摘要
背景:由锥虫属(Trypanosoma)和疟原虫(Plasmodium)的原生动物寄生虫引起的寄生虫病在热带和亚热带地区引起一些致命和致残的人类感染。基于二苯基的双(2-苯基亚氨基)咪唑烷和双胍是抗布氏锥虫(非洲锥虫病的病原体)和恶性疟原虫(严重疟疾的病原体)的极有效的抗寄生虫剂。这些化合物中的许多在治疗第一阶段非洲锥虫病的小鼠模型中也是有效的,用于开发抗锥虫病药物。另外,不同种类的双(2-亚氨基咪唑烷)和双胍已显示对其他病原体(例如细菌,真菌,寄生虫)具有抗微生物活性。由于它们的结构和物理化学性质,在生理pH下这些二元化合物易于与富含AT的DNA的小沟结合。在一些情况下,这种相互作用被认为是它们的抗微生物活性的原因。 结果:在这篇综述中,我们全面地介绍了用于在分子中引入2-氨基咪唑啉骨架的合成方法。给出这些环状胍(即未取代的,1,4-和5-取代的2-氨基咪唑啉)的合成路线是详细的。双(2-氨基咪唑啉)和双胍对动物寄生虫(布氏锥虫,克氏锥虫,利什曼原虫),疟原虫的体外和体内抗原生动物活性。和其他病原体(例如ESKAPE细菌,念珠菌属,结核分枝杆菌,多发性球菌)。最后,讨论涉及这类双阳离子化合物的抗微生物活性(例如DNA)或其它生物活性(例如α-肾上腺素能受体,咪唑啉结合位点,激酶)的靶点。
关键词: 2-(苯基亚氨基)咪唑烷,2-氨基咪唑啉的合成,环胍的合成,DNA小沟结合剂,布氏锥虫,刚果锥虫,恶性疟原虫,昏睡病。
Current Medicinal Chemistry
Title:Bis(2-aminoimidazolines) and Bisguanidines: Synthetic Approaches, Antiparasitic Activity and DNA Binding Properties
Volume: 24 Issue: 33
关键词: 2-(苯基亚氨基)咪唑烷,2-氨基咪唑啉的合成,环胍的合成,DNA小沟结合剂,布氏锥虫,刚果锥虫,恶性疟原虫,昏睡病。
摘要: Background: Parasitic diseases caused by protozoan parasites of the genus Trypanosoma and Plasmodium cause some of the deadliest and disabling human infections in tropical and subtropical areas. Diphenyl-based bis(2-phenylimino)imidazolidines and bisguanidines are extremely potent antiparasitic agents against Trypanosoma brucei (etiological agent of African trypanosomiasis) and Plasmodium falciparum (etiological agent of severe malaria). Many of these compounds are also curative in mouse models of stage 1 African trypanosomiasis representing promising leads for the development of antitrypanosomal drugs. In addition, different classes of bis(2-iminoimidazolidines) and bisguanidines have been shown to have antimicrobial activity against other pathogens (e.g. bacteria, fungi, parasitic worms). Due to their structural and physicochemical properties, these dibasic compounds, which are dications at physiological pH, are prone to bind to the minor groove of DNA at AT-rich sites. In several cases, such interaction is thought to be responsible for their antimicrobial activity.
Results: In this review, we give a comprehensive view of the synthetic methods used to introduce the 2-aminoimidazoline scaffold in a molecule. Synthetic routes that give access to these cyclic guanidines (i.e. unsubstituted, 1-, 4-, and 5-substituted 2-aminoimidazolines) are detailed. The in vitro and in vivo antiprotozoal activity of bis(2-aminoimidazolines) and bisguanidines against kinetoplastid parasites (T. brucei, T. cruzi, Leishmania), Plasmodium spp. and other pathogens (e.g. ESKAPE bacteria, Candida spp., M. tuberculosis, E. multilocularia) is also reviewed. Finally, the targets that are involved in the antimicrobial activity (e.g. DNA) or other biological activities (e.g. α-adrenergic receptors, imidazoline binding sites, kinases) of this class of dicationic compounds are discussed.
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Bis(2-aminoimidazolines) and Bisguanidines: Synthetic Approaches, Antiparasitic Activity and DNA Binding Properties, Current Medicinal Chemistry 2017; 24 (33) . https://dx.doi.org/10.2174/0929867324666170623091522
DOI https://dx.doi.org/10.2174/0929867324666170623091522 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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