Biological activity evaluation of novel monoamine oxidase inhibitory compounds targeting Parkinson disease

• Published in: Future medicinal chemistry 2022-11, Vol.14 (22), p.1663-1679
• Main Authors: Dawbaa, Sam, Evren, Asaf Evrim, Sağlik, Begüm Nurpelin, Gundogdu-Karaburun, Nalan, Karaburun, Ahmet Cagri
• Format: Article
• Language: English
• Subjects: benzofuran; carbohydrazide; Humans; Mass Spectrometry; molecular docking; Molecular Docking Simulation; molecular dynamics simulation; Molecular Structure; Monoamine Oxidase - metabolism; monoamine oxidase inhibitors; Monoamine Oxidase Inhibitors - chemistry; Monoamine Oxidase Inhibitors - pharmacology; oxadiazol; Parkinson disease; Parkinson Disease - drug therapy; Structure-Activity Relationship
• ISSN: 1756-8919; 1756-8927
• DOI: 10.4155/fmc-2022-0167

Design of 5-methoxy benzofuran hybrids with 2-carbohydrazide and 2-(1,3,4-oxadiazol-2-yl) as potential inhibitors of monoamine oxidase (MAO)-B targeting Parkinson disease. 12 compounds were synthesized and analyzed via high-resolution mass spectrometry, H nuclear magnetic resonance and C nuclear magnetic resonance techniques. fluorometric assay was used to investigate the activity of the synthesized compounds on both MAO-A and MAO-B isozymes. Three compounds – , and – displayed half maximal inhibitory concentration values of 0.051 ± 0.002, 0.038 ± 0.001 and 0.077 ± 0.003 μM in the inhibition of MAO-A and 0.048 ± 0.002, 0.040 ± 0.001 and 0.072 ± 0.002 μM for MAO-B, respectively. A molecular dynamics simulation study showed that compound has poor stability as a complex with MAO-A. Compound may be a potential candidate for the treatment of Parkinson disease.