Dicarba-closo-dodecaboranes as a pharmacophore. Retinoidal antagonists and potential agonists.
Synthesis and biological evaluation of the first dicarba-closo-dodecaborane (carborane) derivatives of retinoids are described. Their retinoidal activity were examined in terms of the differentiation-inducing ability toward human promyelocytic leukemia HL-60 cells. High retinoidal activity (agonist or antagonist for retinoic acid receptor (RAR) requires a carboxylic acid moiety and an appropriate hydrophobic group located at a suitable position on the molecule. The 4-carboranyl-substituted compounds (7, 11) showed antagonistic activity but no agonistic activity even in the presence of the potent synergist HX630. On the other hand, the 3-carboranyl-substituted compounds (8, 12) showed potential agonistic activity, but no antagonistic activity. The results indicates that carboranes are applicable as the hydrophobic moiety of biologically active molecules.
Iijima
T
T
Graduate School of Pharmaceutical Sciences, University of Tokyo, Japan.
Endo
Y
Y
Tsuji
M
M
Kawachi
E
E
Kagechika
H
H
Shudo
K
K
D001896:Boron Compounds / Q000138:chemical synthesis*; D002454:Cell Differentiation / Q000187:drug effects; D006098:Granulocytes / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D018168:Receptors, Retinoic Acid / Q000819:agonists* / Q000037:antagonists & inhibitors*; D012176:Retinoids / Q000138:chemical synthesis*
D001896:Boron Compounds; D018168:Receptors, Retinoic Acid; D012176:Retinoids