title: In-vitro antileishmanial potential of peptide drug hirudin.
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 IC50values. Experimentally, hirudin showed most promising activity against promastigote and axenic amastigote forms of leishmanial parasites with IC50values 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 LD50value 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.
authors.affiliation: Department of Biochemistry, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Hanif
authors.initials: H
authors.lastname: Khan
authors.affiliation: Sulaiman Bin Abdullah Aba Al-Khail - Centre for Interdisciplinary Research in Basic Sciences (SA-CIRBS), International Islamic University, Islamabad, Pakistan.
authors.forename: Akhtar
authors.initials: A
authors.lastname: Nadhman
authors.affiliation: Computational Biology Lab, National Center for Bioinformatics, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Syed Sikander
authors.initials: SS
authors.lastname: Azam
authors.affiliation: Department of Biochemistry, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Mariam
authors.initials: M
authors.lastname: Anees
authors.affiliation: Sulaiman Bin Abdullah Aba Al-Khail - Centre for Interdisciplinary Research in Basic Sciences (SA-CIRBS), International Islamic University, Islamabad, Pakistan.
authors.forename: Imran
authors.initials: I
authors.lastname: Khan
authors.affiliation: Sulaiman Bin Abdullah Aba Al-Khail - Centre for Interdisciplinary Research in Basic Sciences (SA-CIRBS), International Islamic University, Islamabad, Pakistan.
authors.forename: Ikram
authors.initials: I
authors.lastname: Ullah
authors.affiliation: Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Muhammad Farhan
authors.initials: MF
authors.lastname: Sohail
authors.affiliation: Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Gul
authors.initials: G
authors.lastname: Shahnaz
authors.affiliation: Sulaiman Bin Abdullah Aba Al-Khail - Centre for Interdisciplinary Research in Basic Sciences (SA-CIRBS), International Islamic University, Islamabad, Pakistan.
authors.forename: Masoom
authors.initials: M
authors.lastname: Yasinzai
mesh_terms: D000818:Animals; D006629:Hirudins / Q000494:pharmacology*; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D007891:Leishmania / Q000187:drug effects*; D062105:Molecular Docking Simulation
chemical_list: D006629:Hirudins
keywords: 
  Leishmania
  ; apoptosis; glucantime; hirudin; promastigote