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卤化苯并嗪和喹啉类药物以及 NH125 类似物对兽医支原体的疗效数据。

Efficacy data of halogenated phenazine and quinoline agents and an NH125 analogue to veterinary mycoplasmas.

机构信息

Department of Environmental and Global Health, College of Public Health and Health Professions, University of Florida, Gainesville, Florida, USA.

Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, Gainesville, Florida, USA.

出版信息

BMC Vet Res. 2020 Apr 6;16(1):107. doi: 10.1186/s12917-020-02324-4.

Abstract

BACKGROUND

Mycoplasmas primarily cause respiratory or urogenital tract infections impacting avian, bovine, canine, caprine, murine, and reptilian hosts. In animal husbandry, mycoplasmas cause reduced feed-conversion, decreased egg production, arthritis, hypogalactia or agalactia, increased condemnations, culling, and mortality in some cases. Antibiotics reduce transmission and mitigate clinical signs; however, concerning levels of antibiotic resistance in Mycoplasma gallisepticum and M. capricolum isolates exist. To address these issues, we evaluated the minimum inhibitory concentrations (MICs) of halogenated phenazine and quinoline compounds, an N-arylated NH125 analogue, and triclosan against six representative veterinary mycoplasmas via microbroth or agar dilution methods. Thereafter, we evaluated the minimum bactericidal concentration (MBC) of efficacious drugs.

RESULTS

We identified several compounds with MICs ≤25 μM against M. pulmonis (n = 5), M. capricolum (n = 4), M. gallisepticum (n = 3), M. alligatoris (n = 3), M. agassizii (n = 2), and M. canis (n = 1). An N-arylated NH125 analogue, compound 21, served as the most efficacious, having a MIC ≤25 μM against all mycoplasmas tested, followed by two quinolines, nitroxoline (compound 12) and compound 20, which were effective against four and three mycoplasma type strains, respectively. Nitroxoline exhibited bactericidal activity among all susceptible mycoplasmas, and compound 21 exhibited bactericidal activity when the MBC was able to be determined.

CONCLUSIONS

These findings highlight a number of promising agents from novel drug classes with potential applications to treat veterinary mycoplasma infections and present the opportunity to evaluate preliminary pharmacokinetic indices using M. pulmonis in rodents as an animal model of human infection.

摘要

背景

支原体主要引起呼吸道或泌尿生殖道感染,影响禽类、牛类、犬类、山羊类、鼠类和爬行类宿主。在畜牧业中,支原体导致饲料转化率降低、产蛋量减少、关节炎、低乳或无乳、增加淘汰率、淘汰和死亡率等问题。抗生素可以减少传播并减轻临床症状;然而,支原体分离株中已经存在支原体感染和支原体感染的抗生素耐药性问题。为了解决这些问题,我们通过微量肉汤或琼脂稀释法评估了卤代吩嗪和喹啉化合物、N-芳基 NH125 类似物和三氯生对六种代表性兽医支原体的最小抑菌浓度(MIC),然后评估了有效药物的最小杀菌浓度(MBC)。

结果

我们发现了几种 MIC 值≤25μM 的化合物,对 M. pulmonis(n=5)、M. capricolum(n=4)、M. gallisepticum(n=3)、M. alligatoris(n=3)、M. agassizii(n=2)和 M. canis(n=1)有效。一种 N-芳基 NH125 类似物,化合物 21,是最有效的,对所有测试的支原体的 MIC 值都≤25μM,其次是两种喹啉,硝噁啉(化合物 12)和化合物 20,分别对四种和三种支原体标准株有效。硝噁啉对所有敏感支原体均具有杀菌活性,而化合物 21 在能够确定 MBC 时也具有杀菌活性。

结论

这些发现突出了一些有前途的新型药物类别中的化合物,它们可能应用于治疗兽医支原体感染,并提供了使用啮齿动物作为人类感染动物模型评估初步药代动力学指数的机会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4aa/7137434/8062e38cf5b3/12917_2020_2324_Fig1_HTML.jpg

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