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

Abstract

We report in this study the in vivo efficacy of nine 2-substituted quinolines on the Leishmania amazonensis cutaneous infection murine model and on the Leishmania infantum and Leishmania donovani visceral infection murine models. In the case of the L. amazonensis model, quinolines were administered orally at 25 mg/kg twice daily for 15 days. Quinolines 1, 2, 3, and 7 reduced by 80 to 90% the parasite burdens in the lesion, whereas N-methylglucamine antimoniate (Glucantime), administered by subcutaneous injections at 100 mg [28 mg Sb(V)] per kg of body weight daily, reduced the parasite burdens by 98%. In visceral leishmaniasis due to L. infantum, mice treated orally at 25 mg/kg daily for 10 days with quinolines 1, 4, 5, and 6 showed a significant reduction of parasite burdens in the liver and spleen. These quinolines were significantly more effective than meglumine antimoniate to reduce the parasite burden in both the liver and spleen. Also, the oral in vivo activity of three quinolines (quinolines 4, 5, and 2-n-propylquinoline) were determined against L. donovani (LV 9) at 12.5 and 25 mg/kg for 10 days. Their activity was compared with that of miltefosine at 7.5 mg/kg. Miltefosine, 2-n-propylquinoline, and quinoline 5 at 12.5 mg/kg significantly reduced the parasite burdens in the liver by 72, 66, and 61%, respectively. From the present study, quinoline 5 is the most promising compound against both cutaneous and visceral leishmaniasis. The double antileishmanial and antiviral activities of these compounds suggest that this series could be a potential treatment for coinfection of Leishmania-human immunodeficiency virus.

Thermoterapy effective and safer than miltefosine in the treatment of cutaneous leishmaniasis in Colombia

“…Miltefosine (hexadecylphosphocholine) is an oral medication initially developed as an anti-tumoral agent 28 that later showed in vitro and in vivo activity against Leishmania spp 5,6,15,28,37 . In India, where resistance to antimonial agents is very high, miltefosine has been used since 1998 for the treatment of Visceral Leishmaniasis (VL) produced by L. donovani 7,24 .…”

Discovery of Safe and Orally Effective 4-Aminoquinaldine Analogues as Apoptotic Inducers with Activity against Experimental Visceral Leishmaniasis

“…Among these, 2-, 3-, and 4-substituted quinolines were reported to exhibit activity against L. donovani in vitro (29,54). Moreover, two categories of 2-substituted quinoline derivatives were investigated for in vivo activity at a 25-mg/kg dose daily for 10 days through the oral route and demonstrated 66% and 69% reductions in liver parasite burden in the murine VL model, respectively (36). Herein, PP-10, a lead compound of the 4-aminoquinaldine series, demonstrated almost complete clearance of the parasites (97% in liver and 98.5% in spleen) from infected BALB/c mice, when treated orally at a dose of 10 mg/kg/week for 1 month.…”

Antiulcer Activity after Oral Administration of the Wormwood Ethanol Extract on Lesions due to <I>Leishmania major</I> Parasites in BALB/C Mice

“…The toxicity resulting from the oil-based formulations is also implicated, which is compatible with the data from the present study. Orally administered chemotherapeutic agents (e.g., as salt) have the privilege of minimizing socioeconomic problems associated with populations living in endemic areas where the infrastructure of health care facilities is rudimentary 30 . The leaf and seed extracts of the annual or sweet wormwood, Artemisia annua, have been shown to mediate apoptosis in Leishmania donovani, the cause of visceral leishmaniasis (Kala-azar) in the Indian subcontinent 19 .…”