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In Silico Screening of DNA Gyrase B Potent Flavonoids for the Treatment of Clostridium difficile Infection from PhytoHub Database
Verma, Kanika; Mahalapbutr, Panupong; Suriya, Utid; Somboon, Tuanjai; Aiebchun, Thitinan; Shi, Liyi; Maitarad, Phornphimon; Rungrotmongkol, Thanyada.
Afiliação
  • Verma, Kanika; Chulalongkorn University. Faculty of Science. Department of Biochemistry. Bangkok. TH
  • Mahalapbutr, Panupong; Khon Kaen University. Faculty of Medicine. Department of Biochemistry. Khon Kaen. TH
  • Suriya, Utid; Chulalongkorn University. Faculty of Science. Program in Biotechnology. Bangkok. TH
  • Somboon, Tuanjai; Chulalongkorn University. Faculty of Science. Department of Biochemistry. Bangkok. TH
  • Aiebchun, Thitinan; Chulalongkorn University. Faculty of Science. Department of Biochemistry. Bangkok. TH
  • Shi, Liyi; Shanghai University. College of Sciences. Department of Chemistry. Shanghai. CN
  • Maitarad, Phornphimon; Shanghai University. Research Center of Nano Science and Technology. Baoshan district. CN
  • Rungrotmongkol, Thanyada; Chulalongkorn University. Faculty of Science. Department of Biochemistry. Bangkok. TH
Braz. arch. biol. technol ; Braz. arch. biol. technol;64: e21200402, 2021. tab, graf
Article em En | LILACS | ID: biblio-1249214
Biblioteca responsável: BR1.1
ABSTRACT
Abstract Clostridium difficile infection (CDI) is the most common hospital acquired diarrheal disease with its increasing incidence and mortality rate globally. DNA Gyrase B (GyrB) is a key component of DNA replication process across all bacterial genera; thus, this offers a potential target for the treatment of CDI. In the present study, several virtual screening approaches were employed to identify a novel C. difficile GyrB inhibitor. The 139 known metabolites were screened out from the 480 flavonoids in PhytoHub database. Molinspiration and PROTOX II servers were used to calculate the ADME properties and oral toxicity of the metabolites, whereas mutagenicity, tumorigenicity, irritant, and reproductive effect were predicted using DataWarrior program. The binding mode and the binding efficiency of the screened flavonoids against the GyrB were studied using FlexX docking program. From virtual screening of 139 metabolites, we found 25 flavonoids with no mutagenicity, tumorigenicity, irritant, and reproductive effect. Docking study suggested that flavonoids 1030 ((-)-epicatechin 3'-O-sulfate), 1032 ((-)-epicatechin 4'-O-sulfate), 1049 (3'-O-methyl-(-)-epicatechin 4-O-sulfate), 1051 (3'-O-methyl-(-)-epicatechin 7-O-sulfate), 1055 (4'-O-methyl-(-)-epicatechin 7-O-sulfate) and 1317 (quercetin sulfate) have significantly higher binding affinity than the known GyrB inhibitor novobiocin. The results from molecular dynamics simulation and free energy calculations based on solvated interaction energy suggested that (-)-epicatechin 3'-O-sulfate could be a potential drug candidate in the management of CDI.
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Texto completo: 1 Coleções: 01-internacional Base de dados: LILACS Assunto principal: Flavonoides / Infecções por Clostridium / DNA Girase Tipo de estudo: Diagnostic_studies / Screening_studies Idioma: En Revista: Braz. arch. biol. technol Assunto da revista: BIOLOGIA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: China / Tailândia País de publicação: Brasil
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Texto completo: 1 Coleções: 01-internacional Base de dados: LILACS Assunto principal: Flavonoides / Infecções por Clostridium / DNA Girase Tipo de estudo: Diagnostic_studies / Screening_studies Idioma: En Revista: Braz. arch. biol. technol Assunto da revista: BIOLOGIA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: China / Tailândia País de publicação: Brasil