1,2,3-triazole analogs of combretastatin A-4 as potential microtubule-binding agents.
A series of cis-restricted 1,4- and 1,5-disubstituted 1,2,3-triazole analogs of combretastatin A-4 (1) have been prepared. Cytotoxicity and tubulin inhibition studies showed that 2-methoxy-5-((5-(3,4,5-trimethoxyphenyl)-1H-1,2,3-triazol-1-yl)methyl)aniline (5e) and 2-methoxy-5-(1-(3,4,5-trimethoxybenzyl)-1H-1,2,3-triazol-5-yl)aniline (6e) were two of the most active compounds. Molecular modeling studies revealed that the N-2 and N-3 atoms in the triazole rings in 5e and 6e did not form hydrogen bonds with the amino acids in the anticipated pharmacophore.
Odlo
Kristin
K
School of Pharmacy, Department of Pharmaceutical Chemistry, University of Oslo, PO Box 1068, N-0316 Oslo, Norway.
Fournier-Dit-Chabert
Jérémie
J
Ducki
Sylvie
S
Gani
Osman A B S M
OA
Sylte
Ingebrigt
I
Hansen
Trond Vidar
TV
D000814:Aniline Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D001665:Binding Sites; D045744:Cell Line, Tumor; D003198:Computer Simulation; D006801:Humans; D008870:Microtubules / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D013267:Stilbenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity
C554533:2-methoxy-5-((5-(3,4,5-trimethoxyphenyl)-1H-1,2,3-triazol-1-yl)methyl)aniline; C554534:2-methoxy-5-(1-(3,4,5-trimethoxybenzyl)-1H-1,2,3-triazol-5-yl)aniline; D000814:Aniline Compounds; D013267:Stilbenes; D014230:Triazoles; D050257:Tubulin Modulators; C058728:fosbretabulin