Araújo-Neto José B de, Oliveira-Tintino Cícera D de M, de Araújo Gildênia A, Alves Daniel S, Ribeiro Fernanda R, Brancaglion Guilherme A, Carvalho Diogo T, Lima Clara Mariana Gonçalves, Mohammed Ali Hani S H, Rather Irfan A, Wani Mohmmad Y, Emran Talha B, Coutinho Henrique D M, Balbino Valdir de Q, Tintino Saulo R
Postgraduate Program in Biological Sciences, Biosciences Center, Federal University of Pernambuco, Recife 50740-570, PE, Brazil.
Laboratory of Microbiology and Molecular Biology, Department of Biological Chemistry, Regional University of Cariri, Crato 63105-000, CE, Brazil.
Antibiotics (Basel). 2023 Dec 15;12(12):1739. doi: 10.3390/antibiotics12121739.
Coumarins are compounds with scientifically proven antibacterial properties, and modifications to the chemical structure are known to improve their effects. This information is even more relevant with the unbridled advances of antibiotic resistance, where and its efflux pumps play a prominent role. The study's objective was to evaluate the potential of synthetic coumarins with different substitutions in the C-3 position as possible inhibitors of the NorA and MepA efflux pumps of . For this evaluation, the following steps took place: (i) the determination of the minimum inhibitory concentration (MIC); (ii) the association of coumarins with fluoroquinolones and ethidium bromide (EtBr); (iii) the assessment of the effect on EtBr fluorescence emission; (iv) molecular docking; and (v) an analysis of the effect on membrane permeability. Coumarins reduced the MICs of fluoroquinolones and EtBr between 50% and 87.5%. Coumarin C1 increased EtBr fluorescence emission between 20 and 40% by reinforcing the evidence of efflux inhibition. The molecular docking results demonstrated that coumarins have an affinity with efflux pumps and establish mainly hydrogen bonds and hydrophobic interactions. Furthermore, C1 did not change the permeability of the membrane. Therefore, we conclude that these 3-substituted coumarins act as inhibitors of the NorA and MepA efflux pumps of .
香豆素是具有经科学验证的抗菌特性的化合物，已知对其化学结构进行修饰可增强其效果。随着抗生素耐药性的肆意发展，这一信息变得愈发重要，其中[具体细菌名称]及其外排泵起着显著作用。该研究的目的是评估在C-3位具有不同取代基的合成香豆素作为[具体细菌名称]的NorA和MepA外排泵潜在抑制剂的可能性。为进行此评估，采取了以下步骤：（i）测定最低抑菌浓度（MIC）；（ii）将香豆素与氟喹诺酮类和溴化乙锭（EtBr）结合；（iii）评估对EtBr荧光发射的影响；（iv）分子对接；以及（v）分析对膜通透性的影响。香豆素使氟喹诺酮类和EtBr的MIC降低了50%至87.5%。香豆素C1通过加强外排抑制的证据使EtBr荧光发射增加了20%至40%。分子对接结果表明，香豆素与外排泵具有亲和力，主要形成氢键和疏水相互作用。此外，C1并未改变膜的通透性。因此，我们得出结论，这些3-取代香豆素可作为[具体细菌名称]的NorA和MepA外排泵的抑制剂。
