title: Anti-neurotoxicity effects of oxoisoaporphine-lipoic acid hybrids.
abstract: Four oxoisoaporphine-lipoic acid hybrids were designed, synthesized, and investigated in this study. To develop the hybrids, the oxoisoaporphine fragment was used for its inhibition of cholinesterases and β-amyloid (Aβ) aggregation, while the unit of lipoic acid was used for its radical-capturing and neuroprotective effects. The hybrids exhibited moderate inhibitory effects on the activity of acetylcholinesterase (AChE), with IC50 values in the micromolar range and low toxicity in SH-SY5Y cells. Moreover, the learning and memory abilities, climbing capability, and average life expectancy of the Aβ42 transgenic Drosophila were all significantly improved by the hybrids. They also enhanced the intracephalic antioxidant activity, the metabolism, and the activity cholinesterase in the flies. More strikingly, Aβ42 aggregation in the hybrids-treated Drosophila was attenuated with effective neuroprotection. Our results indicate the potential of using these oxoisoaporphine-lipoic acid hybrids in AD treatments.
authors.affiliation: Affiliated Hospital of Guilin Medicine University, Guilin City, Guangxi, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Sciences of Guangxi Normal University, Guilin City, Guangxi, China.
authors.forename: Yuhuan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Sciences of Guangxi Normal University, Guilin City, Guangxi, China.
authors.forename: Shuming
authors.initials: S
authors.lastname: Zhong
authors.affiliation: Affiliated Hospital of Guilin Medicine University, Guilin City, Guangxi, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Affiliated Hospital of Guilin Medicine University, Guilin City, Guangxi, China. Electronic address: qhli1999@163.com.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Li
authors.affiliation: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Sciences of Guangxi Normal University, Guilin City, Guangxi, China. Electronic address: hyhth@163.com.
authors.forename: Huang
authors.initials: H
authors.lastname: Tang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D001060:Aporphines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004331:Drosophila melanogaster / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008315:Malondialdehyde / Q000378:metabolism; D018696:Neuroprotective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D066263:Protein Aggregation, Pathological / Q000378:metabolism / Q000517:prevention & control; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D013482:Superoxide Dismutase / Q000378:metabolism; D008063:Thioctic Acid / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D001060:Aporphines; D002800:Cholinesterase Inhibitors; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D011994:Recombinant Proteins; C075222:amyloid beta-protein (1-42); D008315:Malondialdehyde; D008063:Thioctic Acid; D000255:Adenosine Triphosphate; D013482:Superoxide Dismutase
keywords: Aβ42 transgenic Drosophila; Neuroprotection; Oxoisoaporphine derivatives; SH-SY5Y cell; Synthesis