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咪唑噻唑衍生物对食脑变形虫显示出强效作用。

Imidazothiazole Derivatives Exhibited Potent Effects against Brain-Eating Amoebae.

作者信息

Siddiqui Ruqaiyyah, El-Gamal Mohammed I, Boghossian Anania, Saeed Balsam Qubais, Oh Chang-Hyun, Abdel-Maksoud Mohammed S, Alharbi Ahmad M, Alfahemi Hasan, Khan Naveed Ahmed

机构信息

College of Arts and Sciences, American University of Sharjah, Sharjah 26666, United Arab Emirates.

Department of Medical Biology, Faculty of Medicine, Istinye University, Istanbul 34010, Turkey.

出版信息

Antibiotics (Basel). 2022 Oct 30;11(11):1515. doi: 10.3390/antibiotics11111515.

Abstract

is a free-living, unicellular, opportunistic protist responsible for the fatal central nervous system infection, primary amoebic meningoencephalitis (PAM). Given the increase in temperatures due to global warming and climate change, it is estimated that the cases of PAM are on the rise. However, there is a current lack of awareness and effective drugs, meaning there is an urgent need to develop new therapeutic drugs. In this study, the target compounds were synthesized and tested for their anti-amoebic properties against Most compounds exhibited significant amoebicidal effects against ; for example, , , and reduced viability to 15.14%, 17.45% and 28.78%, respectively. Furthermore, the majority of the compounds showed reductions in amoeba-mediated host death. Of interest are the compounds , , and , as they were capable of reducing the amoeba-mediated host cell death to 52.3%, 51%, and 56.9% from 100%, respectively. Additionally, these compounds exhibit amoebicidal properties as well; they were found to decrease viability to 26.41%, 27.39%, and 24.13% from 100%, respectively. Moreover, the MIC values for , , and were determined to be 48.45 µM, 60.87 µM, and 50.96 µM, respectively. Additionally, the majority of compounds were found to exhibit limited cytotoxicity, except for , , , , , , , , , and , which exhibited negligible toxicity. It is anticipated that these compounds may be developed further as effective treatments against these devastating infections due to brain-eating amoebae.

摘要

是一种自由生活的单细胞机会性原生生物,可导致致命的中枢神经系统感染,即原发性阿米巴脑膜脑炎(PAM)。鉴于全球变暖和气候变化导致气温上升,据估计PAM病例正在增加。然而,目前人们对此缺乏认识且缺乏有效的药物,这意味着迫切需要开发新的治疗药物。在本研究中,合成了目标化合物并测试了它们对的抗阿米巴特性。大多数化合物对表现出显著的杀阿米巴作用;例如,、和分别将的活力降低至15.14%、17.45%和28.78%。此外,大多数化合物显示出可减少阿米巴介导的宿主死亡。有趣的是化合物、和,因为它们能够将阿米巴介导的宿主细胞死亡分别从100%降低至52.3%、51%和56.9%。此外,这些化合物也表现出杀阿米巴特性;发现它们分别将的活力从100%降低至26.41%、27.39%和24.13%。此外,、和的MIC值分别确定为48.45μM、60.87μM和50.96μM。此外,发现大多数化合物表现出有限的细胞毒性,除了、、、、、、、、和表现出可忽略不计的毒性。预计这些化合物可能会进一步开发成为针对这些由食脑阿米巴引起的毁灭性感染的有效治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d68d/9686523/cb5b9a1f3d1b/antibiotics-11-01515-g001.jpg

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