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N-苄基-N-苯基喹唑啉-2,4-二胺化合物对金黄色葡萄球菌和表皮葡萄球菌具有抗菌和抗生物膜作用。

N -benzyl-N -phenylquinazoline-2,4-diamine compound presents antibacterial and antibiofilm effect against Staphylococcus aureus and Staphylococcus epidermidis.

机构信息

Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.

Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.

出版信息

Chem Biol Drug Des. 2020 Dec;96(6):1372-1379. doi: 10.1111/cbdd.13745. Epub 2020 Aug 4.

DOI:10.1111/cbdd.13745
PMID:32542979
Abstract

Staphylococcus aureus and Staphylococcus epidermidis are the main agents involved with implant-related infections. Their ability to adhere to medical devices with subsequent biofilm formation is crucial to the development of these infections. Herein, we described the antibacterial and antibiofilm activities of a quinazoline-based compound, N -benzyl-N -phenylquinazoline-2,4-diamine, against both biofilm-forming pathogens. The minimum inhibitory concentrations (MIC) were determined as 25 µM for S. aureus and 15 µM for S. epidermidis. At sub-MIC concentrations (20 µM for S. aureus and 10 µM for S. epidermidis), the compound was able to inhibit biofilm formation without interfere with bacterial growth, confirmed by scanning electron microscopy. Moreover, surfaces coated with the quinazoline-based compound were able to prevent bacterial adherence. In addition, this compound presented no toxicity to human red blood cells at highest MIC 25 µM and in vivo toxicity assay using Galleria mellonella larvae resulted in 82% survival with a high dose of 500 mg/kg body weight. These features evidence quinazoline-based compound as interesting entities to promising applications in biomedical fields, such as antimicrobial and in anti-infective approaches.

摘要

金黄色葡萄球菌和表皮葡萄球菌是与植入物相关感染有关的主要病原体。它们能够附着在医疗设备上并随后形成生物膜,这对这些感染的发展至关重要。在此,我们描述了一种基于喹唑啉的化合物 N -苄基-N -苯基喹唑啉-2,4-二胺对两种形成生物膜的病原体的抗菌和抗生物膜活性。最小抑菌浓度(MIC)分别为金黄色葡萄球菌 25 μM 和表皮葡萄球菌 15 μM。在亚 MIC 浓度(金黄色葡萄球菌 20 μM,表皮葡萄球菌 10 μM)下,该化合物能够在不影响细菌生长的情况下抑制生物膜形成,这通过扫描电子显微镜得到了证实。此外,用基于喹唑啉的化合物涂覆的表面能够防止细菌附着。此外,该化合物在最高 MIC 25 μM 时对人红细胞没有毒性,并且在使用大蜡螟幼虫的体内毒性试验中,高剂量 500 mg/kg 体重时存活率为 82%。这些特征表明基于喹唑啉的化合物作为有前途的抗菌和抗感染方法在生物医学领域的应用的有前途的实体。

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