**In vitro** and **in vivo** prophylactic and curative activity of the triterpene saponin PX-6518 against cutaneous **Leishmania** species
Inocêncio da Luz, Raquel Andreia
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences. Pharmacy
The journal of antimicrobial chemotherapy. - London, 1975, currens
, p. 350-353
University of Antwerp
Objectives The oleanane triterpene saponin PX-6518, with known potent in vitro and in vivo activity against Leishmania donovani, was investigated for its spectrum against the cutaneous species Leishmania mexicana, Leishmania panamensis and Leishmania major. Methods In vitro activity was based on the reduction of amastigotes in primary peritoneal mouse macrophages. BALB/c mice were injected with 2 × 106 amastigotes in the base of the tail (L. panamensis and L. major) or the foot (L. mexicana) and subcutaneously treated with PX-6518 [110 mg/kg body weight (BW)] or Pentostam® (250 mg/kg BW SbV eq). Evolution of skin lesions was monitored in a prophylactic dose-finding study, and early curative [6 weeks post-infection (pi)] and late curative (>810 weeks pi) studies. Results While moderate susceptibility to PX-6518 was obtained in vitro (IC50: 14 µg/mL), excellent in vivo activity was demonstrated. In the prophylactic study (six administrations on alternate days, starting at 1day pi), PX-6518 was 100% effective at 1 mg/kg BW against L. mexicana and L. panamensis, whereas L. major lesions could be prevented at 2 mg/kg BW. In the early curative (1 mg/kg BW once a week for 4 weeks) and late curative (1 mg/kg BW twice a week for 4 weeks) studies, PX-6518 completely healed L. mexicana and L. panamensis lesions, whereas L. major lesions were reduced by ∼50%. Conclusions This study demonstrates that PX-6518 possesses potent and broad-spectrum prophylactic and curative efficacy against cutaneous leishmaniasis in the BALB/c mouse model. L. major was the least susceptible species tested and parasitological cure could not be obtained.