155200-63-8Relevant academic research and scientific papers
Synthesis, antitumour activity and structure-activity relationships of 5H-benzo[b]carbazoles
Asche, Christian,Frank, Walter,Albert, Antje,Kucklaender, Uwe
, p. 819 - 837 (2007/10/03)
A series of novel 5H-benzo[b]carbazoles related to the ellipticines was obtained from the reactions of p-benzoquinones with 2-aminomethylene-1- indanones. Most of the compounds were evaluated for their antitumour activity in the National Cancer Institute's in vitro human tumour cell line screening panel. Among them, particularly derivative 15c bearing a p-quinone methide moiety in ring C of the heterocycle was found to show in vitro activity comparable to clinically well established anticancer agents such as amsacrine or mitomycin C. Compounds 9d, 9e and 12k showed increased potency to distinct cell lines like the leukemia or melanoma subpanel of cell lines. Based on the test results, structure-activity relationships for this series of compounds were developed. For instance, it was found that a quinonoid substructure in ring C leads to a noticeable increase in activity. The same observation was made for a 2-hydroxyl substituent at the ring system. 2-Acetoxy and 2-methoxy derivatives as well as 2-unsubstituted 5H-benzo[b]carbazoles either had a decreased potency or were found to be inactive. A COMPARE analysis with some of these compounds showed poor or no correlation with anticancer drugs of the NCI's standard agents database indicating a novel mechanism of action. Additionally, UV-vis titrations in the series of 5H-benzo[b]carbazoles indicated interactions with calf thymus DNA only for the highly active quinone methide 15c.
DNA intercalators. 1. Development of 2-hydroxy-benzo(b)carbazole derivatives as cytostatics
Kucklaender,Pitzler,Kuna
, p. 137 - 142 (2007/10/02)
Reaction of p-benzoquinone 3 and aminomethylene indanones 2 via easily oxidized benzocarbazoles 4/5 affords the heterocyclic quinones 6. The structure of 4/5 and 6 is proven by derivatization to 7b and 8b. The product 9 obtained by methylation of 6 is hydrogenated to 10 or debenzylated to 11. Ether cleavage yields 12. Reaction of 9 with lithium-methyl or NaBH4 affords 13 and the intermediates 14 and 15. Phenol 6a was alkylated to 16 or aminomethylated to 17 or 18. The indole quinones 17 and 18 show strong cytotoxic activity against colon cells and pulmonary carcinoma cells.
