title: In silico and in vitro comparative activity of novel experimental derivatives against Leishmania major and Leishmania infantum promastigotes.
abstract: This in silico and in vitro comparative study was designed to evaluate the effectiveness of some biurets (K1 to K8) and glucantime against Leishmania major and Leishmania infantum promastigotes. Overall, eight experimental ligands and glucantime were docked using AutoDock 4.3 program into the active sites of Leishmania major and Leishmania infantum pteridine reductase 1, which were modeled using homology modeling programs. The colorimetric MTT assay was used to find L. major and L. infantum promastigotes viability at different concentrations of biuret derivatives in a concentration and time-dependent manner and the obtained results were expressed as 50% and 90% of inhibitory concentration (IC₅₀ and IC₉₀). In silico method showed that out of eight experimental ligands, four compounds were more active on pteridine reductase 1. K3 was the most active against L. major promastigotes with an IC₅₀ of 6.8 μM and an IC₉₀ of 40.2 μM, whereas for L. infantum promastigotes was K8 with IC₅₀ of 7.8 μM. The phenylethyl derivative (K7) showed less toxicity (IC₅₀s>60 μM) in both Leishmania strains. Glucantime displayed less growth inhibition in concentration of about 20 μM. In silico and especially docking results in a recent study were in accordance with the in vitro activity of these compounds in presented study and compound K3, K2 and K8 showed reasonable levels of selectivity for the Leishmania pteridine reductase 1.
authors.affiliation: Department of Medical Parasitology, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
authors.forename: Shahram
authors.initials: S
authors.lastname: Khademvatan
authors.forename: Neda
authors.initials: N
authors.lastname: Adibpour
authors.forename: Alborz
authors.initials: A
authors.lastname: Eskandari
authors.forename: Saeed
authors.initials: S
authors.lastname: Rezaee
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Hashemitabar
authors.forename: Fakher
authors.initials: F
authors.lastname: Rahim
mesh_terms: D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology*; D001737:Biuret / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D003124:Colorimetry; D018314:Leishmania infantum / Q000166:cytology / Q000187:drug effects*; D018320:Leishmania major / Q000166:cytology / Q000187:drug effects*; D008536:Meglumine / Q000494:pharmacology; D000077485:Meglumine Antimoniate; D009942:Organometallic Compounds / Q000494:pharmacology; D010802:Phylogeny
chemical_list: D000981:Antiprotozoal Agents; D009942:Organometallic Compounds; D008536:Meglumine; D000077485:Meglumine Antimoniate; D001737:Biuret
keywords: Antileishmanial activity; Biurets; In silico; In vitro; MTT