Antibacterial effect, efflux pump inhibitory (NorA, TetK and MepA) of Staphylococcus aureus and in silico prediction of α, β and δ-damascone compounds

• Published in: Arabian journal of chemistry Vol. 16; no. 2; p. 104482
• Main Authors: Rayane Correia de Oliveira, Maria, Gabriely de Lima Silva, Maria, Datiane de Morais Oliveira-Tintino, Cícera, Relison Tintino, Saulo, Esmeraldo Rocha, Janaina, Ernani Alves Magalhães, Francisco, Henrique Sousa da Costa, Roger, Torres Pessoa, Renata, Sousa Alcântara, Isabel, Oliveira Brito Pereira Bezerra Martins, Anita, Douglas Melo Coutinho, Henrique, Raposo, António, Carrascosa, Conrado, Raduan Jaber, José, Aquino Saraiva, Rogério, Rose Alencar de Menezes, Irwin
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01-02-2023; Elsevier
• Subjects: ADME; Antibacterial; Damascone; Efflux pump; Molecular docking; Antibacterial; Damascone; ADME; Efflux pump; Molecular docking
• ISSN: 1878-5352; 1878-5379
• DOI: 10.1016/j.arabjc.2022.104482

The present study aimed to evaluate the antibacterial effect and inhibitory capacity against NorA, TetK and MepA efflux pump of Staphylococcus aureus multiresistant by in vitro and in silico approach of α, β and δ-damascone compounds.
The compounds α, β and δ-damascone showed a clinically relevant effect against S. aureus ATCC 6538 standard strain. A modulating effect was also observed in association with antibiotics against MDR strains. Regarding the inhibition of the efflux pump, the compounds showed a modulating effect with antibiotics, against SA-1199, SA-1199B, SA IS-58 and K2068. Only δ-damascone demonstrated an efflux pump inhibitory effect. Regarding ADME properties, α, β and δ-damascone showed similar physicochemical properties with good pharmacokinetic characteristics, such as lipophilicity, oral bioavailability and low toxicity. In addition, they exhibited the binding energy and Ligand Efficiency (LE) −81.17 (5.4), −77.48(-5.4) and −64.55 (-5.1), which shows good interactions with the critical residues of the MepA receptor.
From the results it is concluded that the compounds α, β and δ-damascone do not have antibacterial activity, but show a modulating effect in association with antibiotics, as well as not showing direct activity on the efflux pump, but they do have a modulating effect with antibiotics and with EtBr (α and β-damascone).