Novel A-ring and B-ring modified combretastatin A-4 (CA-4) analogues endowed with interesting cytotoxic activity.
A novel class of combretastatins, modified at A-ring or both A- and B-rings, mainly by replacement with benzofuran or benzo[b]thiophene, were synthesized. The new heterocombretastatins showed good cytotoxic activity on BMEC and H-460 cell lines. The aminocombretastatin 9f potently inhibits cell growth of BMEC and combretastatin-resistant HT-29 cell lines, with potential interest to treat colon carcinoma. Heterocombretastatins 9a,b inhibit tubulin polymerization similarly to CA-4 by having a binding to colchicine site five times stronger.
Simoni
Daniele
D
Dipartimento di Scienze Farmaceutiche, Università di Ferrara, Ferrara, Italy. smd@unife.it
Romagnoli
Romeo
R
Baruchello
Riccardo
R
Rondanin
Riccardo
R
Grisolia
Giuseppina
G
Eleopra
Marco
M
Rizzi
Michele
M
Tolomeo
Manlio
M
Giannini
Giuseppe
G
Alloatti
Domenico
D
Castorina
Massimo
M
Marcellini
Marcella
M
Pisano
Claudio
C
D000818:Animals; D001665:Binding Sites; D002417:Cattle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D042783:Endothelial Cells / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D013237:Stereoisomerism; D013267:Stilbenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000187:drug effects / Q000378:metabolism
D013267:Stilbenes; D014404:Tubulin; C529077:cis-3,4',5-trimethoxy-3'-aminostilbene; C058728:fosbretabulin