Abstract
Cutaneous leishmaniasis affects nearly 0.7 to 1.3 million people annually. Treatment of this disease is difficult due to lack of appropriate medication and the growing problem of drug resistance. Natural compounds such as coumarins serve as complementary therapeutic agents in addition to the current treatment modalities. In this study, we have performed an in-silico screening of the coumarin derivatives and their anti-leishmanial properties has been explored both in-vitro and in-vivo. One of the compounds (compound 2) exhibited leishmanicidal activity and to further study its properties, nanoliposomal formulation of the compound was developed. Treatment of cutaneous lesions in BALB/c mice with compound 2 showed significantly reduced lesion size as compared to the untreated mice (p<0.05) suggesting that compound 2 may possess anti-leishmanial properties.
Highlights
Leishmaniasis is a neglected tropical disease that is caused by the parasite ‘Leishmania’
In our computational screening procedure, we have identified a set of five compounds which were screened for their anti-leishmanial properties
Coumarin derivatives obtained from the ZINC database were further screened based on their compliance with the Lipinski’s rule of five and Veber’s rules
Summary
Leishmaniasis is a neglected tropical disease that is caused by the parasite ‘Leishmania’. There are three forms of leishmaniasis, namely cutaneous, mucocutaneous and visceral forms. Cutaneous leishmaniasis (CL) is more wide spread and has an higher incidence that the visceral form. Treatment of CL is usually done by administration of antimony based compounds (sodium stibogluconate and meglumine antimoniate) in the form of intramuscular injections. [1] Second line chemotherapy is focusing on oral anti-fungal compounds, liposomal formulations (Amphotericin B) and topical formulations of paromomycin (Leshcutan). Liposomal amphotericin B (Ambiosome) is being used for treatment of CL incase of drug resitance to the existing antimonials. Amphotericin B has been shown to be effective against all forms of leishmaniasis, the liposomal formulation proves to be expensive, has a lower therapeutic index and is difficult to administer. Amphotericin B has been shown to be effective against all forms of leishmaniasis, the liposomal formulation proves to be expensive, has a lower therapeutic index and is difficult to administer. [2] Paromomycin and Pentamidine are some other compounds that show good efficacy to PLOS ONE | DOI:10.1371/journal.pone.0164585 October 21, 2016
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