title: Synthesis and antitumor activity of β-carboline 3-(substituted-carbohydrazide) derivatives.
abstract: A series of β-carboline derivatives bearing a substituted-carbohydrazide moiety at C-3 were synthesized and evaluated for their antitumor activity against eight human cancer cell lines. The β-carboline N-(substituted-benzylidene)carbohydrazides showed, in general, a greater antitumor activity than their N-(alkylidene)carbohydrazide analogues. The N(9)-methylation of β-carboline N-(substituted-benzylidene) carbohydrazides resulted in a decrease of antitumor activity. Among compounds tested, the benzylidene-carbohydrazides 3, 4, 11, 13, 16, 21 and 22 were the most active, possessing IC(50) less than 10 μM for six of the eight tumor cell lines assayed. The derivative 4 displayed the most significant activity toward all tested cell lines, with a remarkable cytotoxicity against renal (786-0) cell lines (IC(50)=0.04 μM). Compound 4 was assayed for its in vivo antineoplastic activity in the Ehrlich solid carcinoma assay.
authors.affiliation: Departamento de Química, UEM, Universidade Estadual de Maringá, 87020-900 Maringá, PR, Brazil.
authors.forename: Valéria Aquilino
authors.initials: VA
authors.lastname: Barbosa
authors.forename: Anelise S Nazari
authors.initials: AS
authors.lastname: Formagio
authors.forename: Franciele Cristina
authors.initials: FC
authors.lastname: Savariz
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Foglio
authors.forename: Humberto Moreira
authors.initials: HM
authors.lastname: Spindola
authors.forename: João Ernesto
authors.initials: JE
authors.lastname: de Carvalho
authors.forename: Emerson
authors.initials: E
authors.lastname: Meyer
authors.forename: Maria Helena
authors.initials: MH
authors.lastname: Sarragiotto
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002243:Carbolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D021241:Spectrometry, Mass, Electrospray Ionization; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D002243:Carbolines