title: Synthesis and anti-tumor evaluation of novel hydrazide and hydrazide-hydrazone derivatives.
abstract: 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.
authors.affiliation: National Organization for Drug Control and Research P.O. 29 Cairo, A. R. Egypt. wagnatward@hotmail.com
authors.forename: Wagnat Wahba
authors.initials: WW
authors.lastname: Wardakhan
authors.forename: Nahed Nasser Eid
authors.initials: NN
authors.lastname: El-Sayed
authors.forename: Rafat Milad
authors.initials: RM
authors.lastname: Mohareb
mesh_terms: D000098:Acetophenones / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001547:Benzaldehydes / Q000737:chemistry; D001932:Brain Neoplasms / Q000188:drug therapy; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D045744:Cell Line, Tumor; D003979:Diazonium Compounds / Q000737:chemistry; D004317:Doxorubicin / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D006801:Humans; D006834:Hydrazines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D006835:Hydrazones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D061986:MCF-7 Cells; D011720:Pyrazoles / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000098:Acetophenones; D000970:Antineoplastic Agents; D001547:Benzaldehydes; D003979:Diazonium Compounds; D006834:Hydrazines; D006835:Hydrazones; D011720:Pyrazoles; C031280:pyrazole; D004317:Doxorubicin; C038699:acetophenone; C032175:benzaldehyde; C019289:carbohydrazide