Benzodioxane-Benzamides as FtsZ Inhibitors: Effects of Linker's Functionalization on Gram-Positive Antimicrobial Activity.
Benzodioxane-Benzamides as FtsZ Inhibitors: Effects of Linker's Functionalization on Gram-Positive Antimicrobial Activity.
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DOI：
10.3390/antibiotics12121712
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发表时间：
2023-12-08
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影响因子：
--
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FtsZ是一种重要的细菌蛋白，作为一种新的和有前途的抗菌剂靶标进行了大量研究。FtsZ在细菌和分枝杆菌中是高度保守的，它对细胞分裂过程的正确结果至关重要，因为它负责将亲本细菌细胞分裂成两个子细胞。近年来，苯并二氧杂环己烷-苯甲酰胺类已经成为非常有前途的并且能够靶向革兰氏阳性和革兰氏阴性FtsZ。在这项研究中，我们探讨了在两个主要部分之间的烯键式接头上包括取代基对抗菌活性和药代动力学性质的影响。这种取代，反过来，导致产生的第二个立体中心，与邻位和苏型异构体分离，表征和评价。通过这项工作，我们发现了羟基如何轻微地影响抗微生物活性，同时作为开发和开发前药、探针和进一步衍生物的重要锚。
FtsZ is an essential bacterial protein abundantly studied as a novel and promising target for antimicrobials. FtsZ is highly conserved among bacteria and mycobacteria, and it is crucial for the correct outcome of the cell division process, as it is responsible for the division of the parent bacterial cell into two daughter cells. In recent years, the benzodioxane–benzamide class has emerged as very promising and capable of targeting both Gram-positive and Gram-negative FtsZs. In this study, we explored the effect of including a substituent on the ethylenic linker between the two main moieties on the antimicrobial activity and pharmacokinetic properties. This substitution, in turn, led to the generation of a second stereogenic center, with both erythro and threo isomers isolated, characterized, and evaluated. With this work, we discovered how the hydroxy group slightly affects the antimicrobial activity, while being an important anchor for the exploitation and development of prodrugs, probes, and further derivatives.
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DOI：
10.1038/nrmicro.2016.26
发表时间：
2016-04
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
Haeusser DP;Margolin W
通讯作者：
Margolin W
影响因子：
3
作者：
Sherman, W;Beard, HS;Farid, R
通讯作者：
Farid, R
影响因子：
3.5
作者：
Bolchi, C;Catalano, P;Valoti, E
通讯作者：
Valoti, E
影响因子：
56.9
作者：
Haydon, David J.;Stokes, Neil R.;Czaplewski, Lloyd G.
通讯作者：
Czaplewski, Lloyd G.
DOI：
10.1016/s0140-6736(21)02724-0
发表时间：
2022-02-12
期刊：
Lancet (London, England)
影响因子：
--
作者：
Antimicrobial Resistance Collaborators
通讯作者：
Antimicrobial Resistance Collaborators