Synthesis and anti-proliferative activity of a small library of 7-substituted 5H-pyrrole [1, 2-a][3, 1]benzoxazin-5-one derivatives. Issue 14 (15th July 2017)

• Record Type: Journal Article
• Authors: Badolato, Mariateresa; Carullo, Gabriele; Armentano, Biagio; Panza, Salvatore; Malivindi, Rocco; Aiello, Francesca
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 14(2017)
• Page Start: 3092
• Page End: 3095
• Publication Date: 2017-07-15
• Subjects: Benzoxazin-5-one -- Anti-proliferative activity -- Suzuki-Miyaura cross coupling -- Cell cycle analysis -- Cancer cell lines; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.05.046
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Highlights: 5 H -pyrrolo [1, 2- a ][3, 1]benzoxazin-5-one is an interesting scaffold. Various decorations have been performed to find an anti-proliferative agents. Preliminary studies identified3b a good candidate. The mechanism of action will be investigated. Abstract: In this study, we investigate the anti-proliferative activity of a small library of 7-substituted 5 H -pyrrolo[1, 2- a ][3, 1]benzoxazin-5-one derivatives, against a panel of human cancer cell lines. We reported the synthesis of these compounds in a previous work. 7-Bromo-5 H -benzo[ d ]pyrrolo[2, 1- b ][1, 3]oxazin-5-one showed a promising anti-proliferative effect. As starting material for Suzuki-Miyaura cross coupling reaction, it was selected for the design and the synthesis of six further derivatives, with the aim to better define structure-activity relationships. The anti-proliferative MTT assay revealed a dose-dependent reduction of cell viability, especially for 7-([1, 1′-biphenyl]-4-yl)-5 H -benzo[ d ]pyrrolo[2, 1- b ][1, 3]oxazin-5-one. Cell cycle and western blotting analysis suggested apoptosis as possible mechanism for its anti-proliferative activity. These preliminary results encourage our interest for further optimizations.