title: Design, synthesis, and examination of neuron protective properties of alkenylated and amidated dehydro-silybin derivatives.
abstract: A series of C7-O- and C20-O-amidated 2,3-dehydrosilybin (DHS) derivatives ((+/-)-1a-f and (+/-)-2), as well as a set of alkenylated DHS analogues ((+/-)-4a-f), were designed and de novo synthesized. A diesteric derivative of DHS ((+/-)-3) and two C23 esterified DHS analogues ((+/-)-5a and (+/-)-5b) were also prepared for comparison. The cell viability of PC12 cells, Fe(2+) chelation, lipid peroxidation (LPO), free radical scavenging, and xanthine oxidase inhibition models were utilized to evaluate their antioxidative and neuron protective properties. The study revealed that the diether at C7-OH and C20-OH as well as the monoether at C7-OH, which possess aliphatic substituted acetamides, demonstrated more potent LPO inhibition and Fe(2+) chelation compared to DHS and quercetin. Conversely, the diallyl ether at C7-OH and C20-OH was more potent in protection of PC12 cells against H(2)O(2)-induced injury than DHS and quercetin. Overall, the more lipophilic alkenylated DHS analogues were better performing neuroprotective agents than the acetamidated derivatives. The results in this study would be beneficial for optimizing the therapeutic potential of lignoflavonoids, especially in neurodegenerative disorders such as Alzheimer's and Parkinson's disease.
authors: Key Laboratory of Southern Zhejiang TCM R&D, Pharmacy School of Wenzhou Medical College, Wenzhou 325035, China.
authors: Lei Xiang
authors: LX
authors: Yang
authors: Ke Xin
authors: KX
authors: Huang
authors: Hai Bo
authors: HB
authors: Li
authors: Jing Xu
authors: JX
authors: Gong
authors: Feng
authors: F
authors: Wang
authors: Yu Bing
authors: YB
authors: Feng
authors: Qiao Feng
authors: QF
authors: Tao
authors: Yi Hang
authors: YH
authors: Wu
authors: Xiao Kun
authors: XK
authors: Li
authors: Xiu Mei
authors: XM
authors: Wu
authors: Su
authors: S
authors: Zeng
authors: Shawn
authors: S
authors: Spencer
authors: Yu
authors: Y
authors: Zhao
authors: Jia
authors: J
authors: Qu
mesh_terms: D000475:Alkenes / Q000737:chemistry*; D000544:Alzheimer Disease / Q000188:drug therapy; D000577:Amides / Q000737:chemistry*; D000818:Animals; D015195:Drug Design; D016166:Free Radical Scavengers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007502:Iron Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008958:Models, Molecular; D008968:Molecular Conformation; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D016716:PC12 Cells; D010300:Parkinson Disease / Q000188:drug therapy; D051381:Rats; D012838:Silymarin / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D013329:Structure-Activity Relationship; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
chemical_list: D000475:Alkenes; D000577:Amides; D016166:Free Radical Scavengers; D007502:Iron Chelating Agents; D018696:Neuroprotective Agents; D012838:Silymarin; C515097:dehydrosilybin; D014969:Xanthine Oxidase