Virtual Screening of Henna Compounds Library for Discovery of New Leads against Human Thymidine Phosphorylase, an Overexpressed Factor of Hand-Foot Syndrome
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Published:2019-05-24
Issue:6
Volume:16
Page:625-636
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ISSN:1570-1808
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Container-title:Letters in Drug Design & Discovery
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language:en
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Short-container-title:LDDD
Author:
Khodabakhshi-Javinani Davood1, Ebrahim-Habibi Azadeh2, Afshar Minoo3, Navidpour Latifeh1
Affiliation:
1. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 14176, Iran 2. Biosensor Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran 3. Department of pharmaceutics, Faculty of Pharmacy and Pharmaceutical Sciences, Tehran Medical Sciences, Islamic Azad University, Tehran 193956466, Iran
Abstract
Background:
Capecitabine is one of the most effective and successful drugs for the
treatment of uterine and colorectal cancer which has been limited in use due to occurrence of handfoot
syndrome (HFS). Overexpression of human thymidine phosphorylase enzyme is predicted to be
one of the main causes of this syndrome. Thymidine phosphorylase enzyme is involved in many
cancers and inflammatory diseases and pyrimidine nucleoside phosphorylase family is found in a
variety of organisms. Results of clinical studies have shown that topical usage of henna plant
(Lawsonia inermis from the family of Lythraceae) could reduce the severity of HFS.
Methods:
By using in silico methods on reported compounds of henna, the present study is aimed at
finding phytochemicals and chemical groups with the potential to efficiently interact with and inhibit
human thymidine phosphorylase. Various compounds (825) of henna from different chemical groups
(138) were virtually screened by the interface to AutoDock in YASARA Software package, against the
enzyme structure obtained from X-ray crystallography and refined by homology modeling methods.
Results:
By virtual screening, i.e. docking of candidate ligands into the determined active site of hTP,
followed by applying the scoring function of binding affinity, 71 compounds (out of 825 compounds)
were estimated to have the likelihood to bind to the protein with an interaction energy higher than 10
kcal/mol (Concerning the sign of “binding energies”, please refer to the Methods section).
Conclusion:
Finally, diosmetin-3'-O-β-D-glucopyranoside (#219) and monoglycosylated naphthalene
were respectively selected as the most potent phytochemicals and chemical groups. Flavonoid-like
compounds with appropriate interaction energy were also considered as the most probable inhibitors.
More investigations on henna compounds, are needed in order to approve their effectiveness and also
to explore more anti-cancer, anti-inflammatory, anti-angiogenesis and even antibiotics.
Funder
Science and Technology project of Chongqing Education Commission Chongqing University Natural Science Foundation of Chongqing National Natural Science Foundation of China
Publisher
Bentham Science Publishers Ltd.
Subject
Drug Discovery,Pharmaceutical Science,Molecular Medicine
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