Repurposing FDA-approved sulphonamide carbonic anhydrase inhibitors for treatment of Neisseria gonorrhoeae.
Repurposing FDA-approved sulphonamide carbonic anhydrase inhibitors for treatment of Neisseria gonorrhoeae.
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DOI：
10.1080/14756366.2021.1991336
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发表时间：
2022-12
影响因子：
5.6
通讯作者：
Flaherty DP
中科院分区：
文献类型：
--
作者：
Abutaleb NS;Elhassanny AEM;Nocentini A;Hewitt CS;Elkashif A;Cooper BR;Supuran CT;Seleem MN;Flaherty DP
由于对批准的抗生素产生耐药性的日益普遍，淋病奈瑟菌是一种高度优先关注的病原体。在这里，我们报告了乙氧唑胺的抗淋球菌活性，乙氧唑胺是FDA批准的人碳酸酐酶抑制剂。乙氧唑胺对一组淋病奈瑟菌的最低抑菌浓度为0.125 微克/毫升，是乙酰唑胺的16倍，但两种分子在体外对淋球菌碳酸酐酶的效力几乎相同。乙酰唑胺对NgCA的抑制常数为74 nM，而乙氧唑胺的抑制常数为94 nM。因此，与乙酰唑胺相比，乙氧唑胺的抗淋球菌效力的增强归因于其对淋球菌的渗透性增加。这两种药物对淋病奈瑟菌均有抑菌活性，抗生素后作用时间长达10 小时，对两种药物均未观察到耐药性。综上所述，这些结果表明，乙酰唑胺和乙氧唑胺值得进一步研究，以转化为有效的抗N。淋病病原体。
Neisseria gonorrhoeae is a high-priority pathogen of concern due to the growing prevalence of resistance development against approved antibiotics. Herein, we report the anti-gonococcal activity of ethoxzolamide, the FDA-approved human carbonic anhydrase inhibitor. Ethoxzolamide displayed an MIC50, against a panel of N. gonorrhoeae isolates, of 0.125 µg/mL, 16-fold more potent than acetazolamide, although both molecules exhibited almost similar potency against the gonococcal carbonic anhydrase enzyme (NgCA) in vitro. Acetazolamide displayed an inhibition constant (Ki) versus NgCA of 74 nM, while Ethoxzolamide’s Ki was estimated to 94 nM. Therefore, the increased anti-gonococcal potency of ethoxzolamide was attributed to its increased permeability in N. gonorrhoeae as compared to that of acetazolamide. Both drugs demonstrated bacteriostatic activity against N. gonorrhoeae, exhibited post-antibiotic effects up to 10 hours, and resistance was not observed against both. Taken together, these results indicate that acetazolamide and ethoxzolamide warrant further investigation for translation into effective anti-N. gonorrhoeae agents.
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影响因子：
2.7
作者：
Abutaleb NS;Elhassanny AEM;Flaherty DP;Seleem MN
通讯作者：
Seleem MN
影响因子：
4
作者：
Davis, Tony D.;Gerry, Christopher J.;Tan, Derek S.
通讯作者：
Tan, Derek S.
影响因子：
4.9
作者：
Binet, Rachel;Maurelli, Anthony T.
通讯作者：
Maurelli, Anthony T.
影响因子：
6.7
作者：
Elsebaei, Mohamed M.;Abutaleb, Nader S.;Mayhoub, Abdelrahman S.
通讯作者：
Mayhoub, Abdelrahman S.
影响因子：
5.2
作者：
Camara, Jordi;Serra, Judit;Ardanuy, Carmen
通讯作者：
Ardanuy, Carmen