Synthesis and anti-cancer activity of C-ring-functionalized prodigiosin analogues.
Prodigiosin is the parent member of the 4-methoxypyrrolyldipyrromethene family of natural products and is known for its anti-cancer activity. A new series of analogues was synthesized, incorporating pendent functional esters and beta-carbonyl substituents on the C-ring. The beta-carbonyl group allowed for the facile isolation of the prodigiosenes, and the pendent esters allow for further derivatization. The novel prodigiosenes generally retain the anti-cancer activity of prodigiosin in 60 human cell lines derived from nine cancer cell types, with neither the conjugated beta-carbonyl group, as either ketone or ester, nor the pendent ester significantly reducing the anti-cancer activity of the core skeleton.
Regourd
Jasmine
J
Department of Chemistry, Dalhousie University, Halifax, Nova Scotia B3H 4J3, Canada.
Ali
Adeeb Al-Sheikh
AA
Thompson
Alison
A
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D011353:Prodigiosin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; C519516:ethyl 5-((3-methoxy-5-(1H-pyrrol-2-yl)-1H-pyrrol-2-yl)methylene)-2,4-dimethyl-5H-pyrrole-3-carboxylate; D011353:Prodigiosin