The latter underwent a series of hetero- cyclization reactions to give pyridazine, 1,2,3-triazole and pyrazole derivatives. The antitumor evaluation of the newly synthesized products against the three cancer cells lines namely breast adenocarcinoma (MCF-7), non-small cell lung cancer (NCI-H460) and CNS cancer (SF-268) showed that some of them have higher inhibitory effects towards the three cell lines compared to the standard. Key word: hydrazide-hydrazone, pyridazine, 1,2,3-triazole, pyrazole, anti-tumor. activities. These observations led us to synthesize novel hydrazide-hydrazones and to investigate their possible antitumor activities. It has been reported in the literature 17,18 that hydrazide-hydrazones can give the corresponding hydrazide and aldehyde metabolites whereas the related hydrazides are known to yield carboxylic acids via hydrolytic route. Based on this knowledge, hydrazide-hydrazones derivative 3 was prepared easily from the reaction of cyanoacetyl hydrazine with benzaldehyde and subsequently used for the synthesis of pyridazine, 1,2,3-triazole and pyrazole derivatives. The newly synthesized compounds were tested to evaluate their in vitro anti-tumor activities against three human tumor cell lines representing different tumor types, namely, breast adenocarcinoma (MCF-7), non-small cell lung cancer (NCI-H460) and CNS cancer (SF-268). It was found that some of these compounds showed inhibitory effects on the three cell lines, indicating their potential use in the development of anti-cancer agents. group of compound 15 using sodium nitrite solution in the presence of acetic/ hydrochloric acids resulted in the formation of intermediate pyrazole-3- diazonium salt 16. Coupling of the latter diazonium salt with malononitrile in ethanol containing sodium acetate afforded the hydrazo derivative 17. The analytical and spectral data of the obtained product were consistence with the proposed structure (Scheme 2).