Antineoplastic agents. 465. Structural modification of resveratrol: sodium resverastatin phosphate.
As an extension of structure/activity investigations of resveratrol (1), phenstatin (2c), and the cancer antiangiogenesis drug sodium combretastatin A-4 phosphate (2b), syntheses of certain related stilbenes (14) and benzophenones (16) were undertaken. The trimethyl ether derivative of (Z)-resveratrol (4a) exhibited the strongest activity (GI(50) = 0.01-0.001 microg/mL) against a minipanel of human cancer cell lines. A monodemethylated derivative (14c) was converted to prodrug 14n (sodium resverastatin phosphate) for further biological evaluation. The antitubulin and antimicrobial activities of selected compounds were also evaluated.
Pettit
George R
GR
Department of Chemistry and Biochemistry, Cancer Research Institute, Arizona State University, P.O. Box 872404, Tempe, AZ 85287-2404, USA. bpettit@asu.edu
Grealish
Matthew P
MP
Jung
M Katherine
MK
Hamel
Ernest
E
Pettit
Robin K
RK
Chapuis
J-Charles
JC
Schmidt
Jean M
JM
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D001704:Biopolymers; D002455:Cell Division / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005658:Fungi / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D010755:Organophosphates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000077185:Resveratrol; D013237:Stereoisomerism; D013267:Stilbenes / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000737:chemistry; D014407:Tumor Cells, Cultured
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D001704:Biopolymers; D010755:Organophosphates; D011355:Prodrugs; D013267:Stilbenes; D014404:Tubulin; C458041:resverstatin phosphate; D000077185:Resveratrol