Leeds Jennifer A, Schmitt Esther K, Krastel Philipp
Infectious Diseases Area, Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA.
Expert Opin Investig Drugs. 2006 Mar;15(3):211-26. doi: 10.1517/13543784.15.3.211.
The pharmaceutical industry has historically relied on nature to provide compounds for antibacterial drug discovery. In recent years, several pharmaceutical companies have scaled back their efforts in natural product research. Nevertheless, the screening of natural products for antibacterial activity continues to provide excellent sources of biologically and chemically informative leads for new drugs. New technologies in high-throughput cultivation, genetic approaches to biodiversity and discovery of relatively untapped sources of natural products are expanding the ability to find novel, potent and highly selective antibacterial structures. Advances in purification, dereplication and structure elucidation, combined with the ability to chemically or biologically derivatise hits, aim to make the timeline for natural product-derived drug discovery similar or shorter than that expected for small synthetic molecules. This review addresses the strengths and shortcomings of technologies focused on microbe-derived natural products for antibacterial drug discovery and stresses the need for commitment to these approaches in order to achieve the goal of delivering safe, efficacious and high-quality medicines in the long run.
制药行业历来依靠自然界提供用于抗菌药物研发的化合物。近年来,几家制药公司已缩减其在天然产物研究方面的工作。尽管如此,对天然产物进行抗菌活性筛选仍继续为新药提供生物学和化学信息丰富的优质先导化合物来源。高通量培养新技术、生物多样性的基因方法以及相对未开发的天然产物来源的发现,正在扩大发现新型、强效和高选择性抗菌结构的能力。纯化、去重复和结构解析方面的进展,再加上对命中化合物进行化学或生物学衍生化的能力,旨在使天然产物衍生药物研发的时间线与小合成分子预期的时间线相似或更短。本综述阐述了专注于微生物衍生天然产物用于抗菌药物研发的技术的优势与不足,并强调为了长期实现提供安全、有效和高质量药物的目标,必须致力于这些方法。