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5,8-二羟基-1,4-萘醌的体外抗菌作用及灭活机制

In Vitro Antimicrobial Effects and Inactivation Mechanisms of 5,8-Dihydroxy-1,4-Napthoquinone.

作者信息

Topçu Seray, Şeker Mine Gül

机构信息

Department of Molecular Biology and Genetics, Gebze Technical University, Gebze 41 400, Kocaeli, Türkiye.

出版信息

Antibiotics (Basel). 2022 Nov 3;11(11):1537. doi: 10.3390/antibiotics11111537.

Abstract

Naphthoquinones are an important class of natural organic compounds that have antimicrobial effects. However, the mechanisms of their action remain to be elucidated. Therefore, the antimicrobial activity of the chemically synthesized naphthoquinone derivative, 5,8-dihydroxy-1,4-naphthoquinone, was investigated in this study against 10 different microorganisms. Its inhibitory activity was evident against Bacillus cereus, Proteus vulgaris, Salmonella enteritidis, Staphylococcus epidermidis, S. aureus, and Candida albicans, and its MIC50 values were determined to be 14, 10, 6, 2, 4, 1.2, and <0.6 µg/mL, respectively. Moreover, the crystal violet uptake, TTC dehydrogenase activity, protein/DNA leakage, and DNA damage of the compound in these microorganisms were also investigated to reveal the antimicrobial mechanisms. In addition, scanning electron microscopy was used to detect physiological damage to the cell membrane of S. epidermidis, S. aureus, and C. albicans, which was most severe in the crystal violet uptake assay. The overall results showed that 5,8-dihydroxy-1,4-naphthoquinone exhibited its effects on S. aureus, S. epidermidis, and C. albicans by various mechanisms, especially membrane damage and membrane integrity disruption. It also caused DNA leakage and damage along with respiratory chain disruption (78%) in C. albicans. Similarly, it caused varying degrees of reduction in the respiratory activity of S. aureus (47%), S. epidermidis (16%), B. cereus (12%), S. enteritidis (9%), and P. vulgaris (8%). Therefore, 5,8-dihydroxy-1,4-naphthoquinone proved to be a very effective antifungal and antibacterial agent and could be considered a new potential drug candidate, inspiring further discoveries in these microorganisms.

摘要

萘醌是一类具有抗菌作用的重要天然有机化合物。然而,其作用机制仍有待阐明。因此,本研究考察了化学合成的萘醌衍生物5,8 - 二羟基 - 1,4 - 萘醌对10种不同微生物的抗菌活性。它对蜡样芽孢杆菌、普通变形杆菌、肠炎沙门氏菌、表皮葡萄球菌、金黄色葡萄球菌和白色念珠菌具有明显的抑制活性,其MIC50值分别测定为14、10、6、2、4、1.2和<0.6 µg/mL。此外,还研究了该化合物在这些微生物中的结晶紫摄取、TTC脱氢酶活性、蛋白质/DNA泄漏及DNA损伤情况,以揭示其抗菌机制。另外,采用扫描电子显微镜检测了该化合物对表皮葡萄球菌、金黄色葡萄球菌和白色念珠菌细胞膜的生理损伤,在结晶紫摄取试验中这种损伤最为严重。总体结果表明,5,8 - 二羟基 - 1,4 - 萘醌通过多种机制对金黄色葡萄球菌、表皮葡萄球菌和白色念珠菌发挥作用,尤其是膜损伤和膜完整性破坏。它还导致白色念珠菌的DNA泄漏和损伤以及呼吸链破坏(78%)。同样,它使金黄色葡萄球菌(47%)、表皮葡萄球菌(16%)、蜡样芽孢杆菌(12%)、肠炎沙门氏菌(9%)和普通变形杆菌(8%)的呼吸活性出现不同程度降低。因此,5,8 - 二羟基 - 1,4 - 萘醌被证明是一种非常有效的抗真菌和抗菌剂,可被视为一种新的潜在药物候选物,有望在这些微生物研究中带来更多新发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c582/9687054/eff16cf82427/antibiotics-11-01537-g001.jpg

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