Henning Nadine, Kannigadu Christina, Aucamp Janine, Janse van Rensburg Helena D, van der Kooy Frank, N'Da David D
Centre of Excellence for Pharmaceutical Sciences (Pharmacen), North-West University, Potchefstroom, 2520, South Africa.
Chem Biodivers. 2025 Jan;22(1):e202402059. doi: 10.1002/cbdv.202402059. Epub 2024 Oct 31.
Leishmaniasis is a vector-borne, parasitic disease affecting millions of people and animals worldwide. Current therapeutic options have proven to be ineffective in both treating the disease and preventing its spread. As a result, new drugs must be developed to effectively combat this disease. In this study, a series of 14 ethylene glycol analogues of benzothiadiazine-1,1-dioxide were synthesised to investigate their antileishmanial potential and cytotoxicity. Analogue 9, 2-(2-phenoxyethyl)-2H-benzo[e][1,2,4]thiadiazine-1,1-dioxide, was identified as the most inhibitory compound as it was observed to moderately inhibit the growth of L. major (IC 103 μM) and L. donovani (IC 153 μM) promastigotes. However, in general, the series presented with low biological activity, which may be attributed to reduced target affinity and/or undesired cell culture protein binding.
利什曼病是一种由媒介传播的寄生虫病，影响着全球数百万人和动物。目前的治疗方法已被证明在治疗该疾病和预防其传播方面均无效。因此，必须开发新药以有效对抗这种疾病。在本研究中，合成了一系列14种苯并噻二嗪-1,1-二氧化物的乙二醇类似物，以研究它们的抗利什曼原虫潜力和细胞毒性。类似物9，即2-(2-苯氧基乙基)-2H-苯并[e][1,2,4]噻二嗪-1,1-二氧化物，被确定为最具抑制作用的化合物，因为观察到它能适度抑制硕大利什曼原虫（IC 103 μM）和杜氏利什曼原虫（IC 153 μM）前鞭毛体的生长。然而，总体而言，该系列表现出较低的生物活性，这可能归因于靶标亲和力降低和/或不期望的细胞培养蛋白结合。
