title: Novel benzimidazole derivatives as expected anticancer agents.
abstract: A series of 1-(1H-benzimidazol-2-yl)-3-(substituted)-2-propen-1-one and its 1-methyl analogues 2c-h were synthesized and cyclized with different reagents such as ethyl cyanoacetate, thiourea, hydroxylamine hydrochloride, guanidinium sulfate, methylhydrazine, phenylhydrazine and/or hydrogen peroxide in different reactions to produce pyridones 3a,b, pyrimidinethione 4a,b, isoxazole 5a,b, aminopyrimidine 6a,b, pyrazoline 7i-k and epoxy derivative 8, respectively. Acetohydrazide 10 reacted with formic acid, acetic anhydride, carbon disulfide and/or thiosemicarbazide to yield compounds 11-19. Also compound 21a,b was condensed with different monosaccharides to yield the corresponding N-glycoside Schiff's bases derivatives 22a-h, which upon treatment with acetic anhydride afforded 23a-h derivatives. The anticancer activity of some of the newly synthesized compounds was evaluated against HEPG2 (human liver carcinoma cell line) and PC12 (pheochromocytoma of the rat adrenal medulla) cells. Benzimidazole-2-isoxazole 5a derivative exhibited high potency against HEPG2 and PC12 cells. Benzimidazole chalcones 2c,e, benzimidazole mercaptoacetohydrazide 14 and benzimidazole thiosemicarbazide 15a,b derivatives gave high potency against PC12 cells.
authors.affiliation: Therapeutical Chemistry Department, National Research Centre, Dokki, Cairo, Egypt. dr.zmnofal@yahoo.com
authors.forename: Zienab M
authors.initials: ZM
authors.lastname: Nofal
authors.forename: Elsyed A
authors.initials: EA
authors.lastname: Soliman
authors.forename: Somaia S
authors.initials: SS
authors.lastname: Abd El-Karim
authors.forename: Magdy I
authors.initials: MI
authors.lastname: El Zahar
authors.forename: Aladdin M
authors.initials: AM
authors.lastname: Srour
authors.forename: Shalini
authors.initials: S
authors.lastname: Sethumadhavan
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Maher
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology; D015394:Molecular Structure; D016716:PC12 Cells; D010673:Pheochromocytoma / Q000473:pathology; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001562:Benzimidazoles