Antitumor agents, 154. Cytotoxic and antimitotic flavonols from Polanisia dodecandra.
Three flavonols, 5,3'-dihydroxy-3,6,7,8,4'-pentamethoxyflavone [1], 5,4'-dihydroxy-3,6,7,8,3'-pentamethoxyflavone [2], and quercetin 3-O-beta-D-glucopyranosyl-7-O-alpha-L-rhamnopyranoside [3], were isolated from Polanisia dodecandra. Compound 1 showed remarkable cytotoxicity in vitro against panels of central nervous system cancer (SF-268, SF-539, SNB-75, U-251), non-small cell lung cancer (HOP-62, NCI-H266, NCI-H460, NCI-H522), small cell lung cancer (DMS-114), ovarian cancer (OVCAR-3, SK-OV-3), colon cancer (HCT-116), renal cancer (UO-31), a melanoma cell line (SK-MEL-5), and two leukemia cell lines (HL-60 [TB], SR), with GI50 values in the low micromolar to nanomolar concentration range. This substance also inhibited rubulin polymerization (IC50 = 0.83 +/- 0.2 microM) and the binding of radiolabeled colchicine to tubulin with 59% inhibition when present in equimolar concentrations with colchicine. Compound 2 also showed cytotoxicity against medulloblastoma (TE-671) tumor cells with an ED50 value of 0.98 microgram/ml. Compound 1 appears to be the first example of a flavonol to exhibit potent inhibition of tubulin polymerization and, therefore, warrants further investigation as an antimitotic agent.
Shi
Q
Q
Natural Products Laboratory, School of Pharmacy, University of North Carolina, Chapel Hill 27599, USA.
Chen
K
K
Li
L
L
Chang
J J
JJ
Autry
C
C
Kozuka
M
M
Konoshima
T
T
Estes
J R
JR
Lin
C M
CM
Hamel
E
E
D000970:Antineoplastic Agents / Q000302:isolation & purification* / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification* / Q000494:pharmacology; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D005419:Flavonoids / Q000302:isolation & purification* / Q000494:pharmacology; D006801:Humans; D007624:KB Cells; D009682:Magnetic Resonance Spectroscopy; D014404:Tubulin / Q000378:metabolism; D014407:Tumor Cells, Cultured
C094782:5,3'-dihydroxy-3,6,7,8,4'-pentamethoxyflavone; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D005419:Flavonoids; D014404:Tubulin; C094781:5,4'-dihydroxy-3,6,7,8,3'-pentamethoxyflavone