| Title: |
In-vitro antileishmanial potential of peptide drug hirudin. |
| Authors: |
Khan, Hanif1, Nadhman, Akhtar2 akhtar.nadhman@iiu.edu.pk, Azam, Syed Sikander3, Anees, Mariam1 mariam@qau.edu.pk, Khan, Imran2, Ullah, Ikram2, Sohail, Muhammad Farhan4, Shahnaz, Gul4, Yasinzai, Masoom2 |
| Source: |
Chemical Biology & Drug Design. Jan2017, Vol. 89 Issue 1, p67-73. 7p. |
| Subject Terms: |
*HIRUDIN, *LEISHMANIASIS treatment, *PROTEINASES, *MACROPHAGES, *CELL-mediated cytotoxicity, *THERAPEUTICS |
| Abstract: |
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 ( GP63), out of which hirudin exhibited higher binding affinity with GP63 and good expected IC50 values. Experimentally, hirudin showed most promising activity against promastigote and axenic amastigote forms of leishmanial parasites with IC50 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 LD50 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. [ABSTRACT FROM AUTHOR] |
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