Repository of Research and Investigative Information

Repository of Research and Investigative Information

Hormozgan University of Medical Sciences

Promising antileishmanial activity of novel imidazole antifungal drug Luliconazole against Leishmania major: in vitro and in silico studies

(2018) Promising antileishmanial activity of novel imidazole antifungal drug Luliconazole against Leishmania major: in vitro and in silico studies. Journal of global antimicrobial resistance.

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Official URL: https://www.ncbi.nlm.nih.gov/pubmed/29793051

Abstract

OBJECTIVES Pentavalent antimonials have been used for the treatment of leishmaniasis for more than 70 years; however their toxicity limits their benefits. Unfortunately, the efficacy of the first line drugs has been decreased and resistance seems to be noticeable. Luliconazole is a new azole with unique effects on fungi which has not been tested on Leishmania parasites yet. METHODS In the present study, we evaluated cytotoxicity and anti-leishmanial activities of Luliconazole on promastigotes and intracellular amastigotes of Leishmania major (L. major) in vitro. In addition, the 3D structure of Luliconazole was prepared by ACD ChemSketch 11 Software. RESULTS Our results on promastigotes revealed that Luliconazole with IC value of 0.19μM has greatly higher potency than Ketoconazole (KCZ), Meglumine Antimoniate (MA) and Amphotericin B (AmB) (IC=135μM, 538μM and 2.52μM). In amastigote stage, at the dose of 0.07μM, Luliconazole decreased the mean infection rate (MIR) and the mean number of amastigotes per macrophages (MNAPM) more effectively than MA (p<0.004) and KCZ (p<0.043) but there was no different association with AmB (p>0.05). Docking study of Luliconazole with cytochrome P450 sterol 14α-demethylase (PDB code: 3L4D) revealed that this azole drug can properly interact with the target enzyme in Leishmania mainly via coordination with the heme and multiple hydrophobic interactions. CONCLUSION These results showed the potent activity of Luliconazole in extremely low concentration against L. major; therefore, it could be considered as a new candidate for treatment of leishmaniasis in the close future.

Item Type: Article
Keywords: Leishmania major,Luliconazole,anti-leishmanial activity,in silico study
Subjects: QV Pharmacology > QV 701-835 Pharmacy and Pharmaceutics
WC Communicable Diseases > WC 450-475 Mycoses
Divisions: Research Vice-Chancellor Department > Infectious and Tropical Diseases Research Center
Depositing User: مهندس هدی فهیم پور
URI: http://eprints.hums.ac.ir/id/eprint/5741

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