Podophyllotoxin, Deoxypodophyllotoxin and Ursolic Acid as Potential Inhibitors of tcpA, ompW, and ctxB Genes in Vibrio cholerae: An in-Silico Study

Introduction: Cholera is a highly contagious disease that causes severe diarrhea and dehydration. This study investigated podophyllotoxin, deoxypodophyllotoxin, and ursolic acid as inhibitors of tcpA, ompW, and ctxB genes in Vibrio cholerae. Methods: We obtained the crystallized structure of pod...

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Main Authors: Yasin SarveAhrabi1*, Ovis Rostamiyan1, Sarina Nejati khoei1
Format: Article
Language:English
Published: Pasteur Institute of Iran 2023-03-01
Series:Journal of Medical Microbiology and Infectious Diseases
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author Yasin SarveAhrabi1*
Ovis Rostamiyan1
Sarina Nejati khoei1
author_facet Yasin SarveAhrabi1*
Ovis Rostamiyan1
Sarina Nejati khoei1
author_sort Yasin SarveAhrabi1*
collection DOAJ
description Introduction: Cholera is a highly contagious disease that causes severe diarrhea and dehydration. This study investigated podophyllotoxin, deoxypodophyllotoxin, and ursolic acid as inhibitors of tcpA, ompW, and ctxB genes in Vibrio cholerae. Methods: We obtained the crystallized structure of podophyllotoxin, deoxypodophyllotoxin, and ursolic acid from the PubChem database for use as a ligand. The mm2 method in Chem3D v20.1.1.125 was used to optimize the structure of the ligands. We used AutodackVina v.1.2.0 to evaluate the ligands as inhibitors against the active site of the tcpA, ompW, and ctxB proteins. The output results were analyzed and assessed by BIOVIA Discovery Studio 2016 V16.1.0 X64. Results: The reported affinities ranged from -6.8 and -8.7 kcal/mol. The highest diversity of links was found in tcpA and ctxB. Hydrogen bonds were established with Threonine (91, 111), Glycine (113, 114, 94), and Alanine (92) of tcpA, indicating the effectiveness of ligands against tcpA. The ligands podophyllotoxin, deoxypodophyllotoxin, and ursolic acid showed a variety of hydrogen bonds against ompW and ctxB, respectively, with Arginine, Isoleucine, Histidine, Glycine, and Glutamine. These results demonstrate the excellent inhibitory effects of the ligands against Vibrio cholerae. Conclusion: Vibrio cholerae plays a crucial role in causing pandemic cholera in humans. The predicted conformations of the ligands in this study showed that podophyllotoxin and deoxypodophyllotoxin have higher inhibitory potential than ursolic acid. Therefore, podophyllotoxin and deoxypodophyllotoxin can be potential agents for further research in developing Anti-Vibrio cholerae drugs.
