Synthesis and antitumoral activity of novel thiazolobenzotriazole, thiazoloindolo[3,2-c]quinoline and quinolinoquinoline derivatives.
The biological evaluation of some novel thiazoloindolo[3,2-c]quinoline, 8-substituted-11H-indolo[3,2-c]quinolines is described. These compounds were obtained via Graebe-Ullmann thermal cyclization from appropriated N-arylated benzotriazoles. 7H-4,7-Diaza-benzo[de]anthracene, a reaction by-product structurally closed to the pyridoacridine skeleton was also identified. All thiazolobenzotriazole intermediates were tested in vitro for their capacity to inhibit the growth of two breast cancer cell lines, MCF-7 and MDA-MB-231. In parallel, the newly synthesized skeletons were evaluated for DNA interaction, topoisomerases' inhibition, and cytotoxicity against HL60 and HL60/MX2 human leukemia cells. Most compounds showed a potent growth inhibitory effect on all the tested cell lines, with IC(50) in the muM range.
Université de La Rochelle, UMR CNRS 6250 LIENSs, Equipe Molécules à Activités Biologiques, Avenue Michel Crépeau, 17042 La Rochelle, France.
Anne
A
Beauchard
Alexis
A
Jaunet
Laurence
L
Murillo
Brigitte
B
Baldeyrou
Amélie
A
Lansiaux
Jean-René
JR
Chérouvrier
Lisianne
L
Domon
Laurent
L
Picot
Christian
C
Bailly
Thierry
T
Besson
Valérie
V
Thiéry
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D005260:Female; D006801:Humans; D007211:Indoles / Q000737:chemistry; D007938:Leukemia / Q000188:drug therapy; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D013844:Thiazoles / Q000737:chemistry; D059004:Topoisomerase I Inhibitors; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity
D000970:Antineoplastic Agents; D007211:Indoles; D011804:Quinolines; D013844:Thiazoles; D059004:Topoisomerase I Inhibitors; D014230:Triazoles; C012771:benzotriazole; D004247:DNA; C427203:calf thymus DNA; D004264:DNA Topoisomerases, Type I