Original scientific paper

https://doi.org/10.2478/acph-2013-0004

Synthesis and anti-tumor evaluation of novel hydrazide-hydrazone derivatives

WAGNAT WAHBA WARDAKHAN ; National Organization for Drug Control & Research P.O. 29 Cairo, A. R. Egypt
NAHED NASSER EL-SAYED ; National Organization for Drug Control & Research P.O. 29 Cairo, A. R. Egypt; College of Science, Department of Chemistry, King Saud University, Women Students –Medical Studies & Science Sections, P.O. Box 22452, Riyadh 11495, Kingdom of Saudi Arabia
RAFAT MILAD MOHAREB ; Department of Chemistry, Faculty of Science, Cairo University, Giza, A. R. Egypt

Abstract

The reaction of cyclopentanone with cyanoacetylhydrazine gave the 2-cyano-2-cyclopentylideneacetohydrazide (1). Treatment of compound 1 with elemental sulphur in the presence of triethylamine afforded the 2-amino-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbohydrazide (2) which in-turn formed the corresponding intermediate diazonium salt. The latter was coupled with either ethyl cyanoacetate or ethyl acetoacetate to form the 2-cyano-2-(3-(hydrazinecarbonyl)-5,6-dihydro-4H-cyclopenta[b]thiophen-2-yl)hydrazono)acetate (3) and ethyl 2-(2-(3-(hydrazinecarbonyl)-5,6-dihydro-4H-cyclopenta[b]thiophen-2-yl)hydrazono)-3-oxobutanoate (4), respectively. On the other hand, the reaction of compound 1 with either benzaldehyde or acetophenone afforded N'-benzylidene-2-cyano-2-cyclopentylideneacetohydrazide (7) and 2-cyano-2-(2-cyclopentylidene)phenylacetohydrazide (10), respectively. Moreover, compound 1 was used to synthesise the 2-cyano-2-cyclopentylidene-N'-(arylthiazol-2(3H)-ylidene)acetohydrazides 6a,b, 2-(2-benzylidenecyclopentylidene)-2-cyanoacetohydrazide (8), 2-amino-N'-benzylidene-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbohydrazide (9), 2-cyano-2-(2-(2-phenylhydrazono)cyclopentylidene)acetohydrazide (11), N'-(1-chloropropan-2-ylidene)-2-cyano-2-cyclopentylideneacetohydrazide (12), and the 2-cyclopentylidene-3-(3,5-disubstituted-1H-pyrazol-1-yl)-3-oxopropanenitriles 13a,b through its reaction with the respective reagents. The antitumor evaluation of the newly synthesized compounds against the three human tumor cells lines, namely breast adenocarcinoma (MCF-7), non-small cell lung cancer (NCI-H460) and CNS cancer (SF-268) showed that some of the described compounds exhibit higher inhibitory effects towards the three tumor cell lines than the reference compound doxorubicin.

Keywords

hydrazide; hydrazide-hydrazone; thiophene; pyrazole; antitumor

Hrčak ID:

96018

URI

https://hrcak.srce.hr/96018

Publication date:

31.3.2013.

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