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spelling doaj-art-1fe813ba3a7f4fa18a6bfe2e41fd76f42025-08-20T01:49:35ZengPasteur Institute of IranJournal of Medical Microbiology and Infectious Diseases2345-53492345-53302023-03-01111414810.52547/JoMMID.11.1.41Podophyllotoxin, Deoxypodophyllotoxin and Ursolic Acid as Potential Inhibitors of tcpA, ompW, and ctxB Genes in Vibrio cholerae: An in-Silico StudyYasin SarveAhrabi1*0https://orcid.org/0000-0001-7062-6963Ovis Rostamiyan11https://orcid.org/0000-0002-4362-5524Sarina Nejati khoei12https://orcid.org/0000-0001-9630-49111Department of Biology, Central Tehran Branch, Islamic Azad University, Tehran, Iran1Department of Biology, Central Tehran Branch, Islamic Azad University, Tehran, Iran1Department of Biology, Central Tehran Branch, Islamic Azad University, Tehran, IranIntroduction: Cholera is a highly contagious disease that causes severe diarrhea and dehydration. This study investigated podophyllotoxin, deoxypodophyllotoxin, and ursolic acid as inhibitors of tcpA, ompW, and ctxB genes in Vibrio cholerae. Methods: We obtained the crystallized structure of podophyllotoxin, deoxypodophyllotoxin, and ursolic acid from the PubChem database for use as a ligand. The mm2 method in Chem3D v20.1.1.125 was used to optimize the structure of the ligands. We used AutodackVina v.1.2.0 to evaluate the ligands as inhibitors against the active site of the tcpA, ompW, and ctxB proteins. The output results were analyzed and assessed by BIOVIA Discovery Studio 2016 V16.1.0 X64. Results: The reported affinities ranged from -6.8 and -8.7 kcal/mol. The highest diversity of links was found in tcpA and ctxB. Hydrogen bonds were established with Threonine (91, 111), Glycine (113, 114, 94), and Alanine (92) of tcpA, indicating the effectiveness of ligands against tcpA. The ligands podophyllotoxin, deoxypodophyllotoxin, and ursolic acid showed a variety of hydrogen bonds against ompW and ctxB, respectively, with Arginine, Isoleucine, Histidine, Glycine, and Glutamine. These results demonstrate the excellent inhibitory effects of the ligands against Vibrio cholerae. Conclusion: Vibrio cholerae plays a crucial role in causing pandemic cholera in humans. The predicted conformations of the ligands in this study showed that podophyllotoxin and deoxypodophyllotoxin have higher inhibitory potential than ursolic acid. Therefore, podophyllotoxin and deoxypodophyllotoxin can be potential agents for further research in developing Anti-Vibrio cholerae drugs.vibrio choleraeursolic acidpodophyllotoxintcpaompw
spellingShingle Yasin SarveAhrabi1*
Ovis Rostamiyan1
Sarina Nejati khoei1
Podophyllotoxin, Deoxypodophyllotoxin and Ursolic Acid as Potential Inhibitors of tcpA, ompW, and ctxB Genes in Vibrio cholerae: An in-Silico Study
Journal of Medical Microbiology and Infectious Diseases
vibrio cholerae
ursolic acid
podophyllotoxin
tcpa
ompw
title Podophyllotoxin, Deoxypodophyllotoxin and Ursolic Acid as Potential Inhibitors of tcpA, ompW, and ctxB Genes in Vibrio cholerae: An in-Silico Study
title_full Podophyllotoxin, Deoxypodophyllotoxin and Ursolic Acid as Potential Inhibitors of tcpA, ompW, and ctxB Genes in Vibrio cholerae: An in-Silico Study
title_fullStr Podophyllotoxin, Deoxypodophyllotoxin and Ursolic Acid as Potential Inhibitors of tcpA, ompW, and ctxB Genes in Vibrio cholerae: An in-Silico Study
title_full_unstemmed Podophyllotoxin, Deoxypodophyllotoxin and Ursolic Acid as Potential Inhibitors of tcpA, ompW, and ctxB Genes in Vibrio cholerae: An in-Silico Study
title_short Podophyllotoxin, Deoxypodophyllotoxin and Ursolic Acid as Potential Inhibitors of tcpA, ompW, and ctxB Genes in Vibrio cholerae: An in-Silico Study
title_sort podophyllotoxin deoxypodophyllotoxin and ursolic acid as potential inhibitors of tcpa ompw and ctxb genes in vibrio cholerae an in silico study
topic vibrio cholerae
ursolic acid
podophyllotoxin
tcpa
ompw
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AT ovisrostamiyan1 podophyllotoxindeoxypodophyllotoxinandursolicacidaspotentialinhibitorsoftcpaompwandctxbgenesinvibriocholeraeaninsilicostudy
AT sarinanejatikhoei1 podophyllotoxindeoxypodophyllotoxinandursolicacidaspotentialinhibitorsoftcpaompwandctxbgenesinvibriocholeraeaninsilicostudy