Premium
In‐vitro antileishmanial potential of peptide drug hirudin
Author(s) -
Khan Hanif,
Nadhman Akhtar,
Azam Syed Sikander,
Anees Mariam,
Khan Imran,
Ullah Ikram,
Sohail Muhammad Farhan,
Shahnaz Gul,
Yasinzai Masoom
Publication year - 2017
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12831
Subject(s) - hirudin , pharmacology , in vitro , amastigote , chemistry , cytotoxicity , drug , leishmania , biology , biochemistry , immunology , parasite hosting , thrombin , platelet , world wide web , computer science
Hirudin is clinically an important drug used for the treatment of cardiac diseases, but has never been elucidated for antileishmanial potential. This study was designed to determine the therapeutic utility of hirudin against leishmaniasis. Binding affinities of 28 potent proteinase inhibitors were screened computationally against leishmanolysin ( GP 63), out of which hirudin exhibited higher binding affinity with GP 63 and good expected IC 50 values. Experimentally, hirudin showed most promising activity against promastigote and axenic amastigote forms of leishmanial parasites with IC 50 values of 0.60 ± 0.36 μg/mL and 0.43 ± 0.23 μg/mL, respectively, in a dose‐ and time‐dependent assay. The cytotoxicity assay revealed no adverse effects on human macrophages with LD 50 value of 860.11 ± 53.44 μg/mL. Hirudin caused leishmanial cell death mainly by apoptosis and membrane permeability. In spite of the basic knowledge obtained, hirudin mechanism is considerably less prone to the induction of resistance than classical drugs. Collectively, this study fosters further studies for the hirudin as new antileishmania lead with a new mode of action.