In this communication we report a serendipitously discovered hybrid molecule 1, combining fragment of 3 (an in vivo active antileishmanial molecule) with H₂S donor moiety (known for bimodal behavior of cytoprotection and apoptosis), as antileishmanial agent. Compound 1 suppresses 99.82% parasitemia of L. donovani infected macrophages at 12.5 μg/ml without even deforming them (CC₅₀ > 100 μg/ml). This compound appears cytotoxic for intracellular amastigotes while cytoprotective to host macrophages. The concept can be utilized to develop high therapeutic index NCE (New Chemical Entities) for other macrophage mediated diseases like tuberculosis and cancer.

在本交流中，我们报告了一个偶然发现的杂合分子1，将3的片段（一种体内活性的抗衰老分子）与作为抗衰老剂的H ₂ S供体部分（以细胞保护和凋亡的双峰行为而著称）结合在一起。化合物1以12.5μg/ ml的浓度抑制了多巴尼酵母感染的巨噬细胞的99.82％寄生虫，甚至不会使其变形（CC ₅₀  > 100μg/ ml）。该化合物对胞内变形虫具有细胞毒性，同时对宿主巨噬细胞具有细胞保护作用。该概念可用于开发针对其他巨噬细胞介导的疾病（如结核病和癌症）的高治疗指数NCE（新化学实体）。