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
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
انگل شناسی
پیش نمایش صفحه اول مقاله
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 â¼Â 20.7 μM), and also against normal BALB/c mice in vivo. The compound showed enhanced activity (IC50 â¼Â 7.2 μM) as compared to diospyrin (IC50 â¼Â 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 â¼Â 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
Journal: Experimental Parasitology - Volume 135, Issue 2, October 2013, Pages 407-413
نویسندگان
Sudipta Hazra, Subhalakshmi Ghosh, Madhushree Das Sarma, Smriti Sharma, Mousumi Das, Prakash Saudagar, Vijay Kumar Prajapati, Vikash Kumar Dubey, Shyam Sundar, Banasri Hazra,