Alternative approaches utilizing click chemistry to develop next-generation analogs of solithromycin.
Alternative approaches utilizing click chemistry to develop next-generation analogs of solithromycin.
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DOI：
10.1016/j.ejmech.2022.114213
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发表时间：
2022-04-05
影响因子：
6.7
通讯作者：
Andrade, Rodrigo B. B.
中科院分区：
文献类型：
--
作者：
Daher, Samer S.;Lee, Miseon;Jin, Xiao;Teijaro, Christiana N. N.;Barnett, Pamela R. R.;Freundlich, Joel S. S.;Andrade, Rodrigo B. B.
细菌耐药性的显著上升迫切需要新的抗菌药物，这些药物属于新的药物类别，理想情况下具有新的作用机制。与泰利霉素和其他大环内酯类抗生素相比，茄红霉素对链球菌和其他引起社区获得性肺炎病原体的细菌具有更好的生物活性，鼓励我们广泛探索这类抗生素。因此，我们介绍了一系列新的茄红霉素类似物的设计和合成。在N-11侧链和地塞米松基序的构效关系研究中采用了三种主要策略，这两种基序都是以细菌核糖体为分子靶标建立强相互作用的主要元件。采用最小抑菌浓度试验评价不同类似物对茄红霉素的体外药效。两个类似物对耐药菌株显示出比Soli红霉素更好的活性，这一点可以在进一步的临床前研究中进行评估。
The marked rise in bacterial drug resistance has created an urgent need for novel antibacterials belonging to new drug classes and ideally possessing new mechanisms of action. The superior biological activity of solithromycin against streptococci and other bacteria causative of community-acquired pneumonia pathogens, compared to telithromycin and other macrolides encouraged us to extensively explore this class of antibiotics. We, thus, present the design and synthesis of a novel series of solithromycin analogs. Three main strategies were pursued in structure-activity relationship studies covering the N-11 side chain and the desosamine motif, which are both chief elements for establishing strong interactions with the bacterial ribosome as the molecular target. Minimal inhibitory concentration assays were determined to assess the in vitro potency of the various analogs in relation to solithromycin. Two analogs exhibited improved activity compared to solithromycin against resistant strains, which can be assessed in further pre-clinical studies.
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DOI：
10.1038/ja.2016.137
发表时间：
2017-05
期刊：
The Journal of antibiotics
影响因子：
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影响因子：
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作者：
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