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咔唑、氨基胍和二胺类抗感染药对……的活性

Activity of Carbazole, Aminoguanidine and Diamine Anti-infectives against .

作者信息

Singh Davinder, Sleda Melissa A, Pandey Akanksha, Malwal Satish R, Chen Yiyuan, Zhou Ruijie, Adewole Feyisola, Sadowska Katie, Onajole Oluseye K, Moreno Silvia N J, Oldfield Eric

机构信息

Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.

Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA, 30602, USA.

出版信息

bioRxiv. 2025 Feb 16:2025.02.15.638445. doi: 10.1101/2025.02.15.638445.

Abstract

We report the observation that carbazole anti-infectives developed as antibacterial and antifungal drug leads have activity against the tachyzoite-stage growth of the Apicomplexan parasite with IC values as low as 2 μM. We show that a phenylthiazole aminoguanidine with antibacterial as well as antifungal activity inhibits growth with an IC value of 2.1 μM. We also tested a series of 18 analogs of the diamine SQ109, a tuberculosis drug candidate which likewise has both antibacterial and antifungal activity, finding activity as low as 2.3 μM. We tested all compounds for their activity in collapsing the ΔpH component of the promotive force, the results indicating that all compounds acted, at least in part, as protonophore uncouplers. Finally, we also investigated the correlation between the activity of all compounds against the yeast and the bacterium , finding significant correlations between the collapse of the proton motive force and anti-fungal/antibacterial activity.

摘要

我们报告了以下观察结果

作为抗菌和抗真菌药物先导物开发的咔唑类抗感染剂对顶复门寄生虫的速殖子阶段生长具有活性,其IC值低至2μM。我们表明,一种具有抗菌和抗真菌活性的苯基噻唑氨基胍以2.1μM的IC值抑制生长。我们还测试了一系列18种二胺SQ109(一种同样具有抗菌和抗真菌活性的结核病候选药物)的类似物,发现其活性低至2.3μM。我们测试了所有化合物在破坏促进力的ΔpH成分方面的活性,结果表明所有化合物至少部分地作为质子载体解偶联剂起作用。最后,我们还研究了所有化合物对酵母和细菌的活性之间的相关性,发现质子动力势的破坏与抗真菌/抗菌活性之间存在显著相关性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0c2/11844542/817fbf205763/nihpp-2025.02.15.638445v1-f0001.jpg

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