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Publication Type : Journal Article
Publisher : Process Biochemistry
Source : Process Biochemistry, Volume 99, p.246-253 (2020)
Url : https://www.sciencedirect.com/science/article/pii/S1359511320304578
Keywords : acetylcholinesterase, Imines, kinetics, Monoamine oxidase-A, Monoamine oxidase-B, Reversibility
Campus : Kochi
School : School of Pharmacy
Department : Pharmaceutical Chemistry & Analysis
Year : 2020
Abstract : {A series of eleven 1-methyl, 5-phenyl substituted thiosemicarbazones (MT1–MT11) with the phenyl ring substitutions were prepared and investigated for their inhibitory activities against monoamine oxidases (MAOs) and acetylcholinesterase (AChE). [4-(dimethylamino) phenyl]methylidene-N-methylhydrazine-1-carbothioamide (MT5) inhibited MAO-B potently with an IC50 of 8.77 μM. Potencies for MAO-B increased in the order N(CH3)2 in MT5 > OCH3 in MT3 > Br in MT9. Most of the 11 compounds weakly inhibited AChE by <30% at 10 μM. MT5 competitively inhibited MAO-B and Ki value was 6.58 ± 0.064 μM. Reversibility experiments showed MT5 also reversibly inhibited MAO-B. MTT assays revealed that MT5 and MT3 were non-toxic to normal VERO cell lines with IC50 values of 191.96 and 187.04 μg/mL, respectively. From the molecular docking, MT5 binding was found to be stabilized by hydrogen bonding to the non-bonding electron of the terminal N-methyl group with Cys172 (binding energy = −7.01 kcal/mol) of MAO-B. The molecular dynamics further predicted that MT5 had a major π–π hydrophobic interaction with Tyr326 of MAO-B, suggesting that it plays an important role in the stabilization of protein-ligand interaction.These results documents that MT5 is a moderately selective, reversible, and competitive inhibitor of MAO-B with low cytotoxic profile.
Cite this Research Publication : G. Elizabeth Mathew, Oh, J. Min, Mohan, K., Kumudhavalli, M. V., Jayanthi, S., Kim, H., and Bijo Mathew, “Inhibitions of monoamine oxidases and acetylcholinesterase by 1-methyl, 5-phenyl substituted thiosemicarbazones: Synthesis, biochemical, and computational investigations”, Process Biochemistry, vol. 99, pp. 246-253, 2020.