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Thiazine-derived compounds in inhibiting efflux pump in Staphylococcus aureus K2068, mepA gene expression, and membrane permeability alteration.
Freitas, Priscilla R; de Araújo, Ana C J; Araújo, Isaac M; de Almeida, Ray S; Borges, João A O; Paulo, Cícera L R; Oliveira-Tintino, Cícera D M; Miranda, Gustavo M; Araújo-Neto, José B; Nascimento, Igor J S; Araújo-Júnior, João X; Silva, Julia M A; Balbino, Tereza C L; Silva-Júnior, Edeildo F; Aquino, Thiago M; Mendonca-Junior, Franscisco J B; Marinho, Emmanuel S; Santos, Hélcio S; Lima, Clara Mariana Gonçalves; Obaidullah, Ahmad J; Bin Emran, Talha; Cunha, Francisco A B; Menezes, Irwin R A; Tintino, Saulo R; Coutinho, Henrique D M.
Afiliación
  • Freitas PR; Department of Biological Chemistry, Universidade Regional do Cariri, Crato-CE, Brazil.
  • de Araújo ACJ; Department of Biological Chemistry, Universidade Regional do Cariri, Crato-CE, Brazil.
  • Araújo IM; Department of Biological Chemistry, Universidade Regional do Cariri, Crato-CE, Brazil.
  • de Almeida RS; Department of Biological Chemistry, Universidade Regional do Cariri, Crato-CE, Brazil.
  • Borges JAO; Department of Biological Chemistry, Universidade Regional do Cariri, Crato-CE, Brazil.
  • Paulo CLR; Department of Biological Chemistry, Universidade Regional do Cariri, Crato-CE, Brazil.
  • Oliveira-Tintino CDM; Department of Biological Chemistry, Universidade Regional do Cariri, Crato-CE, Brazil.
  • Miranda GM; Instituto Gonçalo Moniz (IGM) - Fiocruz Bahia, Brazil.
  • Araújo-Neto JB; Postgraduate Program in Biological Sciences, Biosciences Center, Federal University of Pernambuco, Recife, PE 50740-570, Brazil.
  • Nascimento IJS; Laboratory of Medicinal Chemistry, Institute of Pharmaceutical Sciences, Federal University of Alagoas, Maceió, AL 57072-900, Brazil.
  • Araújo-Júnior JX; Laboratory of Medicinal Chemistry, Institute of Pharmaceutical Sciences, Federal University of Alagoas, Maceió, AL 57072-900, Brazil.
  • Silva JMA; Department of Microbiology, Aggeu Magalhães Institute, Oswaldo Cruz Foundation (Fiocruz), Recife, Brazil.
  • Balbino TCL; Department of Microbiology, Aggeu Magalhães Institute, Oswaldo Cruz Foundation (Fiocruz), Recife, Brazil.
  • Silva-Júnior EF; Biological and Molecular Chemistry Research Group, Institute of Chemistry and Biotechnology, Federal University of Alagoas, Maceió, AL 57072-900, Brazil.
  • Aquino TM; Biological and Molecular Chemistry Research Group, Institute of Chemistry and Biotechnology, Federal University of Alagoas, Maceió, AL 57072-900, Brazil.
  • Mendonca-Junior FJB; Laboratory of Synthesis and Drug Delivery-LSVM, Paraiba State University, João Pessoa, PB 58071-160, Brazil.
  • Marinho ES; Laboratory of Chemistry of Natural and Synthetic Product, State University of Ceará, UECE, Fortaleza, CE 60741-835, Brazil.
  • Santos HS; Laboratory of Chemistry of Natural and Synthetic Product, State University of Ceará, UECE, Fortaleza, CE 60741-835, Brazil.
  • Lima CMG; Department of Food Science, Federal University of Lavras, Lavras, Minas Gerais CEP 37200-900, Brazil.
  • Obaidullah AJ; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia. Electronic address: aobaidullah@ksu.edu.sa.
  • Bin Emran T; Department of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, RI 02912, USA; Legorreta Cancer Center, Brown University, Providence, RI 02912, USA; Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, 
  • Cunha FAB; Department of Biological Chemistry, Universidade Regional do Cariri, Crato-CE, Brazil.
  • Menezes IRA; Department of Biological Chemistry, Universidade Regional do Cariri, Crato-CE, Brazil.
  • Tintino SR; Department of Biological Chemistry, Universidade Regional do Cariri, Crato-CE, Brazil.
  • Coutinho HDM; Department of Biological Chemistry, Universidade Regional do Cariri, Crato-CE, Brazil. Electronic address: hdmcoutinho@gmail.com.
Biomed Pharmacother ; 179: 117291, 2024 Aug 14.
Article en En | MEDLINE | ID: mdl-39146766
ABSTRACT
Staphylococcus aureus is a bacterium responsible for resistance to multiple drugs and the efflux system is widely studied among the resistance mechanisms developed by this species. The present study evaluates the inhibition of the MepA efflux pump by thiadiazine-derived compounds. For this purpose, thiadiazine-derived compounds (IJ-14 to IJ-20) were tested against S. aureus K2068 strains. Microdilution tests were initially conducted to assess the Minimum Inhibitory Concentration (MIC) of the compounds and their efflux pump inhibition activity. In addition, fluorimetry tests were performed using BrEt emission and tests were conducted to inhibit the expression of the mepA gene. This involved comparing the bacterial gene expression with the antibiotic alone to the gene expression after combining compounds (IJ-17 and IJ-20) with the antibiotic. Furthermore, membrane permeability assessment tests and in silico molecular docking tests were performed. It was observed that the IJ17 and IJ20 compounds exhibited direct activity against the tested strain. The IJ17 compound produced significant results in the gene inhibition tests, which was also evidenced through the membrane permeability alteration test. These findings suggest that thiadiazine-derived compounds have promising effects against one of the main resistance mechanisms, with the IJ17 compound presenting observable mechanisms of action.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Biomed Pharmacother Año: 2024 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Francia
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Biomed Pharmacother Año: 2024 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Francia