کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6291140 1302479 2013 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Evaluation of a diospyrin derivative as antileishmanial agent and potential modulator of ornithine decarboxylase of Leishmania donovani
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی انگل شناسی
پیش نمایش صفحه اول مقاله
Evaluation of a diospyrin derivative as antileishmanial agent and potential modulator of ornithine decarboxylase of Leishmania donovani
چکیده انگلیسی
World health organization has called for academic research and development of new chemotherapeutic strategies to overcome the emerging resistance and side effects exhibited by the drugs currently used against leishmaniasis. Diospyrin, a bis-naphthoquinone isolated from Diospyros montana Roxb., and its semi-synthetic derivatives, were reported for inhibitory activity against protozoan parasites including Leishmania. Presently, we have investigated the antileishmanial effect of a di-epoxide derivative of diospyrin (D17), both in vitro and in vivo. Further, the safety profile of D17 was established by testing its toxicity against normal macrophage cells (IC50 ∼ 20.7 μM), and also against normal BALB/c mice in vivo. The compound showed enhanced activity (IC50 ∼ 7.2 μM) as compared to diospyrin (IC50 ∼ 12.6 μM) against Leishmania donovani promastigotes. Again, D17 was tested on L. donovani BHU1216 isolated from a sodium stibogluconate-unresponsive patient, and exhibited selective inhibition of the intracellular amastigotes (IC50 ∼ 0.18 μM). Also, treatment of infected BALB/c mice with D17 at 2 mg/kg/day reduced the hepatic parasite load by about 38%. Subsequently, computational docking studies were undertaken on selected enzymes of trypanothione metabolism, viz. trypanothione reductase (TryR) and ornithine decarboxylase (ODC), followed by the enzyme kinetics, where D17 demonstrated non-competitive inhibition of the L. donovani ODC, but could not inhibit TryR.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Parasitology - Volume 135, Issue 2, October 2013, Pages 407-413
نویسندگان
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