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Acta Pharmaceutica

The Journal of Croatian Pharmaceutical Society

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CiteScore 2016: 1.55

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Volume 63, Issue 1


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

Wagnat Wahba Wardakhan / El-Sayed Nahed Nasser Eid
  • National Organization for Drug Control and Research P.O. 29 Cairo, A. R. Egypt
  • 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
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Rafat Milad Mohareb
Published Online: 2013-03-12 | DOI: https://doi.org/10.2478/acph-2013-0004

The reaction of cyclopentanone with cyanoacetylhydrazine gave 2-cyano-2-cyclopentylideneacetohydrazide (1). Treatment of compound 1 with elemental sulphur in the presence of triethylamine afforded 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 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 synthesize 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 2-cyclopentylidene-3- -(3,5-disubstituted-1H-pyrazol-1-yl)-3-oxopropanenitriles (13a,b) through its reaction with the respective reagents. 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 exhibited higher inhibitory effects towards the three tumor cell lines than the reference compound doxorubicin.

Keywords: hydrazide; hydrazide-hydrazone; thiophene; pyrazole; antitumor

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About the article

Published Online: 2013-03-12

Published in Print: 2013-03-01

Citation Information: Acta Pharmaceutica, Volume 63, Issue 1, Pages 45–57, ISSN (Online) 1846-9558, ISSN (Print) 1330-0075, DOI: https://doi.org/10.2478/acph-2013-0004.

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