Affiliation:
1. Department of Biotechnology, Lyallpur Khalsa College, Jalandhar, India
Abstract
Background:
Glucosinolates (β-thioglucoside-N-hydroxysulfates) are a water-soluble organic
anion with sulfur- and nitrogen-containing glycosides which are found in abundance in Cruciferous
plants. Ergosterol (ERG13) lanosterol-14α-demethylase protein has been targeted for inhibition
studies as a key regulator enzyme of fungal membrane biosynthesis.
Objectives:
To understand the molecular mechanism of inhibition of Ergosterol (ERG13) lanosterol-
14α-demethylase by various phytochemicals from brassicales, i.e., glucosinolates and their potential
role as putative drug molecules.
Methodology:
In this study, in silico analyses were performed to predict the molecular basis of various
glucosinolates as a potential inhibitor of lanosterol-14α-demethylase protein, which is a key regulator
of fungal membrane biosynthesis and its pharmacodynamics and toxicity profile. 3d structures of various
glucosinolates were retrieved from PubChem, and the target protein, lanosterol-14α-demethylase
(Pdb ID- 4lxj), was retrieved from the RCSB protein data bank. Molecular docking and interactions
were carried out using the PyRx software using the AutoDOCK toolbar with default parameters. Dru-
LiTo, ORISIS web servers were used to predict various drug likeliness predictions and Lipinski’s Rule
of 5, whereas admetSAR was used for prediction of toxicity, and PASS Program was used to study the
antifungal and antimicrobial properties of these compounds.
Results:
This study shows that among the different compounds screened, gluconasturtiin, Glucotropaeolin,
and Indolylmethyl-Glucosinolate showed the highest binding energies of -8.7 kcal/mol, -8.5
kcal/mol, and -8.3 kcal/mol with the lanosterol-14α-demethylase, respectively. Further all the compounds
follow the Lipinski’s rule as well as they are found to be non-carcinogenic and non-cytotoxic
in nature. These compounds also show antifungal properties.
Conclusion:
This study thus reveals that various glucosinolates interact with the ERG13 enzyme at
various amino acid positions, which behaves as a catalytic site, thus indicates the probable mechanism
of inactivation, and subsequently, these can be used as potential drug molecules. In vitro studies can be
taken to further examine the utility of these compounds as antifungal agents.
Publisher
Bentham Science Publishers Ltd.
Cited by
1 articles.
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