Synthesis and biological evaluation of bengacarboline derivatives

• Published in: Bioorganic & medicinal chemistry 2008-02, Vol.18 (3), p.1212-1216
• Main Authors: Pouilhès, Annie, Kouklovsky, Cyrille, Langlois, Yves, Baltaze, Jean-Pierre, Vispé, Stéphane, Annereau, Jean-Philippe, Barret, Jean-Marc, Kruczynski, Anna, Bailly, Christian
• Format: Article
• Language: English
• Subjects: Alkaloids - chemical synthesis; Alkaloids - chemistry; Alkaloids - pharmacology; Animals; Antineoplastic Agents, Phytogenic - chemical synthesis; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis - drug effects; Apoptosis - physiology; Bengacarboline; Biological and medical sciences; Carbolines - chemical synthesis; Carbolines - chemistry; Carbolines - pharmacology; Cell Cycle - drug effects; Cytotoxicity; DNA Damage - drug effects; DNA damages; Drug Screening Assays, Antitumor; Humans; Indole; Marine alakaloid; Marine Biology; Medical sciences; Miscellaneous; Molecular Structure; Pharmacology. Drug treatments; Topoisomerase II Inhibitors; Urochordata - chemistry
• ISSN: 0960-894X; 0968-0896; 1464-3405; 1464-3391
• DOI: 10.1016/j.bmcl.2007.11.113

Bengacarboline derivatives ( 11– 13 and 15) were synthesized. Seco derivatives 11 and 12 display a cytotoxic activity by inducing an accumulation of cells in the S phase of DNA synthesis Novel derivatives of the marine alkaloid bengacarboline have been synthesized. The seco derivatives 11 and 12 were evaluated for topoisomerase inhibition, DNA damages, cytotoxicity and cell cycle perturbation. The two synthetic analogs are more potent cytotoxic agents than bengacarboline and they both induce an accumulation of cells in the S phase of DNA synthesis. They do not function as topoisomerase inhibitors but trigger DNA damages in cells.