In vitro activities of position 2 substitution-bearing 6-nitro- and 6-amino-benzothiazoles and their corresponding anthranilic acid derivatives against Leishmania infantum and Trichomonas vaginalis.
6-Nitro- and 6-amino-benzothiazoles bearing different chains in position 2 and their corresponding anthranilic acid derivatives were investigated for their in vitro antiparasitic properties against parasites of the species Leishmania infantum and Trichomonas vaginalis compared to their toxicity towards human monocytes. Biological investigations established that the antiprotozoal properties depended greatly on the chemical structure of the position 2 substitution-bearing group. Compound C1, 2-[(2-chloro-benzothiazol-6-yl) amino] benzoic acid, demonstrated an interesting antiproliferative activity towards parasites of the species T. vaginalis, while compound C11, 2-([2-[(2-hydroxyethyl) amino]-benzothiazol-6-yl] amino) benzoic acid, exhibited a promising activity against parasites of the species L. infantum in their intracellular amastigote form. Additional experiments established that compound C11, which was poorly toxic against the promastigote and the extracellular amastigote forms of the parasite, could improve host-protective mechanisms against Leishmania by preventing parasite internalization by macrophages and stimulating NO production, by means of a mechanism synergistically enhanced by the presence of gamma interferon.
Delmas
Florence
F
Laboratoire de Parasitologie, Hygiène et Zoologie, Faculté de Pharmacie, Université d'Aix-Marseille II, 27 Boulevard Jean Moulin, 13385 Marseille Cedex 05, France.
Di Giorgio
Carole
C
Robin
Maxime
M
Azas
Nadine
N
Gasquet
Monique
M
Detang
Claire
C
Costa
Muriel
M
Timon-David
Pierre
P
Galy
Jean-Pierre
JP
D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D018314:Leishmania infantum / Q000187:drug effects* / Q000254:growth & development; D009000:Monocytes / Q000187:drug effects / Q000469:parasitology; D009569:Nitric Oxide / Q000378:metabolism; D009574:Nitro Compounds / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D012995:Solubility; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D014246:Trichomonas vaginalis / Q000187:drug effects* / Q000254:growth & development; D062367:ortho-Aminobenzoates / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity
D000981:Antiprotozoal Agents; D007202:Indicators and Reagents; D009574:Nitro Compounds; D013844:Thiazoles; D062367:ortho-Aminobenzoates; D009569:Nitric Oxide