Acylpyrazoline-Based Third-Generation Selective Antichlamydial Compounds with Enhanced Potency.
Acylpyrazoline-Based Third-Generation Selective Antichlamydial Compounds with Enhanced Potency.
复制标题
DOI：
10.1021/acsomega.2c06992
复制
发表时间：
2023-02-21
期刊：
影响因子：
4.1
通讯作者：
Fan, Huizhou
中科院分区：
文献类型：
--
作者：
Lu, Bin;Qiao, Qi;Park, Elizabeth R.;Wang, Yuxuan;Gilleran, John A.;Pan, Matthew;Pilch, Daniel S.;Wu, Xiang;Roberge, Jacques Y.;Fan, Huizhou
衣原体是专性细胞内革兰氏阴性细菌，是人类和动物中广泛存在的病原体。广谱抗生素目前用于治疗衣原体感染。然而，广谱药物也会杀死有益细菌。最近，两代苄叉酰腙已显示出选择性抑制衣原体，而对人类细胞和乳酸杆菌没有毒性，这是育龄妇女阴道中占主导地位的有益细菌。在这里，我们报告了两个酰基吡唑啉为基础的第三代选择性抗衣原体（SAC）的鉴定。这些新的抗衣原体药物对沙眼衣原体和鼠衣原体的最低抑菌浓度（MIC）和最低杀菌浓度（MBC）为10-25 μM，其效力是基于苄叉酰腙的第二代选择性抗衣原体先导物SF 3的2- 5倍。两种酰基吡唑啉类SAC均被乳杆菌属、大肠杆菌、克雷伯氏菌属和沙门氏菌属以及宿主细胞良好耐受。这些第三代选择性抗衣原体药物值得进一步评价治疗应用。
Chlamydiae are obligate intracellular Gram-negative bacteria and widespread pathogens in humans and animals. Broad-spectrum antibiotics are currently used to treat chlamydial infections. However, broad-spectrum drugs also kill beneficial bacteria. Recently, two generations of benzal acylhydrazones have been shown to selectively inhibit chlamydiae without toxicity to human cells and lactobacilli, which are dominating, beneficial bacteria in the vagina of reproductive-age women. Here, we report the identification of two acylpyrazoline-based third-generation selective antichlamydials (SACs). With minimal inhibitory concentrations (MIC) and minimal bactericidal concentrations (MBC) of 10–25 μM against Chlamydia trachomatis and Chlamydia muridarum, these new antichlamydials are 2- to 5-fold more potent over the benzal acylhydrazone-based second-generation selective antichlamydial lead SF3. Both acylpyrazoline-based SACs are well tolerated by Lactobacillus, Escherichia coli, Klebsiella, and Salmonella as well as host cells. These third-generation selective antichlamydials merit further evaluation for therapeutic application.
登录
查看更多内容
DOI：
10.1099/mic.0.049668-0
发表时间：
2011-09
期刊：
Microbiology (Reading, England)
影响因子：
--
作者：
Bao X;Pachikara ND;Oey CB;Balakrishnan A;Westblade LF;Tan M;Chase T;Nickels BE;Fan H
通讯作者：
Fan H
影响因子：
5.2
作者：
Parolin, Carola;Frisco, Giulia;Calonghi, Natalia
通讯作者：
Calonghi, Natalia
影响因子：
6.1
作者：
Bonacker, D;Stoiber, T;Bolt, HM
通讯作者：
Bolt, HM
影响因子：
4.9
作者：
Lenart, J;Andersen, AA;Rockey, DD
通讯作者：
Rockey, DD
影响因子：
6.1
作者：
Million, M.;Thuny, F.;Angelakis, E.;Casalta, J-P;Giorgi, R.;Habib, G.;Raoult, D.
通讯作者：
Raoult, D.