title: Studies on the cytotoxic activity of synthetic 2H-azirine-2-azetidinone compounds.
abstract: 2-azetidinones and 2H-azirines show antibacterial and cytotoxic activities, however the biological properties of molecules containing both 2H-azirine and 2-azetidinone functions in the same structure had never been evaluated before. In the present study, two 2H-azirine-2-azetidinones (1 and 2) and three 2H-azirines (3-5) were synthesized from 2-formyl-3-phenyl-2H-azirine-N-arylimines with diphenylketene. The compounds were assayed for antibacterial and cytotoxic activities. None of them showed antibacterial activity on the tested strains, but both 2H-azirine-2-azetidinones showed cytotoxicity against four tumor cell lines (HL-60, leukemia; HCT-8, colon cancer; MDA-MB-435, melanoma; and SF-295, CNS). The IC(50) values of 1 ranged from 1.1 to 10.5 microM and from 3.8 to 26.6 microM for 2. The mechanism of cell growth inhibition of 1 and 2 towards HL-60 cell line was also investigated. Membrane damage, cell viability, DNA synthesis inhibition and morphological changes were evaluated. The preliminary findings suggested that 1 and 2 induce apoptosis.
authors.affiliation: Centro de Ciências da Saúde, Universidade de Fortaleza, Fortaleza, Ceará, Brazil.
authors.forename: Daniel Pinheiro
authors.initials: DP
authors.lastname: Maia
authors.forename: Diego Veras
authors.initials: DV
authors.lastname: Wilke
authors.forename: Jair
authors.initials: J
authors.lastname: Mafezoli
authors.forename: José Nunes
authors.initials: JN
authors.lastname: da Silva Júnior
authors.forename: Manoel Odorico
authors.initials: MO
authors.lastname: de Moraes
authors.forename: Claudia
authors.initials: C
authors.lastname: Pessoa
authors.forename: Letícia Veras
authors.initials: LV
authors.lastname: Costa-Lotufo
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001384:Azetidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D001384:Azetidines