Journal
BIOORGANIC CHEMISTRY
Volume 80, Issue -, Pages 498-510Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bioorg.2018.04.012
Keywords
2,1-Benzothiazine; 2,2-Dioxides; Hydrazones; Monoamine oxidases; Molecular dynamic simulations; Docking studies
Funding
- Higher Education Commission of Pakistan [20-3715/NRPU/RD/HEC/14/162, 20-3733/NRPU/RD/14/520]
- Government College University, Faisalabad, Pakistan
- Universiti Teknologi MARA [UiTM 600- IRMI/FRGS 5/3 (0119/2016), 600-RMI/DANA5/3 LESTARI (92/2015)]
- Organization for the Prohibition of Chemical Weapons (OPCW), The Hague, The Netherlands [20-3733/NRPU/RD/14/520]
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In this research work, we report the synthesis and biological evaluation of two new series of 1-benzyl-4-(benzylidenehydrazono)-3,4-dihydro-1H-benzo[c] [1,2]thiazine 2,2-dioxides and 1-benzyl-4((1-phenylethylidene) hydrazono)-3,4-dihydro-1H-benzo [c] [1,2]thiazine 2,2-dioxides. The synthetic plan involves the mesylation of methyl anthranilate with subsequent N-benzylation of the product. The methyl 2-(N-benzylmethylsulfonamido) benzoate was subjected to cyclization reaction in the presence of sodium hydride to obtain 1-benzyl-1H-benzo[c] [1,2]thiazin-4(3H)-one 2,2-dioxide which was treated with hydrazine hydrate to get corresponding hydrazone precursor. Finally, the titled compounds were obtained by reaction of hydrazone with various substituted aldehydes and ketones. The synthesized derivatives were subjected to carry out their inhibition activities against monoamine oxidases along with modelling investigations to evaluate their binding interactions and dynamic stability during the docking studies. The inhibition profile of potent compounds was found as competitive for both the isozymes. The compounds were more selective inhibitors of MAO-A as compared to MAO-B. Moreover, drug likeness profile of the derivatives was evaluated to have an additional insight into the physicochemical properties. The molecular dynamic simulations predicted the behaviour of amino acids with the active site residues.
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