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A Study On The Effectiveness Of Biurets And Glucantime Against Leighmania

2073 words - 9 pages

Background: Leishmaniasis is a complex protozoan disease comprises a wide range of clinical manifestations that is usually divided into visceral leishmaniasis, cutaneous leishmaniasis, and muco-cutaneous leishmaniasis depending on leishmania parasite strains and host's immune system responses. Most of the drugs produced for the treatment of leishmanial, from the first used (Glucantime and pentostam) to the lately accepted (miltefosine), are toxic, resistance issues and poorly tolerated. The purpose of this In Silico and In vitro study is evaluating the effectiveness of some novel experimental biurets and Glucantime against Leishmania tropica promastigotes.
Materials and methods: In general, eight experimental biuret compounds and glucantime (reference drug) were docked into the active sites of L. tropica pteridine reductase 1, using AutoDock 4.3 software which was modeled by homology modeling programs. promastigote stages of L. tropica (MHOM/IR/02/Mash10) were transferred to RPMI-1640medium, supplemented with 10% FCS and antibiotics then grown at 25±2°C. We used MTT assay to find viability of L. tropica promastigotes at wide range concentrations of biuret compounds and the achieved results were explicated as 50 and 90 percent of inhibitory concentration (IC50 and IC90). All experiments were performed in triplicate.
Results: In Silico Procedure shown that from the eight selected experimental biurets, four ligands showed highly active on PTR1. K8 and K3 were the most active against L. tropica promastigote with IC50s of 1.23 μM and 3.1 μM after 72 h respectively .The K6 showed less toxicity with IC50 more than 60μM. Glucantime displayed less growth inhibition with IC50 of 45.65μM.
Conclusion: In silico consequences in present study were in agreement with the in vitro activity of the compounds and compound K8, K3, and K4 showed rational levels of selectivity for the PTR1. This study also showed desirable in vitro activity of biuret derivatives against Leishmania promastigotes that could be exploited as a potential antileishmanial agent but anti-amastigote and in vivo activities of these compounds should be study.
Keywords: Biuret, antileishmanial activity, MTT, In vitro and In Silico

1. Introduction
leishmaniasis is a protozoan parasitic disease that is distributed worldwide and found especially in parts of the tropics, subtropics, and southern Europe. Leishmaniasis is caused by infection with genus Leishmania parasite, which is spread by the bite of infected sand flies. There are several different clinical forms of leishmaniasis in people. Cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL) are the most common forms are, which cause skin sores and affect several internal organs (usually spleen, liver, and bone marrow) respectively. Leishmaniasis displays a major worldwide health problem in most developing countries. CL is endemic in at least 82 countries and estimated that it afflicts about 10 million people and its annual...

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