Synthesis and biological evaluation of bengacarboline derivatives.
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.
Pouilhès
Annie
A
Laboratoire de Chimie des Procédés et des Substances Naturelles, ICMMO, UMR8182, Université de Paris-sud 11, 91405 Orsay, France.
Kouklovsky
Cyrille
C
Langlois
Yves
Y
Baltaze
Jean-Pierre
JP
Vispé
Stéphane
S
Annereau
Jean-Philippe
JP
Barret
Jean-Marc
JM
Kruczynski
Anna
A
Bailly
Christian
C
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002243:Carbolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008386:Marine Biology; D015394:Molecular Structure; D059005:Topoisomerase II Inhibitors; D014561:Urochordata / Q000737:chemistry
D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D002243:Carbolines; D059005:Topoisomerase II Inhibitors; C527225:bengacarboline