title: Design, synthesis and biological evaluation of imine resveratrol derivatives as multi-targeted agents against Alzheimer's disease.
abstract: A series of imine resveratrol derivatives (1-20) have been designed, synthesized, and evaluated as multi-targeted compounds for the treatment of Alzheimer's disease (AD). In vitro studies show that most of the molecules exhibit a significant ability to inhibit self-induced and Cu(2+)-induced β-amyloid (Aβ₁₋₄₂) aggregation, and to function as potential antioxidants and biometal chelators. In particular, compound 9 is a potential lead compound for AD treatment (for compound 9, IC₅₀ = 14.1 μM for the antioxidant activity using DPPH free radical method; 64.6% at 20 μM for self-induced Aβ aggregation). Moreover, it is capable of decreasing reactive oxygen species (ROS) induced by Cu-Aβ and shows good neuroprotective effects in human SH-SY5Y neuroblastoma cells. Taken together, these results suggest that 9 might be a promising lead compound for AD treatment.
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, People's Republic of China.
authors.forename: Su-Yi
authors.initials: SY
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, People's Republic of China.
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, People's Republic of China. Electronic address: cpu_lykong@126.com.
authors.forename: Ling-Yi
authors.initials: LY
authors.lastname: Kong
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000378:metabolism; D000975:Antioxidants / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003300:Copper / Q000378:metabolism; D006801:Humans; D018696:Neuroprotective Agents / Q000737:chemistry* / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D013267:Stilbenes; D003300:Copper; D000077185:Resveratrol
keywords: Alzheimer's disease; Antioxidant; BSVVLXIGPDFSEZ-RIYZIHGNSA-N; CHBGIQHEGBKNGA-NTEUORMPSA-N; COFLOZFCNFCJFM-OQLLNIDSSA-N; CPOKOAWVSUHOCZ-MHWRWJLKSA-N; CXQBWMKQSJPURB-XNTDXEJSSA-N; DTKVTDFIUFYZDW-OQLLNIDSSA-N; GJZBNSJPZKCNPU-LFIBNONCSA-N; GRWIZXASAOKOEZ-GXDHUFHOSA-N; IUPUQXNVHRUSEI-OQLLNIDSSA-N; IWCJTSCDZDXKBK-OQLLNIDSSA-N; KILNMRJUXROOCU-NTEUORMPSA-N; Metal chelator; Neuroprotection; OZUBFLPYRPJKQL-XNTDXEJSSA-N; POLJRSQMPKDDIY-NTEUORMPSA-N; PQKMAPANQMNEHB-NTEUORMPSA-N; QIYHCQVVYSSDTI-GXDHUFHOSA-N; Resveratrol derivatives; SDHKTTFTBJGDQX-OQLLNIDSSA-N; UALRWOGQNILXLJ-NTEUORMPSA-N; USHSXCMBQPJHEF-OQLLNIDSSA-N; VISLUSLXCVLVTQ-RIYZIHGNSA-N; ZUHWLAWLODQICJ-OQLLNIDSSA-N; β-Amyloid aggregation