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In vitro and in silico antibacterial evaluation of coumarin derivatives against MDR strains of Staphylococcus aureus and Escherichia coli

2023; Elsevier BV; Volume: 177; Linguagem: Inglês

10.1016/j.micpath.2023.106058

1096-1208

Ana Luíza A.R. Martin, Irwin Rose Alencar de Menezes, Amanda Karine de Sousa, Pablo Antônio Maia de Farias, Francisco Antônio Vieira dos Santos, Thiago Sampaio de Freitas, Fernando Gomes Figueredo, Jaime Ribeiro‐Filho, Diogo Teixeira Carvalho, Henrique Douglas Melo Coutinho, M.M.F. Fonteles,

Analytical Chemistry and Chromatography

The increase in antibiotic resistance rates has attracted the interest of researchers for antibacterial compounds capable of potentiating the activity of conventional antibiotics. Coumarin derivatives have been reported to develop effective antibacterials with possible new mechanisms of action for treating infectious diseases caused by bacteria with a profile of drug resistance. In this context, the aim of the present study we have now prepared one variety of new synthetic coumarins evaluating the pharmacokinetic and chemical similarity in silico, their antimicrobial activity against Staphylococcus aureus (ATCC 25923) and Escherichia coli (ATCC 25922), and potential for the modulation of antibiotic resistance against Staphylococcus aureus (SA10) and Escherichia coli (EC06) clinical isolate bacteria by in vitro assay. The antibacterial activity and antibiotic-enhancing properties were evaluated by the broth microdilution method and pharmacokinetically characterized according to the Lipinsk rule of 5 and had their similarity analyzed in databases such as ChemBL and CAS SciFinder. The results demonstrated that only compound C13 showed significant antibacterial activity (MIC ≤256 μg/mL), and all other coumarins did not display relevant antibacterial activity (MIC ≥1024 μg/mL). However, they did modulate the antibiotics activities to norfloxacin and gentamicin, except, compound C11 to norfloxacin against Staphylococcus aureus (SA10). The in silico properties prediction and drug-likeness results demonstrated that all coumarins presented a good drug-likeness score with no violations and promising in silico pharmacokinetic profiles showing that they have the potential to be developed into an oral drug. The results indicate that the coumarin derivatives showed good in vitro antibacterial activity. These new coumarin derivatives also demonstrated the capacity to modulate antibiotic resistance with potential synergy action for current antimicrobials assayed, as antibiotic adjuvants, to reduce the emergence of antimicrobial resistance.