用生化、分子和形态学手段对丁香酚衍生物的体外和体内杀虫活性进行评价。

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Accounts of Chemical Research Pub Date : 2022-07-01 eCollection Date: 2022-01-01 DOI:10.1590/1678-9199-JVATITD-2021-0108
Isabella Maria Monteiro de Souza, Romulo Dias Novaes, Reggiani Vilela Gonçalves, Felipe Leonardo Bley Fialho, Diogo Teixeira Carvalho, Thiago Belarmino de Souza, Danielle Ferreira Dias, Stefânia Neiva Lavorato, Raquel Lopes Martins Souza, Marcos José Marques, Aline Pereira Castro
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引用次数: 2

摘要

背景:丁香酚具有抗菌和抗寄生虫活性,表明它可能被评估为治疗吡喹酮耐药血吸虫的一种选择。方法:采用荧光显微镜和扫描电镜分别检测3种丁香酚衍生物FB1、FB4和FB9对曼氏血吸虫成虫的体外活性,分析其对排泄系统和被膜损伤的影响。使用维拉帕米(一种钙通道拮抗剂)和瓦巴因(一种Na+/K+- atp酶泵抑制剂)的生化试验来表征丁香酚衍生物与钙通道和Na+/K+- atp酶的相互作用,而硅分析确定了潜在的Na+/K+- atp酶结合位点。结果:化合物的有效剂量ED50分别为0.324 mM (FB1)、0.167 mM (FB4)和0.340 mM (FB9)。此外,荧光和扫描电镜分析显示,ED50、ED90和ED100最低的FB4 (0.322 mM)对排泄系统和被膜的损伤最大(p < 0.05)。沃巴因加FB1(192小时vs 72小时)和FB9(192小时vs 168小时)可延迟成虫的死亡,但在有或没有沃巴因的情况下,对FB4的反应是相同的。此外,当所有丁香酚衍生物与维拉帕米联合使用时,没有注意到任何变化。此外,FB1和FB9抑制Na+/K+- atp酶活性,但FB4不表现出时间依赖性,可能作用于Na+/K+- atp酶以外的靶标。结论:与FB1和FB9相比,丁香酚衍生物(主要为FB4)对曼氏弓形虫成虫被膜的作用更有效。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

<i>In vitro</i> and <i>in silico</i> evaluation of the schistosomicidal activity of eugenol derivatives using biochemical, molecular, and morphological tools.

<i>In vitro</i> and <i>in silico</i> evaluation of the schistosomicidal activity of eugenol derivatives using biochemical, molecular, and morphological tools.

<i>In vitro</i> and <i>in silico</i> evaluation of the schistosomicidal activity of eugenol derivatives using biochemical, molecular, and morphological tools.

In vitro and in silico evaluation of the schistosomicidal activity of eugenol derivatives using biochemical, molecular, and morphological tools.

Background: Eugenol shows both antibacterial and antiparasitic activities, suggesting that it might be evaluated as an option for the treatment of praziquantel-resistant schistosome.

Methods: The in vitro activities of three eugenol derivatives (FB1, FB4 and FB9) on adult worms from Schistosoma mansoni were examined by fluorescence and scanning electron microscopy to analyze effects on the excretory system and integument damage, respectively. Biochemical tests with verapamil (a calcium channel antagonist) and ouabain (a Na+/K+-ATPase pump inhibitor) were used to characterize eugenol derivative interactions with calcium channels and the Na+/K+-ATPase, while in silico analysis identified potential Na+/K+-ATPase binding sites.

Results: The compounds showed effective doses (ED50) of 0.324 mM (FB1), 0.167 mM (FB4), and 0.340 mM (FB9). In addition, FB4 (0.322 mM), which showed the lowest ED50, ED90 and ED100 (p < 0.05), caused the most damage to the excretory system and integument, according to both fluorescence and scanning electron microscopy analysis. The death of adult worms was delayed by ouabain treatment plus FB1 (192 versus 72 hours) and FB9 (192 versus 168 hours), but the response to FB4 was the same in the presence or absence of ouabain. Besides, no changes were noted when all of the eugenol derivatives were combined with verapamil. Moreover, FB1 and FB9 inhibited Na+/K+-ATPase activity according to in silico analysis but FB4 did not show a time-dependent relationship and may act on targets other than the parasite Na+/K+-ATPase.

Conclusion: Eugenol derivatives, mainly FB4 when compared to FB1 and FB9, seem to act more effectively on the integument of adult S. mansoni worms.

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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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