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对溴化和氯化吡嗪基查尔酮的抗葡萄球菌和抗肠球菌作用的全面洞察。

Comprehensive insight into anti-staphylococcal and anti-enterococcal action of brominated and chlorinated pyrazine-based chalcones.

作者信息

Konečná Klára, Diepoltová Adéla, Holmanová Pavlína, Jand'ourek Ondřej, Vejsová Marcela, Voxová Barbora, Bárta Pavel, Maixnerová Jana, Trejtnar František, Kučerová-Chlupáčová Marta

机构信息

Department of Biological and Medical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, Hradec Králové, Czechia.

Department of Biophysics and Physical Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, Hradec Králové, Czechia.

出版信息

Front Microbiol. 2022 Aug 17;13:912467. doi: 10.3389/fmicb.2022.912467. eCollection 2022.

Abstract

The greatest threat and medicinal impact within gram-positive pathogens are posed by two bacterial genera, and . Chalcones have a wide range of biological activities and are recognized as effective templates in medicinal chemistry. This study provides comprehensive insight into the anti-staphylococcal and anti-enterococcal activities of two recently published brominated and chlorinated pyrazine-based chalcones, CH-0y and CH-0w. Their effects against 4 reference and 12 staphylococcal and enterococcal clinical isolates were evaluated. Bactericidal action, the activity in combination with selected conventional antibiotics, the study of post-antimicrobial effect (PAE, PAE/SME), and and toxicity, were included. In CH-0y, anti-staphylococcal activity ranging from MIC = 15.625 to 62.5 μM, and activity against from 31.25 to 62.5 μM was determined. In CH-0w, anti-staphylococcal activity ranging from 31.25 to 125 μM, and activity against and (62.5 μM) was revealed. Both CH-0y and CH-0w showed bactericidal action, beneficial impact on bacterial growth delay within PAE and PAE/SME studies, and non/low toxicity . Compared to CH-0w, CH-0y seems to have higher anti-staphylococcal and less toxic potential. In conclusion, chalcones CH-0y and CH-0w could be considered as structural pattern for future adjuvants to selected antibiotic drugs.

摘要

革兰氏阳性病原体中最大的威胁和医学影响由两个细菌属,即[具体细菌属1]和[具体细菌属2]造成。查耳酮具有广泛的生物活性,并且在药物化学中被认为是有效的模板。本研究全面深入地探究了两种最近发表的基于溴化和氯化吡嗪的查耳酮CH - 0y和CH - 0w的抗葡萄球菌和抗肠球菌活性。评估了它们对4株参考菌株以及12株葡萄球菌和肠球菌临床分离株的作用。研究内容包括杀菌作用、与选定的传统抗生素联合使用时的活性、抗菌后效应(PAE、PAE/SME)的研究以及[具体毒性指标1]和[具体毒性指标2]毒性。在CH - 0y中,测定的抗葡萄球菌活性范围为MIC = 15.625至62.5 μM,对[具体细菌名称]的活性范围为31.25至62.5 μM。在CH - 0w中,揭示的抗葡萄球菌活性范围为31.25至125 μM,对[具体细菌名称1]和[具体细菌名称2](62.5 μM)有活性。CH - 0y和CH - 0w均表现出杀菌作用,在PAE和PAE/SME研究中对细菌生长延迟有有益影响,并且具有非/低[具体毒性指标1]和[具体毒性指标2]毒性。与CH - 0w相比,CH - 0y似乎具有更高的抗葡萄球菌潜力且毒性更低。总之,查耳酮CH - 0y和CH - 0w可被视为未来某些抗生素药物佐剂的结构模式。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c94/9428509/4345f209a49c/fmicb-13-912467-g001.jpg

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