title: 3,5-Diarylpyrazole Derivatives Obtained by Ammonolysis of the Total Flavonoids from Chrysanthemum indicum Extract Show Potential for the Treatment of Alzheimer's Disease.
abstract: Four new 3,5-diarylpyrazole analogues (1-4) were isolated from an extract of the flowers of Chrysanthemun indicum using a combination of ammonolysis of the total flavonoid extract and an Aβ aggregation inhibitory activity guided purification procedure. All four compounds (1-4) showed moderate to potent activity against Aβ aggregation with EC50 values of 4.3, 15.8, 1.3, and 2.9 μM, respectively. Moreover, compound 3 showed low cytotoxicity and significant neuroprotective activity against Aβ-induced cytotoxicity in the SH-SY5Y cell line. This report is the first to show that 3,5-diarylpyrazole analogues can inhibit Aβ aggregation and exhibit neuroprotective activity with potential for the treatment of Alzheimer's disease. Taken together, the method presented here offers an alternative approach to yield bioactive compounds.
authors.affiliation: †Research Center for Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, People's Republic of China.
authors.forename: Taizong
authors.initials: T
authors.lastname: Wu
authors.affiliation: †Research Center for Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, People's Republic of China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Jiang
authors.affiliation: †Research Center for Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, People's Republic of China.
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.affiliation: ‡Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, United States.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Morris-Natschke
authors.affiliation: †Research Center for Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Miao
authors.affiliation: †Research Center for Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, People's Republic of China.
authors.forename: Lianquan
authors.initials: L
authors.lastname: Gu
authors.affiliation: †Research Center for Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.affiliation: ‡Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, United States.|§Chinese Medicine Research and Development Center, China Medical University and Hospital, Taichung 401, Taiwan, ROC.
authors.forename: Kuo-Hsiung
authors.initials: KH
authors.lastname: Lee
authors.affiliation: †Research Center for Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, People's Republic of China.|‡Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, United States.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Gu
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D031202:Chrysanthemum / Q000737:chemistry*; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D035264:Flowers / Q000737:chemistry; D006801:Humans; D015394:Molecular Structure; D018696:Neuroprotective Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D019906:Nuclear Magnetic Resonance, Biomolecular; D011720:Pyrazoles / Q000737:chemistry / Q000302:isolation & purification*
chemical_list: D016229:Amyloid beta-Peptides; D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D018696:Neuroprotective Agents; D011720:Pyrazoles