Neves Bruno J, Andrade Carolina H, Cravo Pedro V L
LabMol-Laboratory for Drug Design and Molecular Modeling, Faculdade de Farmácia, Universidade Federal de Goiás, Goiânia 74605-170, Brazil.
GenoBio-Laboratory of Genomics and Biotechnology, Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia 74605-050, Brazil.
Molecules. 2015 Jan 23;20(2):1872-903. doi: 10.3390/molecules20021872.
Schistosomiasis is a neglected parasitic tropical disease that claims around 200,000 human lives every year. Praziquantel (PZQ), the only drug recommended by the World Health Organization for the treatment and control of human schistosomiasis, is now facing the threat of drug resistance, indicating the urgent need for new effective compounds to treat this disease. Therefore, globally, there is renewed interest in natural products (NPs) as a starting point for drug discovery and development for schistosomiasis. Recent advances in genomics, proteomics, bioinformatics, and cheminformatics have brought about unprecedented opportunities for the rapid and more cost-effective discovery of new bioactive compounds against neglected tropical diseases. This review highlights the main contributions that NP drug discovery and development have made in the treatment of schistosomiasis and it discusses how integration with virtual screening (VS) strategies may contribute to accelerating the development of new schistosomidal leads, especially through the identification of unexplored, biologically active chemical scaffolds and structural optimization of NPs with previously established activity.
血吸虫病是一种被忽视的热带寄生虫病,每年导致约20万人死亡。吡喹酮(PZQ)是世界卫生组织推荐的唯一用于治疗和控制人类血吸虫病的药物,目前正面临耐药性威胁,这表明迫切需要新的有效化合物来治疗这种疾病。因此,在全球范围内,天然产物(NPs)作为血吸虫病药物发现和开发的起点再次受到关注。基因组学、蛋白质组学、生物信息学和化学信息学的最新进展为快速、更具成本效益地发现针对被忽视热带病的新生物活性化合物带来了前所未有的机遇。本综述重点介绍了天然产物药物发现和开发在血吸虫病治疗方面的主要贡献,并讨论了与虚拟筛选(VS)策略相结合如何有助于加速新型抗血吸虫先导化合物的开发,特别是通过识别未被探索的生物活性化学支架以及对具有先前已确定活性的天然产物进行结构优化。