Design and synthesis of de novo cytotoxic alkaloids through mimicking taxoid skeleton.
Based on a common pharmacophore model and the hypothesis that the baccatin core of taxoids is a scaffold securing the proper orientation of the side chains, a bicyclic alkaloid scaffold was designed as a baccatin surrogate. Using this scaffold, two novel macrocyclic and open-chain 'taxoid-mimicking' compounds were synthesized. Two of these 'taxoid-mimics', 2 and 3, were found to possess cytotoxicity with micromolar level IC50 values against human breast cancer cell lines.
Geng
Xudong
X
Department of Chemistry, State University of New York at Stony Brook, Stony Brook, NY 11794-3400, USA.
Geney
Raphaël
R
Pera
Paula
P
Bernacki
Ralph J
RJ
Ojima
Iwao
I
D000470:Alkaloids / Q000138:chemical synthesis* / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000494:pharmacology; D001643:Bridged Bicyclo Compounds / Q000737:chemistry; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D008968:Molecular Conformation; D018716:Molecular Mimicry; D013329:Structure-Activity Relationship; D043823:Taxoids / Q000737:chemistry* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D001643:Bridged Bicyclo Compounds; D043823:Taxoids