Lu Bin, Qiao Qi, Park Elizabeth R, Wang Yuxuan, Gilleran John A, Pan Matthew, Pilch Daniel S, Wu Xiang, Roberge Jacques Y, Fan Huizhou
Department of Parasitology, Central South University Xiangya Medical School, Changsha, Hunan 410013, China.
Department of Pharmacology, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, United States.
ACS Omega. 2023 Feb 8;8(7):6597-6607. doi: 10.1021/acsomega.2c06992. eCollection 2023 Feb 21.
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 and , these new antichlamydials are 2- to 5-fold more potent over the benzal acylhydrazone-based second-generation selective antichlamydial lead . Both acylpyrazoline-based SACs are well tolerated by , , , and as well as host cells. These third-generation selective antichlamydials merit further evaluation for therapeutic application.
衣原体是专性细胞内革兰氏阴性菌，是人和动物中广泛存在的病原体。目前使用广谱抗生素治疗衣原体感染。然而，广谱药物也会杀死有益细菌。最近，两代苯甲酰腙已被证明能选择性抑制衣原体，而对人类细胞和乳酸杆菌无毒，乳酸杆菌是育龄妇女生殖道中占主导地位的有益细菌。在此，我们报告了两种基于酰基吡唑啉的第三代选择性抗衣原体药物（SACs）的鉴定。这些新型抗衣原体药物对沙眼衣原体和生殖支原体的最低抑菌浓度（MIC）和最低杀菌浓度（MBC）为10-25μM，比基于苯甲酰腙的第二代选择性抗衣原体先导药物的效力高2至5倍。两种基于酰基吡唑啉的SACs对沙眼衣原体、生殖支原体、人宫颈癌细胞系HeLa、人胚胎肾细胞系HEK293以及宿主细胞的耐受性都很好。这些第三代选择性抗衣原体药物值得进一步评估其治疗应用价值。
