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

Autor: Andrades-Lagos J; Facultad de Medicina y Ciencia, Universidad San Sebastián, Santiago 7510157, Chile.; Drug Development Laboratory, Faculty of Chemical and Pharmaceutical, Sciences, Universidad de Chile, Santiago 8380492, Chile., Campanini-Salinas J; Drug Development Laboratory, Faculty of Chemical and Pharmaceutical, Sciences, Universidad de Chile, Santiago 8380492, Chile.; Facultad de Medicina y Ciencia, Universidad San Sebastián, Puerto Montt 5501842, Chile., Sabadini G; Instituto de Química y Bioquímica, Facultad de Ciencias, Universidad de Valparaíso, Av. Gran Bretaña 1111, Valparaíso 2360102, Chile.; Centro de Investigación Farmacopea Chilena, Facultad de Farmacia, Universidad de Valparaíso, Av. Gran Bretaña 1093, Valparaíso 2360102, Chile., Andrade V; Laboratory of Neuroscience and Functional Medicine, International Center for Biomedicine, Faculty of Sciences, University of Chile, Santiago 7800003, Chile.; Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Medical Faculty, University of Cologne, 50923 Köln, Germany.; Department of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, 53127 Bonn, Germany., Mella J; Instituto de Química y Bioquímica, Facultad de Ciencias, Universidad de Valparaíso, Av. Gran Bretaña 1111, Valparaíso 2360102, Chile.; Centro de Investigación Farmacopea Chilena, Facultad de Farmacia, Universidad de Valparaíso, Av. Gran Bretaña 1093, Valparaíso 2360102, Chile., Vásquez-Velásquez D; Drug Development Laboratory, Faculty of Chemical and Pharmaceutical, Sciences, Universidad de Chile, Santiago 8380492, Chile.
Jazyk: angličtina
Zdroj: Pharmaceuticals (Basel, Switzerland) [Pharmaceuticals (Basel)] 2023 Nov 17; Vol. 16 (11). Date of Electronic Publication: 2023 Nov 17.
DOI: 10.3390/ph16111621
Abstrakt: 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 (r 2 = 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.
Databáze: MEDLINE
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