The activity of 2-substituted quinoline alkaloids in BALB/c mice infected with Leishmania donovani

Abstract

Potent antileishmanial activity has recently been described in vivo when certain 2-substituted quinoline alkaloids are administered to mice with cutaneous leishmaniasis. We now report the antileishmanial activity of four 2-substituted quinoline alkaloids, namely chimanine D or 2-(1',2'-trans-epoxypropyl) quinoline (I), 2-n-propylquinoline (II), 2-styrylquinoline (III) and 2-(2'-hydroxypropyl) quinoline (IV), for experimental treatment of visceral leishmaniasis in infected BALB/c mice. Subcutaneous treatment with chimanine D for 10 days at 0.54 mmol/kg per day resulted in 86.6% parasite suppression in the liver. Oral administration of 0.54 mmol/kg of 2-n-propylquinoline once daily for 5 or 10 days to L. donovani-infected mice suppressed parasite burdens in liver by 87.8 and 99.9%, respectively. Cutaneous administration of meglumine antimonate for 10 days resulted in 97.4% parasite suppression in the liver. This study is, to our knowledge, the first to demonstrate the activity of 2-substituted quinoline alkaloids in experimental treatment of visceral leishmaniasis. Further biological and chemical studies of these products might yet prove helpful for the development of new antileishmanial drugs.

Efeito leishmanicida in vitro de Stachytarpheta cayennensis (Rich.) Vahl (Verbenaceae)

“…Dentre eles, podem ser citados os terpenóides (Yang;Liew, 1992;Camacho et al, 2000), aminoglicosteróides e aminosteróides (Kam et al, 1997), naftoquinonas (Fournet et al, 1992a;Kayser et al, 2000), chalconas (Chen et al, 1993), glicosídios iridóides (Mittal et al, 1998); fl avonóides (Araújo et al, 1998), neolignanas (Barata et al, 2000) e os alcalóides (Mahiou et al, 1994;Fournet et al, 1994;Queiroz et al, 1996;Akendengue et al, 1999).…”

Clinical and Experimental Advances in Treatment of Visceral Leishmaniasis

“…In addition to the preceding agents (tested in targeted and free form), review of the 1990-2000 literature indicates more than a dozen other agents with in vivo activity in experimentally infected animals (2,3,38,47,52,63,65,66,104,149,191). The selection of study drugs has been eclectic and largely empiric, and their broad array defies useful classification.…”

Efficacy of Orally Administered 2-Substituted Quinolines in Experimental Murine Cutaneous and Visceral Leishmaniases

“…Two quinolines (quinolines 3 and 7) were specifically active against cutaneous leishmaniasis, and two quinolines (quinolines 4 and 5) were only active against visceral leishmaniasis infection. We observed that 2-alkenylquinoline 3 (containing a pent-2-en-1-yl chain) had antileishmanial properties similar to those of prop2en-1-yl quinoline previously described and isolated from the Bolivian plant Galipea longiflora (10,11). With these new analogs, we can now confirm (i) their oral efficacy and (ii) the recent in vitro results obtained against the amastigote forms of L. amazonensis, L. infantum, and L. donovani (9).…”

“…Following this approach, we have previously reported the efficacy of 2-substituted quinolines in the experimental treatment of cutaneous and visceral leishmaniasis by oral and parenteral routes (10,11).…”