Antiparasitic activity of a triphenyl tin complex against Leishmania donovani.
Visceral leishmaniasis is a life-threatening human disease commonly known as kala-azar. Leishmania donovani is the causative agent of this parasitic disease transmitted by the sand fly vector to infect hosts. Triphenyl tin salicylanilide thiosemicarbazone [Ph(3)Sn(OSal.TSCZH)] (TTST) which is an organometallic complex of triphenyl tin has been evaluated to explore possibility to develop a potent chemotherapeutic agent against visceral leishmaniasis. Effect of triphenyl tin complex on growth inhibition and host--parasite interaction were examined both in vitro and in vivo. Release of toxic superoxide radical was measured spectrophotometrically through the formation of blue formazan derived from reduced nitrobluetetrazolium. To understand mode of action of Ph(3)Sn(OSal.TSCZH), superoxide dismutase activity was determined spectrophotometrically by measuring ability of this enzyme to inhibit pyrogallol autoxidation and also by activity staining of the non-denaturing polyacrylamide gels after separating superoxide dismutase. Antileishmanial activity of triphenyl tin complex were found to be effective both in vitro and in vivo at lower concentrations compared to the existing toxic drugs available. IC(50) of Ph(3)Sn(OSal.TSCZH) was calculated as 0.05+/-0.01mg/L. Intracellular survival of the parasite in host macrophages was inhibited by TTST in a dose dependent manner. Parasite burden in spleen was reduced to 87% under TTST treatment (10mg/kg body weight) and under sodium antimony gluconate (20mg/kg body weight) reduced nearly to 65%. Its action as a chemotherapeutic agent is found to be mediated through inhibition of superoxide dismutase and simultaneous release of toxic superoxide radical. We propose that Ph(3) Sn(OSal.TSCZH) may be considered as a prospective candidate to establish a better line of therapeutic process against experimental visceral leishmaniasis.
Raychaudhury
Bikramjit
B
Department of Biological Chemistry, Infectious Diseases Group, Indian Institute of Chemical Biology, 4 Raja SC Mullick Road, Kolkata 700032, India.
Banerjee
Shouvik
S
Gupta
Shreedhara
S
Singh
Ran Vir
RV
Datta
Salil C
SC
D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006224:Cricetinae; D006790:Host-Parasite Interactions; D006801:Humans; D007893:Leishmania donovani / Q000187:drug effects* / Q000254:growth & development; D007898:Leishmaniasis, Visceral / Q000188:drug therapy* / Q000469:parasitology; D017737:Macrophages, Peritoneal / Q000469:parasitology; D008647:Mesocricetus; D009947:Organotin Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D021261:Parasitic Sensitivity Tests; D013154:Spleen / Q000469:parasitology; D013482:Superoxide Dismutase / Q000378:metabolism
D000981:Antiprotozoal Agents; D009947:Organotin Compounds; D013482:Superoxide Dismutase