Synthesis of some novel 2 substituted benzothiazole derivatives containing benzylamine moiety as monoamine oxidase inhibitory agents
Abstract In the present work, 12 new 2 (5 substituted benzothiazol 2 ylsulfanyl) N (substitutedbenzyl) N (4 substitutedphenyl) acetamide derivatives (4a l) was designed and synthesized. The structures of the synthesized compounds were clarified using Fourier transform infrared spectroscopy (FTIR) proton nuclear magnetic resonance (1H NMR) carbon 13 nuclear magnetic resonance (13C NMR) and high resolution mass spectrometry (HRMS) spectral data. Purity of synthesized compounds was checked by high performance liquid chromatography (HPLC) analyses and purity ratio was found between 96.5 99.9% The inhibitory activity of the compounds against MAO A and MAO B enzymes was evaluated by using in vitro flurometric method in which kynuramine was used as a substrate. Most of the compounds exhibited more selective inhibitory activity towards monoamine oxidase B (MAO B) than monoamine oxidase A (MAO A) Compound 4h was determined as the most potent compound against both enzyme types. The MAO B enzyme kinetic of the compound 4h was studied and nature of MAO B inhibition, caused by this compound, was investigated. The graphical analysis of steady state inhibition data indicated that compound 4h is a mixed type inhibitor. Theoretical calculation of absorption, distribution, metabolism, excretion (ADME) properties for the synthesized compounds was also carried out and observed data supported the potential of compound 4h.
Journal of enzyme inhibition and medicinal chemistry