Selective monoamine oxidase-B (MAO-B) inhibition is an attractive subject for the treatment of Parkinson's disease (PD). In the current study, we synthesized some selected derivatives of methylthiosemicarbazones and investigated their MAOs and acetylcholinesterase (AChE) inhibitory activities. Among the series synthesized, compounds , , and most inhibited MAO-B with IC values of 5.48, 7.06, and 8.03 µM, respectively. All compounds tested weakly inhibited MAO-A at 10 µM with the residual activities of >50%. Compound had the highest selectivity index (SI) value for MAO-B (>7.30), followed by (>5.67). Kinetic experiments revealed that competitively inhibited MAO-B, with a mean value of 2.39 ± 0.15 µM. Reversibility experiments showed that reversibly inhibited MAO-B, and 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assays revealed that was not toxic to Vero cells (IC = 198.96 µg/mL). The /MAO-B interaction was ascertained by molecular docking and dynamics studies. The study shows that competitively inhibits MAO-B in a reversible, moderate selective manner, and that it is non-toxic to Vero cells.Communicated by Ramaswamy H. Sarma.
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