Synthesis and <i>In Vitro</i> 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.