Alzheimer's disease is
neurodegenerative disorder due to the accumulation of
amyloid- β in the brain and causes
dementia with ageing. Some researches indicate that the RXR agonist,
Targretin, has also been used for treatment of
Alzheimer's disease in mouse models. We investigate the potent candidates as RXR agonists from the vast repertoire of TCM compounds in TCM Database@Taiwan. The potential TCM compounds, β -
lipoic acid and sulfanilic
acid, had higher potent binding affinities than both
9-cis-retinoic acid and
Targretin in docking simulation and have stable H-bonds with residues Arg316 and some equivalent hydrophobic contacts with residues Ala272, Gln275, Leu309, Phe313, Val342, Ile345, and Cys432 as
Targretin. The carboxyl or sulfonyl
hydroxide group can form a H-bond with key residue Arg316 in the docking pose, and the phenyl group next to the carboxyl or sulfonyl
hydroxide group can form a π interaction with residue Phe313. Moreover, β -
lipoic acid and sulfanilic
acid have stable H-bonds with residue Gln275, Ser313, and residue Ala327, respectively, which may strengthen and stabilize TCM candidates inside the binding domain of
RXR protein. Hence, we propose β -
lipoic acid and sulfanilic
acid as potential lead compounds for further study in
drug development process with the
RXR protein against
Alzheimer's disease.