STRUCTURE-FUNCTION ANALYSIS OF ANTIMICROTUBULE DINITROANILINES AGAINST PROMASTIGOTES OF THE PARASITIC PROTOZOAN LEISHMANIA-MEXICANA

Although leishmaniasis is a Major tropical disease, the currently avai lable drugs are toxic and inadequate. We show that the antimicrotubule herbicide trifluralin has antileishmania activity. The present study aimed at deducing the relationship between the structure of the molecu le and its antiprotozoan activity. Nine dinitroanilines, all of which were analogs of trifluralin, were compared. We found that pendimethali n was 2.5-fold more potent than trifluralin, and the higher efficacy m ay be correlated with molecular structural features that increase the accessibility to one nitro group. This association was further support ed by molecular modeling. Moreover, trifluralin samples from two sourc es differed in their activities by more than threefold, and gas column chromatography showed that impurities were present in the more potent sample.