Study on Experimental Leishmanicidal Activity and in silico of Cytochalasin B

Leishmaniasis is a neglected infectious disease caused by different species of the Leishmania parasite and is one of the major public health problems in developing countries. Despite the progress in fundamental knowledge about the Leishmania parasite, current therapy against leishmaniasis is still unsatisfactory due to limited efficacy, prolonged treatment, high cost and undesirable adverse effects. Thus, the research for new prototypes compounds of antileishmaniasis drugs remains a matter of current importance. The objective of this study was to evaluate the leishmanicidal activity of cytochalasin B, a natural compound isolated by our group in a previous study, against L. amazonensis, using experimental tests and computational simulation methodologies. The results of the biological evaluation showed that cytochalasin B has antileishmanial activity against the promastigote form of Leishmania amazonensis. These results are corroborated by the docking and molecular dynamics that showed that the activity occurs due to the inactivation of the trypanothione reductase enzyme (TryR).

利什曼病（Leishmaniasis）是一类由多种利什曼原虫（Leishmania parasite）引发的被忽视传染病，亦是发展中国家面临的主要公共卫生问题之一。尽管当前针对利什曼原虫的基础研究已取得一定进展，但现有抗利什曼病疗法仍存在疗效有限、疗程冗长、成本高昂且不良反应显著等缺陷，难以满足临床需求。因此，研发新型抗利什曼病药物候选化合物仍是当前的重要研究方向。本研究旨在通过实验测试与计算机模拟相结合的方法，评估本团队既往研究中分离得到的天然化合物细胞松弛素B（cytochalasin B）对亚马逊利什曼原虫（Leishmania amazonensis，缩写L. amazonensis）的杀利什曼原虫活性。生物学评估结果显示，细胞松弛素B对亚马逊利什曼原虫的前鞭毛体（promastigote）形式具有明确的抗利什曼活性。分子对接与分子动力学模拟结果进一步验证了上述结论，证实该活性的发挥机制为锥硫醇还原酶（Trypanothione Reductase，TryR）的失活。