Studies on the cytotoxic activity of synthetic 2H-azirine-2-azetidinone compounds

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• 作者：Daniel Pinheiro Maia ; Diego Veras Wilke ; Jair Mafezoli ; José ; Nunes da Silva Jú ; nior ; Manoel Odorico de Moraes ; Claudia Pessoa ; Letí ; cia Veras Costa-Lotufo
• 关键词：2H-azirine-2-azetidinone ; Cytotoxicity ; Apoptosis ; HL-60 cells
• 刊名：Chemico-Biological Interactions
• 出版年：2009
• 出版时间：15 July 2009
• 年：2009
• 卷：180
• 期：2
• 页码：220-225
• 全文大小：824 K

文摘

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 IC₅₀ values of 1 ranged from 1.1 to 10.5 μM and from 3.8 to 26.6 μM 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.