Synthesis and in silico studies of Novel Ru(II) complexes of Schiff base derivatives of 3-[(4-amino-5-thioxo-1,2,4-triazole-3-yl)methyl]-2(3H)-benzoxazolone compounds as potent Glutathione S-transferase and Cholinesterases Inhibitor

Novel Ru(II) complexes of Shiff base derivatives of 3-[(4-amino-5-thioxo-1,2,4-triazole-3-yl)methyl]-2(3H)benzoxazolone were synthesized. The ligands (1a-e) were confirmed by IR, H-1 NMR, and C-13 NMR spectra (only 1b and 1c). Structures of the synthesized Ru(II) complexes (2a-e) were illuminated by elemental analysis, IR, H-1 NMR, C-13 NMR, and mass spectra. As the biological studies, the inhibitory potency of the ligands and the novel synthesized complexes were evaluated against the glutathione S-transferase (GST), acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes in vitro conditions. Ki values in the range of 26.87-47.63 mu M for AChE, 23.51-42.81 mu M for BChE, and 33.14-51.73 mu M for GST, respectively. The free binding energy of most active inhibitors against AChE, BChE, and GST enzymes were detected as-10.183 kcal/mol, -9.111 kcal/mol, and -6.097 kcal/mol, respectively. All compounds docked were observed to bind in the active site of the enzymes with similar binding orientation and binding interactions with the surrounding amino acids. (C) 2021 Published by Elsevier B.V.

Automated summary

Novel Ru(II) complexes of Shiff base derivatives were synthesized and their structures confirmed. The inhibitory potency of the complexes against various enzymes was evaluated, showing significant inhibitory activity with promising Ki values. The compounds were observed to bind in the active site of the enzymes with similar binding orientation and interactions.