TY - JOUR
T1 - Synthesis and biological evaluation of novel flavonols as potential anti-prostate cancer agents
AU - Britton, Robert G.
AU - Horner-Glister, Emma
AU - Pomenya, Odette A.
AU - Smith, Ewan E.
AU - Denton, Roanne
AU - Jenkins, Paul R.
AU - Steward, William P.
AU - Brown, Karen
AU - Gescher, Andreas
AU - Sale, Stewart
N1 - Funding Information:
This work was funded by a programme grant from Cancer Research UK ( C325/A13101 ) and a grant from Prostate Action ( G2009/25 ). Thanks to Dr A. Stuart for proof reading.
PY - 2012/8
Y1 - 2012/8
N2 - 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 (IC50 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) (IC50 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.
AB - 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 (IC50 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) (IC50 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.
KW - AR signalling pathway
KW - Flavonols
KW - Prostate cancer management
UR - http://www.scopus.com/inward/record.url?scp=84864399953&partnerID=8YFLogxK
U2 - 10.1016/j.ejmech.2012.06.031
DO - 10.1016/j.ejmech.2012.06.031
M3 - Article
C2 - 22789812
AN - SCOPUS:84864399953
SN - 0223-5234
VL - 54
SP - 952
EP - 958
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
ER -