QSAR Studies, Synthesis, and Biological Evaluation of New Pyrimido-Isoquinolin-Quinone Derivatives against Methicillin-Resistant Staphylococcus aureus

According to the WHO, antimicrobial resistance is among the top 10 threats to global health. Due to increased resistance rates, an increase in the mortality and morbidity of patients has been observed, with projections of more than 10 million deaths associated with infections caused by antibacterial...

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Published in:Pharmaceuticals (Basel, Switzerland) Switzerland), 2023-11, Vol.16 (11), p.1621
Main Authors: Andrades-Lagos, Juan, Campanini-Salinas, Javier, Sabadini, Gianfranco, Andrade, Victor, Mella, Jaime, Vásquez-Velásquez, David
Format: Article
Language:English
Subjects:
3D-QSAR
antibacterial agents
Antibiotics
Antimicrobial agents
Bacteria
Biological activity
CoMFA
Computational chemistry
drug discovery
Drug resistance
GDP
Global health
Gross Domestic Product
Hydrocarbons
Hydrogen bonds
Microorganisms
quinone antibiotics
R&D
Research & development
Staphylococcus infections
structure-activity relationships
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Summary:According to the WHO, antimicrobial resistance is among the top 10 threats to global health. Due to increased resistance rates, an increase in the mortality and morbidity of patients has been observed, with projections of more than 10 million deaths associated with infections caused by antibacterial resistant microorganisms. Our research group has developed a new family of pyrimido-isoquinolin-quinones showing antibacterial activities against multidrug-resistant Staphylococcus aureus. We have developed 3D-QSAR CoMFA and CoMSIA studies (r2 = 0.938; 0.895), from which 13 new derivatives were designed and synthesized. The compounds were tested in antibacterial assays against methicillin-resistant Staphylococcus aureus and other bacterial pathogens. There were 12 synthesized compounds active against Gram-positive pathogens in concentrations ranging from 2 to 32 µg/mL. The antibacterial activity of the derivatives is explained by the steric, electronic, and hydrogen-bond acceptor properties of the compounds.
ISSN:1424-8247
1424-8247
DOI:10.3390/ph16111621