Dicarba-closo-dodecaboranes as a pharmacophore. Novel potent retinoidal agonists.
The synthesis and biological evaluation of the dicarba-closo-dodecaborane (carborane) derivatives of retinoids are described. Retinoidal activity was examined in terms of the differentiation-inducing ability toward human promyelocytic leukemia HL-60 cells. High retinoidal activity (agonist or antagonist for the retinoid receptor RAR) requires a carboxylic acid moiety and an appropriate hydrophobic group located at a suitable position on the molecule. 4-[4-(1,2-Dicarba-closo-dodecaboran-1-yl)phenylamino]b enzoic acids and 4-[3-(1,2-dicarba-closo-dodecaboran-1-yl)phenylamino]b enzoic acids showed potent agonistic activity at concentrations of 10(-8)-10(-9) M. The results indicate that carboranes are applicable as the hydrophobic moiety of biologically active molecules.
D001896:Boron Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D018922:HL-60 Cells / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D018168:Receptors, Retinoic Acid / Q000819:agonists*; D012176:Retinoids / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship