摘要
被忽视的热带病每年造成50多万人死亡,并以多重残疾为特征。利什曼病和南美锥虫病是最严重的热带传染病,分别由利什曼原虫和克氏锥虫引起。葡聚糖酶、喷他脒和米替福辛通常用于治疗利什曼病,而硝呋替莫、苄硝唑是目前治疗恰加斯病的药物。然而,这些治疗与耐药性和严重的副作用有关。因此,开发合成产品,特别是含有N02、F或Cl的产品,可以提高生物活性。目前的工作总结了硝基、氯和氟合成衍生物抗利什曼原虫和抗锥虫体活性的信息。在SciFinder、Wiley、Science Direct、PubMed、ACS、施普林格、Scielo等数据库中手工检索与抗利氏虫和抗锥虫活性相关的卤化衍生物的科学出版物。根据文献资料,根据体外研究的IC50/EC50值,预测了90多个化合物为铅分子。值得一提的是,本研究只考虑了已知对哺乳动物细胞有细胞毒性作用的活性化合物。观察到的活性归因于在化合物主链中存在硝基、氟和氯基团。总之,硝基和卤化衍生物是抗利什曼原虫和抗锥虫体的活性化合物,可以作为开发抗利什曼病和南美锥虫病新药的基础。然而,活性合成化合物的体外和体内毒性研究仍然是需要的。这些有发展前景的化合物的药代动力学研究和作用机理有待进一步探索。新的催化剂的使用和化学转化可以提供未开发的卤代化合物具有更好的抗利什曼和抗锥虫活性。
关键词: 被忽视的热带病、硝基、卤化衍生物、利什曼病、南美锥虫病、合成化合物
Current Drug Targets
Title:The Role of Nitro (NO2-), Chloro (Cl), and Fluoro (F) Substitution in the Design of Antileishmanial and Antichagasic Compounds
Volume: 22 Issue: 4
关键词: 被忽视的热带病、硝基、卤化衍生物、利什曼病、南美锥虫病、合成化合物
摘要: Neglected tropical diseases (NTDs) are responsible for over 500,000 deaths annually and are characterized by multiple disabilities. Leishmaniasis and Chagas diseases are among the most severe NTDs, and are caused by the Leishmania sp and Trypanosoma cruzi, respectively. Glucantime, pentamidine, and miltefosine are commonly used to treat leishmaniasis, whereas nifurtimox, benznidazole are current treatments for Chagas disease. However, these treatments are associated with drug resistance and severe side effects. Hence, the development of synthetic products, especially those containing N02, F, or Cl, are known to improve biological activity. The present work summarizes the information on the antileishmanial and antitrypanosomal activity of nitro-, chloro-, and fluorosynthetic derivatives. Scientific publications referring to halogenated derivatives in relation to antileishmanial and antitrypanosomal activities were hand-searched in databases such as SciFinder, Wiley, Science Direct, PubMed, ACS, Springer, Scielo, and so on. According to the literature information, more than 90 compounds were predicted as lead molecules with reference to their IC50/EC50 values in in vitro studies. It is worth mentioning that only active compounds with known cytotoxic effects against mammalian cells were considered in the present study. The observed activity was attributed to the presence of nitro-, fluoro-, and chloro-groups in the compound backbone. All in all, nitro and halogenated derivatives are active antileishmanial and antitrypanosomal compounds and can serve as the baseline for the development of new drugs against leishmaniasis and Chagas disease. However, efforts in in vitro and in vivo toxicity studies of the active synthetic compounds is still needed. Pharmacokinetic studies and the mechanism of action of the promising compounds need to be explored. The use of new catalysts and chemical transformation can afford unexplored halogenated compounds with improved antileishmanial and antitrypanosomal activity.
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The Role of Nitro (NO2-), Chloro (Cl), and Fluoro (F) Substitution in the Design of Antileishmanial and Antichagasic Compounds, Current Drug Targets 2021; 22 (4) . https://dx.doi.org/10.2174/1389450121666201228122239
DOI https://dx.doi.org/10.2174/1389450121666201228122239 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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