Field: Plant & Animal Science
Article Title: The role of natural product chemistry in drug discovery
Authors: Butler, MS
Journal: J NAT PROD
Volume: 67
Issue: 12
Page: 2141-2153
Q：Why do you think your paper is highly cited?
A ：The paper is highly cited because at the time of publication there were few "up-to-date" reviews of the role of natural product chemistry in drug discovery. In addition, the review discusses the impact of natural product-derived drugs in terms of drug sales, as well as giving a snapshot of natural product-derived drugs in clinical trials and cutting edge techniques used in the field. Finally, the Journal of Natural Products has a wide readership outside of the field and is easily accessible on-line through ACS (American Chemical Society).
Q：Does it describe a new discovery or a new methodology that's useful to others?
A ：No, as the paper is a review the methodologies described are not new as such. However, the methods reviewed may be new to many readers and useful for groups who want to quicken the pace of their research.
Q： Could you summarize the significance of your paper in layman's terms?
A ：Despite natural products traditionally playing an important role in drug discovery, most pharmaceutical companies have either terminated or considerably scaled down their natural product operations. This is despite approximately 50% of drugs being natural products, semi-synthetic derivatives of natural products, or synthetic compounds derived from a natural product lead structure.
In addition, a significant number of natural product-derived drugs are ranked in the top 35 worldwide selling ethical drugs or are in late-stage clinical development. The failure of alternative drug discovery methods to deliver many lead compounds in key therapeutic areas like immunosuppression, anti-infectives, and metabolic diseases has led to a renewed interest in natural product research. However, in order to continue to be competitive with other drug discovery methods, continual improvements in the speed of the screening, isolation, and structure elucidation processes are required.
Also, the suitability of screens for natural product extracts and issues involved with large-scale compound supply by synthesis, semi-synthesis, or biological means, needs to be considered. By taking into account all of these factors, natural product chemistry will have an important place in drug discovery side by side with other techniques.
Q：How did you become involved in this research, and were any problems encountered along the way?
A ：I became involved with natural product drug discovery as an extension of my Ph.D. studies in marine natural products at The University of Melbourne and postdoctoral work in the Cancer Research Institute at Arizona State University. I was first involved in industrial drug discovery within the Griffith University/AstraZeneca collaboration in Briane, Australia, before heading to Singapore in 1999 to head the chemistry group at the Centre for Natural Product Research, which collaborated with GlaxoithKline. In 2002, the Centre for Natural Product Research corporatized to become MerLion Pharmaceuticals where I continue to work today as Director of Natural Product Chemistry.
Q： If applicable, what are the social or political implications of your research?
A ：It is important that state-of-the-art natural product research continues to flourish in academic and industrial laboratories so that new, novel, biologically-active templates can be discovered. Unfortunately, in the last few years, funding has been extremely difficult to obtain for many researchers and, as a result, many laboratories don't have access to key technological advances. Finally, many universities, even those which traditionally were strong in natural product research, no longer employ natural products chemists, which in the longer term will lead to a shortage of people who possess cutting edge skills.
Dr. Mark S. Butler
Director Natural Product Chemistry
MerLion Pharmaceuticals
Singapore
And
Adjunct Associate Professor
Department of Chemistry
National University of Singapore
Singapore
Q：你觉得为什么你的论文引用率会这么高？
A：我的论文引用率高是因为在当时的期刊很少有关于“天然产物化学在药物发现中的作用”的最新综述。此外，这篇综述讨论了天然产物衍生化药物对药物销售的影响，并且在该领域使用的临床实验和先进技术中，给予了天然产物衍生化药物一个快报（snapshot）。最后，是因为天然产物杂志（the Journal of Natural Products）在非该领域中有很广泛的读者群并且人们很容易通过美国化学协会（ACS）在线获取该杂志全文。
Q：那对于其他领域，该文章是否描述了一个新发现或新的方法学呢？
A:：不，综述中描述的方法学不是新的。但是，文中综述的方法对多数读者来说可能是新的，并且对于那些想加快自己研究进度的研究团队来说，这种方法很有用。
Q：你能用简单的语言概述一下你论文的意义吗？
A：尽管天然产物传统上在药物发现中起着重要作用，并且大约50％的药物来源于天然产物、天然产物半合成衍生物及天然先导化合物的合成物，但是大多数药物公司要么就是终止，要么就是大规模地删减天然产物的研究与开发。
此外，很多天然产物衍生化药物处于世界处方药物销售的前35名或者处于临床后期试验。在热点的治疗领域，如免疫抑制、抗感染及代谢疾病中，用于发现更多先导化合物的选择性药物发现方法的局限，使得人们开始热衷于天然产物的研究。但是，为了与其他药物发现方法继续竞争，天然产物研究方法中的筛选速度、分离、化合物结构鉴定的改进是必需的。
另外，天然产物提取液的筛选适应性以及通过合成、半合成或生物学手段提供大规模化合物有关的问题需要考虑。处理好了这些因素，在药物发现过程中，天然产物化学将会与其他技术一样处于一个重要的地位。
Q：你是怎样从事你的研究的？在研究过程中遇到过困难吗？
A：我从事天然产物药物开发研究是作为在墨尔本大学读海洋天然产物方向的博士以及亚利桑那州立大学肿瘤研究所做博士后工作的延伸而进行研究的。在1999年前往新加坡加入与GlaxoithKline（应该是一个机构）合作的天然产物研究中心的化学研究团队前，我在澳大利亚Briane（澳大利亚的一个地区）的Griffith大学/AstraZeneca合作项目中第一次从事药物发现的工业化研究。2002年，天然产物研究中心合并为MerLion药物研究所，我留在那继续工作一直到现在成为一个天然产物化学的********。
Q：如果有应用价值，你的研究会有怎样的社会或政治意义？
A：天然产物研究的知识水平不断地丰富和繁荣理论及工业实验，这是很重要的，以至于结构新的、新颖的以及具有生物活性的天然产物得以发现。不幸的是，在最近几年很多学者研究经费申请困难，结果很多实验室无法使核心技术得以改进。最终，很多大学，甚至之前在天然产物研究方面有很强优势的大学不再聘任天然产物化学家，时间久了，这势必会造成拥有先进技能专家的缺失。
