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 SM5, SM4, and SM9 most inhibited MAO-B with IC₅₀ 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 SM5 had the highest selectivity index (SI) value for MAO-B (>7.30), followed by SM4 (>5.67). Kinetic experiments revealed that SM5 competitively inhibited MAO-B, with a mean K_i value of 2.39 ± 0.15 µM. Reversibility experiments showed that SM5 reversibly inhibited MAO-B, and 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assays revealed that SM5 was not toxic to Vero cells (IC₅₀ = 198.96 µg/mL). The SM5/MAO-B interaction was ascertained by molecular docking and dynamics studies. The study shows that SM5 competitively inhibits MAO-B in a reversible, moderate selective manner, and that it is non-toxic to Vero cells.

Communicated by Ramaswamy H. Sarma

选择性单胺氧化酶-B（MAO-B）抑制是治疗帕金森氏病（PD）的诱人对象。在当前的研究中，我们合成了一些选定的甲硫基半脲酮衍生物，并研究了它们的MAO和乙酰胆碱酯酶（AChE）抑制活性。在合成的系列中，化合物SM5，SM4和SM9对MAO-B的抑制最大，IC ₅₀值分别为5.48、7.06和8.03 µM。所有测试的化合物均以10 µM的浓度弱抑制MAO-A，残留活性> 50％。化合物SM5对MAO-B的选择性指数（SI）最高（> 7.30），其次是SM4（> 5.67）。动力学实验表明SM5具有竞争性抑制作用的MAO-B，平均K _i值为2.39±0.15 µM。可逆性实验表明，SM5可逆地抑制MAO-B，而3-（4,5-二甲基噻唑基-2）-2,5-二苯基四氮唑溴化物（MTT）分析表明SM5对Vero细胞无毒（IC ₅₀ = 198.96 µg /毫升）。该SM5 / MAO-B的相互作用是通过分子对接和动力学研究确定。研究表明，SM5以可逆的，中等选择性的方式竞争性抑制MAO-B，并且对Vero细胞无毒。

由Ramaswamy H.Sarma沟通