Rishton Gilbert M
Channel Islands Alzheimer's Institute, California State University, Camarillo, CA 93012, USA.
Am J Cardiol. 2008 May 22;101(10A):43D-49D. doi: 10.1016/j.amjcard.2008.02.007.
The history of drug development has its foundation firmly set in the study of natural remedies used to treat human disease over centuries. Analysis of medicinal plants, bioactive cultures, and increased understanding of micronutrients in the food chain opened the door to the development of purified and defined chemical compounds as dose-controlled medicines. Thus, with the early discovery of cardiotonics in foxglove, salicylic acid in willow bark, morphine in poppies, and penicillin in mold, the pharmaceutical industry was launched. Such natural small molecules served as treatments for disease and ultimately, as pharmacologic tools to enable the understanding of the biochemical pathways and mechanisms of disease. In contrast, modern drug discovery technologies coupled with the powerful tools of biotechnology have prompted drug discovery organizations to focus on target-driven drug discovery at the molecular level by launching high-throughput screening programs using artificial biochemical assays. At a time when the pharmaceutical industry has come under scrutiny for high rates of drug development failure, it is interesting to see that natural products drug discovery has been marginalized in favor of this high-throughput biochemical screening paradigm. If modern drug development is once again to benefit from natural products as a source, then the limitations of artificial biochemical assays as applied to the screening of natural extracts must be realized in order to capitalize on the vast natural molecular diversity and rich ethnobotanic data that has emerged worldwide. Natural compounds can again become central players in the treatment of disease and in the understanding of disease mechanisms.
药物研发的历史深深扎根于对数百年来用于治疗人类疾病的天然疗法的研究。对药用植物、生物活性培养物的分析以及对食物链中微量营养素认识的加深，为开发纯化且明确的化合物作为剂量可控的药物打开了大门。因此，随着洋地黄中强心剂、柳树皮中水杨酸、罂粟中吗啡以及霉菌中青霉素的早期发现，制药行业得以兴起。这些天然小分子成为了疾病的治疗手段，最终还成为了有助于理解疾病生化途径和机制的药理学工具。相比之下，现代药物发现技术与生物技术的强大工具相结合，促使药物发现机构通过开展使用人工生化检测的高通量筛选项目，在分子层面专注于靶点驱动的药物发现。在制药行业因药物研发失败率高而受到审视之际，有趣的是天然产物药物发现已被边缘化，转而青睐这种高通量生化筛选模式。如果现代药物研发要再次从天然产物这一来源中获益，那么就必须认识到应用于天然提取物筛选的人工生化检测的局限性，以便利用全球范围内出现的巨大天然分子多样性和丰富的民族植物学数据。天然化合物能够再次成为疾病治疗以及疾病机制理解中的核心要素。
