Herbicides to curb human parasitic infections: in vitro and in vivo effects of trifluralin on the trypanosomatid protozoans.
Leishmaniasis is a major tropical disease for which current chemotherapies, pentavalent antimonials, are inadequate and cause severe side effects. It has been reported that trifluralin, a microtubule-disrupting herbicide, is inhibitory to Leishmania amazonensis. In this study, the in vitro effect of trifluralin on different species of trypanosomatid protozoans was determined. In addition to L. amazonensis, trifluralin is effective against Leishmania major and Leishmania tropica, which cause cutaneous infections, Leishmania donovani, which causes visceral disease, Leishmania panamensis, which may cause mucocutaneous infection, and Trypanosoma brucei, an important human and veterinary pathogen. Moreover, most encouragingly, trifluralin is effective in vivo as a topical ointment against L. major and Leishmania mexicana murine cutaneous leishmaniasis. Thus, trifluralin is a promising lead drug for several related, prevalent tropical diseases: leishmaniasis, trypanosomiasis of animals, and, possibly, African trypanosomiasis in humans.
Department of Biological Sciences, Rutgers, State University of New Jersey, Piscataway 08855-1059.
M M
MM
Chan
M
M
Grogl
C C
CC
Chen
E J
EJ
Bienen
D
D
Fong
D000818:Animals; D000890:Anti-Infective Agents / Q000633:toxicity*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006540:Herbicides; D006801:Humans; D007891:Leishmania / Q000187:drug effects* / Q000502:physiology; D007893:Leishmania donovani / Q000187:drug effects / Q000502:physiology; D007894:Leishmania mexicana / Q000187:drug effects / Q000502:physiology; D007896:Leishmaniasis / Q000188:drug therapy / Q000517:prevention & control*; D008264:Macrophages; D051379:Mice; D008807:Mice, Inbred BALB C; D014274:Trifluralin / Q000627:therapeutic use / Q000633:toxicity*; D014344:Trypanocidal Agents / Q000633:toxicity*; D014346:Trypanosoma brucei brucei / Q000187:drug effects* / Q000502:physiology; D014352:Trypanosomiasis / Q000517:prevention & control*
D000890:Anti-Infective Agents; D006540:Herbicides; D014344:Trypanocidal Agents; D014274:Trifluralin