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Novel Azoles as Antiparasitic Remedies against Brain-Eating Amoebae

机译:新型偶氮唑类药物作为抗脑食性变形虫的抗寄生虫药物。

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摘要

and are opportunistic protozoan pathogens capable of producing infection of the central nervous system with more than 95% mortality rate. Previously, we have synthesized several compounds with antiamoebic properties; however, synthesis of compounds that are analogues of clinically used drugs is a highly desirable approach that can lead to effective drug development against these devastating infections. In this regard, compounds belonging to the azole class possess wide range of antimicrobial properties and used clinically. In this study, six novel benzimidazole, indazole, and tetrazole derivatives were synthesized and tested against brain-eating amoebae. These compounds were tested for their amoebicidal and static properties against and . Furthermore, the compounds were conjugated with silver nanoparticles and characterized. The synthetic heterocyclic compounds showed up to 72% and 65% amoebicidal activities against and respectively, while expressing up to 75% and 70% amoebistatic activities, respectively. Following conjugation with silver nanoparticles, amoebicidal activities of the drugs increased by up to 46 and 36% versus and Minimal effects were observed when the compounds were evaluated against human cells using cytotoxicity assays. In summary, azole compounds exhibited potent activity against and Moreover, conjugation of the azole compounds with silver nanoparticles further augmented the capabilities of the compounds against amoebae.
机译:和 是机会性原生动物病原体,能够引起中枢神经系统感染,死亡率超过95%。以前,我们已经合成了几种具有抗氧特性的化合物。然而,合成作为临床使用药物的类似物的化合物是非常需要的方法,其可以导致针对这些破坏性感染的有效药物开发。在这方面,属于唑类的化合物具有广泛的抗菌性能,并在临床上使用。在这项研究中,合成了六种新颖的苯并咪唑,吲唑和四唑衍生物,并测试了其对食脑变形虫的抵抗力。对这些化合物的抗杀虫和静态性能进行了测试。此外,化合物与银纳米颗粒共轭并表征。合成的杂环化合物分别针对和分别显示出高达72%和65%的杀菌活性,同时分别表达了高达75%和70%的阿米巴生活性。与银纳米颗粒结合后,该药物的杀螨活性增加了46%和36%,而使用细胞毒性测定法评估了这些化合物对人细胞的作用则最小。总而言之,唑化合物显示出对甲氧磷的有效活性。此外,唑化合物与银纳米粒子的结合进一步增强了该化合物对抗变形虫的能力。

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