Synthesis and In Vitro Antileishmanial Efficacy of Novel Ethylene Glycol Analogues of Benzothiadiazine‐1,1‐dioxide

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 (IC50 103 μM) and L. donovani (IC50 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.