通过结构修饰从天然产物中洞察药物发现

Insights into drug discovery from natural products through structural modification.

作者信息

Chen Jichao, Li Wenlong, Yao Hequan, Xu Jinyi

机构信息

State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China; Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.

出版信息

Fitoterapia. 2015 Jun;103:231-41. doi: 10.1016/j.fitote.2015.04.012. Epub 2015 Apr 24.

DOI:10.1016/j.fitote.2015.04.012

PMID:25917513

Abstract

Natural products (NPs) have played a key role in drug discovery and are still a prolific source of novel lead compounds or pharmacophores for medicinal chemistry. Pharmacological activity and druggability are two indispensable components advancing NPs from leads to drugs. Although naturally active substances are usually good lead compounds, most of them can hardly satisfy the demands for druggability. Hence, these structural phenotypes have to be modified and optimized to overcome existing deficiencies and shortcomings. This review illustrates druggability optimization of NPs through structural modification with some successful examples.

摘要

天然产物在药物发现中发挥了关键作用，并且仍然是药物化学中新型先导化合物或药效团的丰富来源。药理活性和成药性是推动天然产物从先导物发展为药物的两个不可或缺的组成部分。尽管天然活性物质通常是良好的先导化合物，但它们中的大多数很难满足成药性的要求。因此，必须对这些结构表型进行修饰和优化，以克服现有的缺陷和不足。本综述通过一些成功的例子说明了通过结构修饰对天然产物进行成药性优化。