Synergistic effect of new pyrimidine derivative with oxacilin against methicillin-resistant Staphylococcus aureus .

Autor: de Oliveira Silva BK; Postgraduate Program in Pharmaceutical Sciences-Federal University of Pernambuco, Av. Prof. Moraes Rego, 1235 - University City, Recife, PE,  50740-560, Brazil., do Monte ZS; Postgraduate Program in Pharmaceutical Sciences-Federal University of Pernambuco, Av. Prof. Moraes Rego, 1235 - University City, Recife, PE,  50740-560, Brazil., Santos Costa EC; Postgraduate Program in Biological Sciences, Federal University of Pernambuco, Recife, PE,  50740-560, Brazil., Silva RO; Department of Fundamental Chemistry, Federal University of Pernambuco, Av. Prof. Moraes Rego, 1235 - University City, Recife, PE,  50740-560, Brazil., Souza NF; Laboratory of Cheminformatics, Program of Natural & Synthetic Bioactive Products (PgPNSB), Health Sciences Center Federal University of Paraíba, Campus I Lot. Cidade Universitaria, João Pessoa, PB,  58051-900, Brazil., Barros Menezes RP; Laboratory of Cheminformatics, Program of Natural & Synthetic Bioactive Products (PgPNSB), Health Sciences Center Federal University of Paraíba, Campus I Lot. Cidade Universitaria, João Pessoa, PB,  58051-900, Brazil., Scotti MT; Laboratory of Cheminformatics, Program of Natural & Synthetic Bioactive Products (PgPNSB), Health Sciences Center Federal University of Paraíba, Campus I Lot. Cidade Universitaria, João Pessoa, PB,  58051-900, Brazil., Scotti L; Laboratory of Cheminformatics, Program of Natural & Synthetic Bioactive Products (PgPNSB), Health Sciences Center Federal University of Paraíba, Campus I Lot. Cidade Universitaria, João Pessoa, PB,  58051-900, Brazil., de Souza Lima GM; Department of Antibiotic, Federal University of Pernambuco, Av. Prof. Moraes Rego, 1235 - University City, Recife, PE,  50740-560, Brazil., de Melo SJ; Postgraduate Program in Pharmaceutical Sciences-Federal University of Pernambuco, Av. Prof. Moraes Rego, 1235 - University City, Recife, PE,  50740-560, Brazil.; Postgraduate Program in Biological Sciences, Federal University of Pernambuco, Recife, PE,  50740-560, Brazil.
Jazyk: angličtina
Zdroj: Future medicinal chemistry [Future Med Chem] 2024 Sep 05, pp. 1-14. Date of Electronic Publication: 2024 Sep 05.
DOI: 10.1080/17568919.2024.2385887
Abstrakt: Aim: This work aimed to synthesize a new pyrimidine PYB01 with potential application against antimicrobial resistance. Materials & methods: PYB01 was synthesized through condensation reaction between 3a and 3b . The antimicrobial evaluation was carried out using the microdilution method in Mueller-Hinton Agar and in silico predictions using different software. Results: PYB01 has moderate antibiotic activity and high capacity to efficiently modulate antibiotic resistance in Staphylococcus aureus . In silico evaluations demonstrated that PYB01 is probably an allosteric inhibitor of Protein Binding Penicilin 2a and modulates the action of oxacillin by decreasing the minimum inhibitory concentration by 64-times. PYB01 demonstrate a good pharmacokinetic profile and toxicological. Conclusion: PYB01 has great potential to go further in investigating its use against antimicrobial resistance.
Databáze: MEDLINE