Design, synthesis and biological evaluation of novel stilbene-based antitumor agents.
A series of novel stilbene derivatives has been synthesized and studied with the main goal to investigate SAR of the amino compound 1a, as well as to improve its water solubility, a potentially negative aspect of the molecule that could be a serious obstacle for a pre-clinical development. We have obtained derivatives with good cytotoxic activity, in particular, the derivatives 5c and 6b could represent two novel leads for further investigation. Compound 8b, a morpholino-carbamate derivative, prodrug of 1a, has a very good solubility in water, and is active in suppressing growth of tumor cells at a concentration of 5000 nM, which is a concentration 100 times higher than the parent stilbene 1a.
Simoni
Daniele
D
Dipartimento di Scienze Farmaceutiche, Università di Ferrara, via Fossato di Mortara 17/19, I-44100 Ferrara, Italy. smd@unife.it
Invidiata
Francesco Paolo
FP
Eleopra
Marco
M
Marchetti
Paolo
P
Rondanin
Riccardo
R
Baruchello
Riccardo
R
Grisolia
Giuseppina
G
Tripathi
Ashutosh
A
Kellogg
Glen E
GE
Durrant
David
D
Lee
Ray M
RM
D000588:Amines; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D011355:Prodrugs / Q000737:chemistry; D012995:Solubility; D013267:Stilbenes / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000378:metabolism
D000588:Amines; D000970:Antineoplastic Agents; D011355:Prodrugs; D013267:Stilbenes; D014404:Tubulin