Abstract |
(2E,4E,6Z,8Z)-8-(3',4'-Dihydro-1'(2H)-naphthalen-1'-ylidene)-3,7-dimethyl-2,3,6-octatrienoinic acid, 9cUAB30, is a selective rexinoid for the retinoid X nuclear receptors (RXR). 9cUAB30 displays substantial chemopreventive capacity with little toxicity and is being translated to the clinic as a novel cancer prevention agent. To improve on the potency of 9cUAB30, we synthesized 4-methyl analogs of 9cUAB30, which introduced chirality at the 4-position of the tetralone ring. The syntheses and biological evaluations of the racemic homolog and enantiomers are reported. We demonstrate that the S-enantiomer is the most potent and least toxic even though these enantiomers bind in a similar conformation in the ligand binding domain of RXR.
|
Authors | Anil Desphande, Gang Xia, LeeAnn J Boerma, Kimberly K Vines, Venkatram R Atigadda, Susan Lobo-Ruppert, Clinton J Grubbs, Fariba L Moeinpour, Craig D Smith, Konstantin Christov, Wayne J Brouillette, Donald D Muccio |
Journal | Bioorganic & medicinal chemistry
(Bioorg Med Chem)
Vol. 22
Issue 1
Pg. 178-85
(Jan 01 2014)
ISSN: 1464-3391 [Electronic] England |
PMID | 24359708
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
|
Copyright | Copyright © 2013 Elsevier Ltd. All rights reserved. |
Chemical References |
- KLF4 protein, human
- Klf4 protein, rat
- Kruppel-Like Factor 4
- Ligands
- Retinoid X Receptors
- Retinoids
|
Topics |
- Humans
- Kruppel-Like Factor 4
- Ligands
- Molecular Conformation
- Neoplasms
(prevention & control, therapy)
- Retinoid X Receptors
(metabolism)
- Retinoids
(chemistry, metabolism)
|