Synthesis and Evaluation of Novel 2,2-Dimethylthiochromanones as Anti-Leishmanial Agents

Within this work, we describe the design and synthesis of a range of novel thiochromanones based on natural products reported to possess anti-leishmanial action, and their synthetic derivatives. All compounds were elaborated via the key intermediate 2,2,6-trimethoxythiochromanone, which was modified at the benzylic position to afford various ester, amine and amide analogues, substituted by chains of varying lipophilicity. Upon testing in Leishmania, IC₅₀ values revealed the most potent compounds to be phenylalkenyl and haloalkyl amides 11a and 11e, with IC₅₀ values of 10.5 and 7.2 μM, respectively.