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噻唑烷酮类骨架作为弓形虫病新治疗策略的研究进展

A Perspective on Thiazolidinone Scaffold Development as a New Therapeutic Strategy for Toxoplasmosis.

机构信息

Centre for Biomedical Research CIBM, University of Quindío, Armenia, Colombia.

Dentistry Faculty, University Antonio Nariño, Armenia, Colombia.

出版信息

Front Cell Infect Microbiol. 2018 Oct 16;8:360. doi: 10.3389/fcimb.2018.00360. eCollection 2018.

DOI:10.3389/fcimb.2018.00360
PMID:30386743
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6198644/
Abstract

is one of the most successful parasites due to its ability to infect a wide variety of warm-blooded animals. It is estimated that one-third of the world's population is latently infected. The generic therapy for toxoplasmosis has been a combination of antifolates such as pyrimethamine or trimethoprim with either sulfadiazine or antibiotics such as clindamycin with a combination with leucovorin to prevent hematologic toxicity. This therapy shows limitations such as drug intolerance, low bioavailability or drug resistance by the parasite. There is a need for the development of new molecules with the capacity to block any stage of the parasite's life cycle in humans or in a different type of hosts. Heterocyclic compounds are promissory drugs due to its reported biological activity; for this reason, thiazolidinone and its derivatives are presented as a new alternative not only for its inhibitory activity against the parasite but also for its high selectivity-level with high therapeutic index. Thiazolidinones are an important scaffold known to be associated with anticancer, antibacterial, antifungal, antiviral, antioxidant, and antidiabetic activities. The molecule possesses an imidazole ring that has been described as an antiprotozoal agent with antiparasitic properties and less toxicity. Thiazolidinone derivatives have been reportedly as building blocks in organic chemistry and as scaffolds for drug discovery. Here we present a perspective of how structural modifications of the thiazolidinone core could generate new compounds with high anti-parasitic effect and less toxic results.

摘要

弓形虫是最成功的寄生虫之一,因为它能够感染各种各样的温血动物。据估计,世界上有三分之一的人口处于潜伏感染状态。弓形虫病的一般治疗方法是将抗叶酸类药物(如嘧啶和三甲氧苄啶)与磺胺嘧啶或克林霉素等抗生素联合使用,并结合亚叶酸预防血液毒性。这种治疗方法存在一些局限性,如药物不耐受、生物利用度低或寄生虫耐药性。因此,需要开发新的分子,这些分子有能力在人类或不同类型的宿主中阻断寄生虫生命周期的任何阶段。杂环化合物是一种很有前途的药物,因为它们具有报道的生物活性;出于这个原因,噻唑烷酮及其衍生物不仅因其对寄生虫的抑制活性,而且因其高选择性水平和高治疗指数而被视为一种新的替代药物。噻唑烷酮是一种重要的支架,已知与抗癌、抗菌、抗真菌、抗病毒、抗氧化和抗糖尿病活性有关。该分子含有一个咪唑环,被描述为具有抗寄生虫特性和较低毒性的抗原生动物药物。噻唑烷酮衍生物已被报道作为有机化学中的构建块和药物发现的支架。在这里,我们提出了一种观点,即如何通过对噻唑烷酮核心的结构修饰来生成具有高抗寄生虫效果和较低毒性的新化合物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2124/6198644/ed4919f4e739/fcimb-08-00360-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2124/6198644/65ae72f26c9c/fcimb-08-00360-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2124/6198644/ed4919f4e739/fcimb-08-00360-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2124/6198644/65ae72f26c9c/fcimb-08-00360-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2124/6198644/ed4919f4e739/fcimb-08-00360-g0002.jpg

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