title: Benzothiazole Amphiphiles Ameliorate Amyloid β-Related Cell Toxicity and Oxidative Stress.
abstract: Oxidative stress from the increase of reactive oxygen species in cells is a common part of the normal aging process and is accelerated in patients with Alzheimer's disease (AD). Herein, we report the evaluation of three benzothiazole amphiphiles (BAMs) that exhibit improved biocompatibility without loss of biological activity against amyloid-β induced cell damage compared to a previously reported hexa(ethylene glycol) derivative of benzothiazole aniline (BTA-EG6). The reduced toxicity of these BAM agents compared to BTA-EG6 corresponded with their reduced propensity to induce membrane lysis. In addition, all of the new BAMs were capable of protecting differentiated SH-SY5Y neuroblastoma cells from toxicity and concomitant oxidative stress induced by AD-related aggregated Aβ (1-42) peptides. Binding and microscopy studies support that these BAM agents target Aβ and inhibit the interactions of catalase with Aβ in cells, which, in turn, can account for an observed inhibition of Aβ-induced increases in hydrogen peroxide in cells treated with these compounds. These results support that this family of benzothiazole amphiphiles may have therapeutic potential for treating cellular damage associated with AD and other Aβ-related neurologic diseases.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego , 9500 Gilman Drive, La Jolla, California 92093-0358, United States.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Cifelli
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego , 9500 Gilman Drive, La Jolla, California 92093-0358, United States.
authors.forename: Tim S
authors.initials: TS
authors.lastname: Chung
authors.affiliation: Department of Biomedical Engineering, University of Michigan , 1101 Beal Avenue, Ann Arbor, Michigan 48109, United States.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Biomedical Engineering, University of Michigan , 1101 Beal Avenue, Ann Arbor, Michigan 48109, United States.
authors.forename: Panchika
authors.initials: P
authors.lastname: Prangkio
authors.affiliation: Department of Biomedical Engineering, University of Michigan , 1101 Beal Avenue, Ann Arbor, Michigan 48109, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Mayer
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego , 9500 Gilman Drive, La Jolla, California 92093-0358, United States.
authors.forename: Jerry
authors.initials: J
authors.lastname: Yang
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D000682:Amyloid / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000686:Amyloidosis / Q000188:drug therapy / Q000378:metabolism; D052160:Benzothiazoles / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; C005465:benzothiazole
keywords: Alzheimer’s disease (AD); Aβ; benzothiazoles; catalase; oxidative stress