Oliveira-Tintino Cícera Datiane de Morais, Santana Jorge Ederson Gonçalves, Alencar Gabriel Gonçalves, Siqueira Gustavo Miguel, Gonçalves Sheila Alves, Tintino Saulo Relison, Menezes Irwin Rose Alencar de, Rodrigues João Pedro Viana, Gonçalves Vanessa Barbosa Pinheiro, Nicolete Roberto, Ribeiro-Filho Jaime, da Silva Teresinha Gonçalves, Coutinho Henrique Douglas Melo
Department of Biological Chemistry, Regional University of Cariri (URCA), Crato 63105-010, CE, Brazil.
Department of Antibiotics, Federal University of Pernambuco (UFPE), Recife 50670-901, PE, Brazil.
Pharmaceutics. 2023 Sep 28;15(10):2400. doi: 10.3390/pharmaceutics15102400.
Valencene and nootkatone are aromatic sesquiterpenes with known biological activities, such as antimicrobial, antioxidant, anti-inflammatory, and antitumor. Given the evidence that encapsulation into nanosystems, such as liposomes, could improve the properties of several compounds, the present study aimed to evaluate the activity of these sesquiterpenes in their isolated state or in liposomal formulations against strains of carrying efflux pumps. The broth microdilution method evaluated the antibiotic-enhancing activity associated with antibiotics and ethidium bromide (EtBr). The minimum inhibitory concentration was assessed in strains of 1199B, IS-58, and RN4220, which carry the efflux proteins NorA, Tet(K), and MsrA. In tests with strain 1199B, valencene reduced the MIC of norfloxacin and EtBr by 50%, while the liposomal formulation of this compound did not show a significant effect. Regarding the strain IS-58, valencene, and its nanoformulation reduced norfloxacin MIC by 60.3% and 50%, respectively. In the non-liposomal form, the sesquiterpene reduced the MIC of EtBr by 90%. Against the RN4220 strain, valencene reduced the MIC of the antibiotic and EtBr by 99% and 93.7%, respectively. Nootkatone and its nanoformulation showed significant activity against the 1199B strain, reducing the EtBr MIC by 21.9%. Against the IS-58 strain, isolated nootkatone reduced the EtBr MIC by 20%. The results indicate that valencene and nootkatone potentiate the action of antibiotics and efflux inhibitors in strains carrying NorA, Tet(K), and MsrA proteins, which suggests that these sesquiterpenes act as efflux pump inhibitors in . Therefore, further studies are needed to assess the impact of incorporation into liposomes on the activity of these compounds in vivo.
瓦伦烯和诺卡酮是具有已知生物活性的芳香倍半萜，如抗菌、抗氧化、抗炎和抗肿瘤活性。鉴于有证据表明包封到纳米系统（如脂质体）中可以改善几种化合物的性质，本研究旨在评估这些倍半萜在其分离状态或脂质体制剂中对携带外排泵的菌株的活性。肉汤微量稀释法评估了与抗生素和溴化乙锭（EtBr）相关的抗生素增强活性。在携带外排蛋白NorA、Tet(K)和MsrA的1199B、IS-58和RN4220菌株中评估了最低抑菌浓度。在对1199B菌株的测试中，瓦伦烯使诺氟沙星和EtBr的MIC降低了50%，而该化合物的脂质体制剂未显示出显著效果。对于IS-58菌株，瓦伦烯及其纳米制剂分别使诺氟沙星MIC降低了60.3%和50%。在非脂质体形式下，该倍半萜使EtBr的MIC降低了90%。针对RN4220菌株，瓦伦烯使抗生素和EtBr的MIC分别降低了99%和93.7%。诺卡酮及其纳米制剂对1199B菌株显示出显著活性，使EtBr的MIC降低了21.9%。针对IS-58菌株，分离的诺卡酮使EtBr的MIC降低了20%。结果表明，瓦伦烯和诺卡酮增强了携带NorA、Tet(K)和MsrA蛋白的菌株中抗生素和外排抑制剂的作用，这表明这些倍半萜在[具体菌种未明确写出]中作为外排泵抑制剂起作用。因此，需要进一步研究来评估包封到脂质体中对这些化合物体内活性的影响。
