Synthesis and biological evaluation of novel flavonols as potential anti-prostate cancer agents.
A library of flavonol analogues was synthesised and evaluated as potential anticancer agents against a human prostate cancer cell line, 22rν1. Compounds 3, 8 and 11 (IC(50) 2.6, 3.3 and 4.0 μM respectively) showed potent cancer cell growth inhibition, comparable to the lead compound 3',4',5'-trimethoxyflavonol (1) (IC(50) 3.1 μM) and superior to the naturally occurring flavonols quercetin (16) and fisetin (22) (both >15 μM). Results indicate that the 3',4',5'- arrangement of either hydroxy (OH) or methoxy (OMe) residues is important for growth arrest of these cells and that the OMe analogues may be superior to their OH counterparts. Compounds 1, 3, 8 and 11 warrant further investigation as potential agents for the management of prostate cancer.
Department of Cancer Studies and Molecular Medicine, George Porter Building, University of Leicester, Leicester LE1 7RH, UK.
Robert G
RG
Britton
Emma
E
Horner-Glister
Odette A
OA
Pomenya
Ewan E
EE
Smith
Roanne
R
Denton
Paul R
PR
Jenkins
William P
WP
Steward
Karen
K
Brown
Andreas
A
Gescher
Stewart
S
Sale
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D001682:Biological Availability; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D004355:Drug Stability; D044948:Flavonols / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D011471:Prostatic Neoplasms / Q000473:pathology*
D000970:Antineoplastic Agents; D044948:Flavonols