In-vitro sensitivity of Pakistani Leishmania tropica field isolate against buparvaquone in comparison to standard anti-leishmanial drugs.
In this study, in vitro anti-leishmanial activity of buparvaquone was evaluated against promastigotes and intracellular amastigotes of Pakistani Leishmania tropica isolate KWH23 in relation to the current standard chemotherapy for leishmaniasis (sodium stibogluconate, sodium stibogluconate, amphotericin B and miltefosine). For buparvaquone, mean % inhibition in intracellular amastigotes at four different concentrations (1.35 µM, 0.51 µM, 0.17 µM and 0.057 µM) was 78%, 44%, 20% and 14% respectively, whereas, against promastigotes it was 89%, 77%, 45% and 35% respectively. IC50 values calculated to estimate the anti-leishmanial activity of buparvaquone against intra-cellular amastigotes and promastigotes was 0.53 µM (95% C.I. = 0.32-0.89) and 0.15 µM (95% C.I. = 0.01-1.84) respectively. Amphotericin B was the most potent in-vitro drug tested, with an IC50 of 0.075 µM (95% C.I. = 0.006-0.907) against promastigotes, and 0.065 µM (95% C.I. = 0.048-0.089) against intra-cellular amastigotes. Amphotericin B was more cytotoxic against THP1 cells, with an IC50 of 0.15 µM (95% C.I. = 0.01-0.95) and an apparent in-vitro therapeutic index of 2.0, than was buparvaquone, with an IC50 of 12.03 µM (95% C.I. = 5.36-26.96) against THP1 cells and a therapeutic index of 80.2. The study proposes that buparvaquone may be further investigated as a candidate drug for treatment of cutaneous leishmaniasis.
Department of Zoology, University of Peshawar, Peshawar, Pakistan. Electronic address: qaisar.jamal21@gmail.com.
Qaisar
Q
Jamal
Department of Zoology, University of Peshawar, Peshawar, Pakistan.
Nazma Habib
NH
Khan
Department of Zoology, University of Peshawar, Peshawar, Pakistan.
Sobia
S
Wahid
Department of Zoology, University of Peshawar, Peshawar, Pakistan.
Mahwish Mustafa
MM
Awan
Faculty of Infectious & Tropical Diseases, London School of Hygiene & Tropical Medicine, Keppel St, London WC1E 7HT, UK.
Colin
C
Sutherland
Department of Zoology, University of Peshawar, Peshawar, Pakistan.
Akram
A
Shah
D000666:Amphotericin B / Q000494:pharmacology / Q000633:toxicity; D000967:Antimony Sodium Gluconate / Q000494:pharmacology / Q000633:toxicity; D000981:Antiprotozoal Agents / Q000494:pharmacology* / Q000633:toxicity; D045744:Cell Line, Tumor / Q000187:drug effects; D002648:Child; D006801:Humans; D020128:Inhibitory Concentration 50; D007895:Leishmania tropica / Q000187:drug effects* / Q000254:growth & development; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy / Q000469:parasitology; D008264:Macrophages / Q000469:parasitology; D008297:Male; D008536:Meglumine / Q000494:pharmacology / Q000633:toxicity; D000077485:Meglumine Antimoniate; D009285:Naphthoquinones / Q000494:pharmacology* / Q000633:toxicity; D009942:Organometallic Compounds / Q000494:pharmacology / Q000633:toxicity; D010154:Pakistan; D021261:Parasitic Sensitivity Tests
D000981:Antiprotozoal Agents; D009285:Naphthoquinones; D009942:Organometallic Compounds; C046326:buparvaquone; D008536:Meglumine; D000077485:Meglumine Antimoniate; D000666:Amphotericin B; D000967:Antimony Sodium Gluconate
% inhibition; Buparvaquone; IC(50); KWH(23); Leishmania tropica