title: Multitarget-directed benzylideneindanone derivatives: anti-β-amyloid (Aβ) aggregation, antioxidant, metal chelation, and monoamine oxidase B (MAO-B) inhibition properties against Alzheimer's disease.
abstract: A novel series of benzylideneindanone derivatives were designed, synthesized, and evaluated as multitarget-directed ligands against Alzheimer's disease. The in vitro studies showed that most of the molecules exhibited a significant ability to inhibit self-induced β-amyloid (Aβ(1-42)) aggregation (10.5-80.1%, 20 μM) and MAO-B activity (IC(50) of 7.5-40.5 μM), to act as potential antioxidants (ORAC-FL value of 2.75-9.37), and to function as metal chelators. In particular, compound 41 had the greatest ability to inhibit Aβ(1-42) aggregation (80.1%), and MAO-B (IC(50) = 7.5 μM) was also an excellent antioxidant and metal chelator. Moreover, it is capable of inhibiting Cu(II)-induced Aβ(1-42) aggregation and disassembling the well-structured Aβ fibrils. These results indicated that compound 41 is an excellent multifunctional agent for the treatment of AD.
authors.affiliation: Institute of Drug Synthesis and Pharmaceutical Processing, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Huang
authors.forename: Chuanjun
authors.initials: C
authors.lastname: Lu
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.forename: Fei
authors.initials: F
authors.lastname: Mao
authors.forename: Zonghua
authors.initials: Z
authors.lastname: Luo
authors.forename: Tao
authors.initials: T
authors.lastname: Su
authors.forename: Huailei
authors.initials: H
authors.lastname: Jiang
authors.forename: Wenjun
authors.initials: W
authors.lastname: Shan
authors.forename: Xingshu
authors.initials: X
authors.lastname: Li
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D000682:Amyloid / Q000737:chemistry; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D000975:Antioxidants / Q000138:chemical synthesis* / Q000737:chemistry; D001597:Benzylidene Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D002413:Cations, Divalent; D002614:Chelating Agents / Q000138:chemical synthesis* / Q000737:chemistry; D003300:Copper / Q000737:chemistry; D006801:Humans; D007189:Indans / Q000138:chemical synthesis* / Q000737:chemistry; D007501:Iron / Q000737:chemistry; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000737:chemistry; D062105:Molecular Docking Simulation; D008995:Monoamine Oxidase / Q000737:chemistry / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D010446:Peptide Fragments / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry; D013329:Structure-Activity Relationship; D015032:Zinc / Q000737:chemistry
chemical_list: C577118:5,6-dihydroxy-2-(4-(methyl(propyl)amino)benzylidene)-2,3-dihydro-1H-inden-1-one; D000682:Amyloid; D016229:Amyloid beta-Peptides; D000975:Antioxidants; D001597:Benzylidene Compounds; D002413:Cations, Divalent; D002614:Chelating Agents; D007189:Indans; D007527:Isoenzymes; D008996:Monoamine Oxidase Inhibitors; D010446:Peptide Fragments; D011994:Recombinant Proteins; C075222:amyloid beta-protein (1-42); D003300:Copper; D007501:Iron; D008995:Monoamine Oxidase; D015032:Zinc