The concise synthesis of chalcone, indanone and indenone analogues of combretastatin A4.
A series of aryl- and aroyl-substituted chalcone analogues of the tubulin binding agent combretastatin A4 (1) were prepared, using a recently introduced one-pot palladium-mediated hydrostannylation-coupling reaction sequence. These chalcones were converted to indanones by Nazarov cyclisation, followed by oxidation to give the corresponding indenones. Indenones were also prepared using a palladium-mediated formal [3+2]-cycloaddition process between ortho-halobenzaldehydes and diarylpropynones. All compounds were assessed as inhibitors of tubulin polymerisation, but only E-31 had activity similar to that of 1. However, compound E-31 did not exhibit antiproliferative activity against the MCF-7 cell line.
Kerr
Daniel J
DJ
Department of Medicinal Chemistry, Faculty of Pharmacy, Monash University, 381 Royal Pde, Parkville, Australia.
Hamel
Ernest
E
Jung
M Katherine
MK
Flynn
Bernard L
BL
D000818:Animals; D001921:Brain; D002417:Cattle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002599:Chalcone / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007189:Indans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007192:Indenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D013237:Stereoisomerism; D013267:Stilbenes / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000187:drug effects
D007189:Indans; D007192:Indenes; D013267:Stilbenes; D014404:Tubulin; D002599:Chalcone; C013352:indacrinone; C058728:fosbretabulin