Utility of boron clusters for drug design. Relation between estrogen receptor binding affinity and hydrophobicity of phenols bearing various types of carboranyl groups.
High binding affinity for estrogen receptor and the appearance of estrogenic activity require a phenolic ring and an appropriate hydrophobic group adjacent to the phenolic ring. A quantitative structure-activity relationship analysis based on the values of logP and the pK(a) of the phenolic group showed that the hydrophobicity of these compounds is highly correlated to the estrogen receptor alpha (ERalpha)-binding affinity. These results should be useful for application of these spherical boron clusters (dicarba-closo-dodecaboranes; carboranes) as hydrophobic pharmacophores in drug design, as well as for microscopic analysis of ER-ligand interactions.
Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan. yendo@tohoku-pharm.ac.jp
Yasuyuki
Y
Endo
Keisuke
K
Yamamoto
Hiroyuki
H
Kagechika
D001896:Boron Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D007700:Kinetics; D015394:Molecular Structure; D010636:Phenols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism*
D001896:Boron Compounds; D010636:Phenols; D011960:Receptors, Estrogen