title: Syntheses and evaluation of novel isoliquiritigenin derivatives as potential dual inhibitors for amyloid-beta aggregation and 5-lipoxygenase.
abstract: A series of new isoliquiritigenin (ISL) derivatives were synthesized and evaluated as dual inhibitors for amyloid-beta (Aβ) aggregation and 5-lipoxygenase (5-LO). It was found that all these synthetic compounds inhibited Aβ (1-42) aggregation effectively with their IC₅₀ values ranged from 2.2 ± 1.5 μM to 23.8 ± 2.0 μM. These derivatives also showed inhibitory activity to 5-LO with their IC50 values ranged from 6.1 ± 0.1 μM to 35.9 ± 0.3 μM. Their structure-activity relationships (SAR) and mechanisms of inhibitions were studied. This study provided potentially important information for further development of ISL derivatives as multifunctional agents for Alzheimer's disease (AD) treatment.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, People's Republic of China.
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Chen
authors.forename: Zi-Ying
authors.initials: ZY
authors.lastname: Zhang
authors.forename: Yan-Ping
authors.initials: YP
authors.lastname: Li
authors.forename: Ding
authors.initials: D
authors.lastname: Li
authors.forename: Shi-Liang
authors.initials: SL
authors.lastname: Huang
authors.forename: Lian-Quan
authors.initials: LQ
authors.lastname: Gu
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.forename: Zhi-Shu
authors.initials: ZS
authors.lastname: Huang
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001094:Arachidonate 5-Lipoxygenase / Q000737:chemistry / Q000378:metabolism*; D045744:Cell Line, Tumor; D047188:Chalcones / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic; D006801:Humans; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D062105:Molecular Docking Simulation; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism*; D055503:Protein Multimerization / Q000187:drug effects*; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship
chemical_list: D016229:Amyloid beta-Peptides; D000970:Antineoplastic Agents; D000975:Antioxidants; D047188:Chalcones; D016859:Lipoxygenase Inhibitors; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C040920:isoliquiritigenin; D001094:Arachidonate 5-Lipoxygenase
keywords: 1-ethyl-3-(3-dimethylaminoprpyl) carbodiide; 5-LO; 5-Lipoxygenase; 5-lipoxygenase; 5-lipoxygenase activating protein; AD; ADAM10; APP; Alzheimer's disease; Amyloid-beta aggregation; Anti-Alzheimer agent; Aβ; BACE1; CD; CNS; CREB; EDC; EM; FLAP; HOBt; ISL; Inhibitors; Isoliquiritigenin derivatives; MTT; N-hydroxybenzotriazole; NDGA; Resv; SAR; a disintegrin and metalloproteinase domain-containing protein 10; amyloid beta protein; amyloid precursor protein; beta-site APP cleaving enzyme 1; cAMP-response element binding protein; central nervous system; circular dichroism; electron microscopy; isoliquiritigenin; methyl thiazolyl tetrazolium; nordihydro-guaiaretic acid; resveratrol; structure–activity relationships