title: Synthesis and antitumor activity of novel 1-substituted phenyl 3-(2-oxo-1,3,4-oxadiazol-5-yl) β-carbolines and their Mannich bases.
abstract: A series of novel 1-(substituted phenyl)-3-(2-oxo-1,3,4-oxadiazol-5-yl) β-carbolines (4a-e) and the corresponding Mannich bases 5-9(a-c) were synthesized and evaluated for their in vitro antitumor activity against seven human cancer cell lines. Compounds of 4a-e series showed a broad spectrum of antitumor activity, with GI50 values lower than 15μM for five cell lines. The derivative 4b, having the N,N-dimethylaminophenyl group at C-1, displayed the highest activity with GI50 in the range of 0.67-3.20μM. A high selectivity and potent activity were observed for some Mannich bases, particularly towards resistant ovarian (NCI-ADR/RES) cell lines (5a, 5b, 6a, 6c and 9b), and ovarian (OVCAR-03) cell lines (5b, 6a, 6c, 9a, 9b and 9c). In addition, the interaction of compound 4b with DNA was investigated by using UV and fluorescence spectroscopic analysis. These studies indicated that 4b interact with ctDNA by intercalation binding.
authors.affiliation: Departamento de Química, Universidade Estadual de Maringá, Av. Colombo, 5790, CEP: 87020-900 Maringá, PR, Brazil.
authors.forename: Franciele Cristina
authors.initials: FC
authors.lastname: Savariz
authors.affiliation: Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas (CPQBA), Universidade Estadual de Campinas, 6171, CEP: 13083-970 Campinas, SP, Brazil.
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Foglio
authors.affiliation: Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas (CPQBA), Universidade Estadual de Campinas, 6171, CEP: 13083-970 Campinas, SP, Brazil.
authors.forename: Ana Lucia T Goes
authors.initials: AL
authors.lastname: Ruiz
authors.affiliation: Departamento de Química, Universidade Estadual de Maringá, Av. Colombo, 5790, CEP: 87020-900 Maringá, PR, Brazil.
authors.forename: Willian Ferreira
authors.initials: WF
authors.lastname: da Costa
authors.affiliation: Instituto de Química e Biotecnologia, Universidade Federal de Alagoas, Av. Lourival Melo Mota, s/n, Tabuleiro do Martins, CEP: 57072-970 Maceió, AL, Brazil.
authors.forename: Marina de Magalhães
authors.initials: Mde M
authors.lastname: Silva
authors.affiliation: Instituto de Química e Biotecnologia, Universidade Federal de Alagoas, Av. Lourival Melo Mota, s/n, Tabuleiro do Martins, CEP: 57072-970 Maceió, AL, Brazil.
authors.forename: Josué Carinhanha Caldas
authors.initials: JC
authors.lastname: Santos
authors.affiliation: Instituto de Química e Biotecnologia, Universidade Federal de Alagoas, Av. Lourival Melo Mota, s/n, Tabuleiro do Martins, CEP: 57072-970 Maceió, AL, Brazil.
authors.forename: Isis Martins
authors.initials: IM
authors.lastname: Figueiredo
authors.affiliation: Departamento de Química, Universidade Estadual de Maringá, Av. Colombo, 5790, CEP: 87020-900 Maringá, PR, Brazil.
authors.forename: Emerson
authors.initials: E
authors.lastname: Meyer
authors.affiliation: Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas (CPQBA), Universidade Estadual de Campinas, 6171, CEP: 13083-970 Campinas, SP, Brazil.
authors.forename: João Ernesto
authors.initials: JE
authors.lastname: de Carvalho
authors.affiliation: Departamento de Química, Universidade Estadual de Maringá, Av. Colombo, 5790, CEP: 87020-900 Maringá, PR, Brazil. Electronic address: mhsarragiotto@uem.br.
authors.forename: Maria Helena
authors.initials: MH
authors.lastname: Sarragiotto
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002243:Carbolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002417:Cattle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D053837:DNA Cleavage / Q000187:drug effects; D006801:Humans; D008352:Mannich Bases / Q000737:chemistry*; D010069:Oxadiazoles / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D002243:Carbolines; D008352:Mannich Bases; D010069:Oxadiazoles; D004247:DNA; C427203:calf thymus DNA
keywords: 2-Oxo-1,3,4-oxadiazole; Antitumor activity; Mannich bases; Synthesis; ctDNA interaction; β-Carboline