1-[2-chloro-5-(trifluoromethyl)phenyl]sulfonylazepane and Leishmaniasis

Desnitro analogues of 4-chloro-3,5-dinitrobenzotrifluoride (chloralin) (2), an in vitro microtubule inhibitor of several Leishmania species, have been synthesized from 2-halo-5-(trifluoromethyl)benzenesulfonyl chlorides 4 and 5. The analogues exhibited moderate to excellent activity when tested against Leishmania donovani amastigotes in vitro. Two representative compounds, 7f and 8, were tested against the Khartoum strain of L. donovani in a hamster model using chloralin (2) and Glucantime (one of the current therapeutics of choice in the treatment of Leishmania) as standards, the results of which will be discussed herein.

Topics: Animals; Cricetinae; Inhibitory Concentration 50; Leishmania donovani; Leishmaniasis; Liver; Mesocricetus; Pyrrolidines; Structure-Activity Relationship; Sulfonamides; Trypanocidal Agents