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Abstract Title:

Inhibition ofβ-amyloid-induced neurotoxicity by planar analogues of procyanidin B3.

Abstract Source:

Bioorg Med Chem Lett. 2019 Jul 23. Epub 2019 Jul 23. PMID: 31371134

Abstract Author(s):

Mirei Mizuno, Kazunori Mori, Takashi Misawa, Takashi Takaki, Yosuke Demizu, Motoko Shibanuma, Kiyoshi Fukuhara

Article Affiliation:

Mirei Mizuno

Abstract:

Reactive oxygen species (ROS) are known to be produced during the amyloid beta (Aβ) aggregation process. Both ROS production and Aβ fibril formation can result in nerve cell injury. Proanthocyanidins are oligomers of catechin that can act as inhibitors of Aβ aggregation. Procyanidin B3 (Cat-Cat), the dimer of (+)-catechin, can easily cross the blood-brain barrier. Previously,we synthesized two derivatives of Cat-Cat, namely Cat-PCat and PCat-PCat, in which the geometry of one or both catechin molecules in Cat-Cat was constrained to be planar. The antioxidative activities of Cat-PCat and PCat-PCat were found to be stronger than that of Cat-Cat, with PCat-PC at exhibiting the most potent activity. These compounds are predicted to protect against Aβ-induced neurotoxicity via inhibition of Aβ aggregation as well as by antioxidative effects toward Aβ-induced intracellular ROS generation. PCat-PCat exhibited the most potent neuroprotective effects against Aβ-induced cytotoxicity, which resulted from inhibition of β-sheet structure formation during the Aβ aggregation process. PCat-PCat may be a promising lead compound for the treatment of Alzheimer's disease.

Study Type : In Vitro Study

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