Departamento de Ciencias Farmaceuticas, Centro de Ciencias da Saude, Universidade Federal de Pernambuco, 50740-520, Recife, PE, Brazil.
Colegiado de Nutricao, Campus Petrolina, Universidade de Pernambuco, 56328-903, Petrolina, PE, Brazil.
Curr Med Chem. 2019;26(23):4323-4354. doi: 10.2174/0929867324666171023163752.
Privileged motifs are recurring in a wide range of biologically active compounds that reach different pharmaceutical targets and pathways and could represent a suitable start point to access potential candidates in the neglected diseases field. The current therapies to treat these diseases are based in drugs that lack of the desired effectiveness, affordable methods of synthesis and allow a way to emergence of resistant strains. Due the lack of financial return, only few pharmaceutical companies have been investing in research for new therapeutics for neglected diseases (ND).
Based on the literature search from 2002 to 2016, we discuss how six privileged motifs, focusing phthalimide, isatin, indole, thiosemicarbazone, thiazole, and thiazolidinone are particularly recurrent in compounds active against some of neglected diseases.
It was observed that attention was paid particularly for Chagas disease, malaria, tuberculosis, schistosomiasis, leishmaniasis, dengue, African sleeping sickness (Human African Trypanosomiasis - HAT) and toxoplasmosis. It was possible to verify that, among the ND, antitrypanosomal and antiplasmodial activities were between the most searched. Besides, thiosemicarbazone moiety seems to be the most versatile and frequently explored scaffold. As well, phthalimide, isatin, thiazole, and thiazolidone nucleus have been also explored in the ND field.
Some described compounds, appear to be promising drug candidates, while others could represent a valuable inspiration in the research for new lead compounds.
特权基序在广泛的具有生物活性的化合物中反复出现,这些化合物可作用于不同的药物靶点和通路,因此可能成为探索被忽视疾病领域潜在候选药物的合适起点。目前用于治疗这些疾病的疗法所基于的药物缺乏所需的疗效、经济实惠的合成方法,并且容易产生耐药菌株。由于缺乏经济回报,只有少数制药公司一直在为治疗被忽视疾病(ND)的新疗法进行研究。
基于 2002 年至 2016 年的文献检索,我们讨论了六个特权基序(邻苯二甲酰亚胺、靛红、吲哚、硫代缩氨基脲、噻唑和噻唑烷酮)如何特别频繁地出现在针对某些被忽视疾病的活性化合物中。
我们观察到,人们特别关注恰加斯病、疟疾、结核病、血吸虫病、利什曼病、登革热、非洲昏睡病(人类非洲锥虫病-HAT)和弓形体病。可以验证的是,在 ND 中,抗锥虫和抗疟活性是研究最多的。此外,硫代缩氨基脲部分似乎是最通用和经常探索的支架。同样,邻苯二甲酰亚胺、靛红、噻唑和噻唑烷酮核也在 ND 领域得到了探索。
一些描述的化合物似乎是有前途的候选药物,而另一些化合物可能为新的先导化合物的研究提供有价值的启示。