Acta Pharm. 63 (2013) 45-57

 

full paper

Original research paper

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

WAGNAT WAHBA WARDAKHAN, NAHED NASSER EID EL-SAYED and RAFAT MILAD MOHAREB

wagnatward@hotmail.com

1 National Organization for Drug Control and Research P.O. 29 Cairo, A. R. Egypt

2 College of Science, Department of Chemistry, King Saud University, Women Students Medical Studies and Science Sections, P.O. Box 22452, Riyadh 11495, Kingdom of Saudi Arabia

3 Department of Chemistry, Faculty of Science, Cairo University, Giza, A. R. Egypt

Accepted September 28, 2012

 

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