Synthesis and biological evaluation of 4-chloro-3, 5-dinitrobenzotrifluoride analogues as antileishmanial agents.
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.
Pitzer
K K
KK
Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Washington, D.C., 20307-5100, USA. CPT_Kevin_Pitzer@wrsmtp-ccmail.army.mil
Werbovetz
K A
KA
Brendle
J J
JJ
Scovill
J P
JP
D000818:Animals; D006224:Cricetinae; D020128:Inhibitory Concentration 50; D007893:Leishmania donovani / Q000187:drug effects*; D007896:Leishmaniasis / Q000469:parasitology; D008099:Liver / Q000187:drug effects / Q000469:parasitology; D008647:Mesocricetus; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000096926:Benzenesulfonamides
D011759:Pyrrolidines; D013449:Sulfonamides; D014344:Trypanocidal Agents; C115934:pyrrolidyl-2-pyrrolidyl-5-(trifluoromethyl)benzenesulfonamide; D000096926:Benzenesulfonamides