AI Article Synopsis
- Hirudin, a drug commonly used for cardiac diseases, has not been previously explored for its potential to treat leishmaniasis, prompting this study.
- The research found that hirudin has a strong binding affinity to leishmanolysin and shows significant effectiveness against both promastigote and axenic amastigote forms of leishmanial parasites, with low cytotoxicity to human cells.
- Hirudin primarily kills leishmanial cells through apoptosis and increased membrane permeability, suggesting it may be less likely to induce drug resistance compared to traditional treatments, highlighting its potential as a new antileishmania agent.
Article 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 IC values. Experimentally, hirudin showed most promising activity against promastigote and axenic amastigote forms of leishmanial parasites with IC 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 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.
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| http://dx.doi.org/10.1111/cbdd.12831 | DOI Listing |
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