Nam, Min-Ho Park, Moosung Park, Hyeri Kim, Youngjae Yoon, Seulki Sawant, Vikram Shahaji Choi, Ji Won Park, Jong-Hyun Park, Ki Duk Min, Sun-Joon Lee, C. Justin Chooaii, Hyunah 2024-01-20T01:03:31Z 2024-01-20T01:03:31Z 2021-09-05 2017-07 1948-7193 https://pubs.kist.re.kr/handle/201004/122571 To develop novel, selective, and reversible MAO-B inhibitors for safer treatment of Parkinson's disease, benzothiazole and benzoxazole derivatives with indole moiety were designed and synthesized. Most of the synthesized compounds showed inhibitory activities against MAO-B and selectivity over MAO-A. The most active compound was compound 5b, 6-fluoro-2-(1-methyl-IN-indol-5-yl)benzo[d]-thiazole with an IC50 value of 28 nM with no apparent effect on MAO-A activity at 10 mu M. Based on the reversibility assay, compound 5b turned out to be fully reversible with over 95% of recovery of enzyme activity after washout of the compound. Compound Sb showed a reasonable stability in human liver microsomes and did not affect the activities of CYP isozymes, suggesting an absence of high-risk drug-drug interaction. In an in vivo MPTP-induced animal model of Parkinson's disease, oral administration of compound 5b showed neuroprotection of nigrostriatal dopaminergic neurons as revealed by tyrosine hydroxylase staining and prevention of MPTP-induced parkinsonism as revealed by motor behavioral assay of vertical grid test. In summary, the novel, reversible, and selective MAO-B inhibitor compound 5b was synthesized and characterized. We propose compound 5b as an effective therapeutic compound for relieving parkinsonism. English AMER CHEMICAL SOC MONOAMINE-OXIDASE-B L-DOPA IN-VITRO DRUG SAFINAMIDE THERAPY METAANALYSIS DERIVATIVES RASAGILINE METABOLISM Indole-Substituted Benzothiazoles and Benzoxazoles as Selective and Reversible MAO-B Inhibitors for Treatment of Parkinson's Disease Article 10.1021/acschemneuro.7b00050 1 ACS CHEMICAL NEUROSCIENCE, v.8, no.7, pp.1519 - 1529 ACS CHEMICAL NEUROSCIENCE 8 7 1519 1529 scie scopus 000406174500013 2-s2.0-85024833338 Biochemistry & Molecular Biology Chemistry, Medicinal Neurosciences Biochemistry & Molecular Biology Pharmacology & Pharmacy Neurosciences & Neurology Article MONOAMINE-OXIDASE-B L-DOPA IN-VITRO DRUG SAFINAMIDE THERAPY METAANALYSIS DERIVATIVES RASAGILINE METABOLISM MAO-B MAO-B inhibitor Parkinson&apos s disease benzothiazole benzoxazole MPTP-induced animal model