药学英语Unit 6 Text A 注释及译文

Drug Discovery and Natural Products It may be argued that drug discovery is a recent concept that evolved from modern science during the 20th century, but this concept in reality dates back many centuries, and has its origins in nature. On many occasions, humans have turned to Mother Nature for cures, and discovered unique drug molecules. Thus, the term natural product has become almost synonymous with the concept of drug discovery. In modem drug discovery and development processes, natural products play an important role at the early stage of "lead" discovery, i.e. discovery of the active (determined by various bioassays) natural molecule, which itself or its structural analogues could be an ideal drug candidate.

1.origin ['ɔridʒin] n.起点，端点; 来源；出身, 血统.

2.Synonymous [sɪ'nɔnəməs]adj.同义的，类义的.

3.i.e. [,aɪ'i:] <拉> abbr. (=id est) 即，换言之.

4.candidate ['kændidit] n.申请求职者, 候选人；报考者；候选物.

有人可能认为药物发现是一个20世纪才出现的、来源于现代科学的新概念，但是事实上这个概念是源于自然界的，可以追溯到许多个世纪以前。过去，人们常常向自然母亲寻求帮助，并且找到了分子结构独特的药物。在那时，天然产物几乎是药物发现的同义词。天然产物在现代药物发现和开发过程中也发挥着重要的作用，即作为天然活性化合物（通过各种生物检定方法）的来源，而天然活性化合物或者其结构类似物可能是很好的候选药物。

Natural products have been enormous source of drugs and drug leads. It is estimated that 61 percent of the 877 small-molecular new chemical entities introduced as drugs worldwide during 1981-2002 can be traced back to or were developed from natural products. These include natural products (6 percent), natural product derivatives (27 percent), and synthetic compounds with natural-product-derived pharmacophores (5 percent) and synthetic compounds designed on the basis of knowledge gained from a natural product, i.e. a natural product mimic (23 percent). In some therapeutic areas, the contribution of natural products is even greater, e.g. about 78 percent of antibacterials and 74 percent of anticancer drug candidates are natural products or structural analogues of natural products. In 2000, approximately 60 percent of all drugs in clinical trials for the multiplicity of cancers were of natural origins. In 2001, eight (simvastatin, pravastatin, amoxycillin, clavulanic acid,

clarithromycin, azithromycin, ceftriaxone, cyclosporin and paclitaxel) of 30 top selling medicines were natural products or derived from natural products, and despite being neglected by the pharmaceutical companies, these eight drugs together totaled $16 billion in sales.

1. entity ['entiti] n.实体, 独立存在体, 实际存在物.

2. derivative [di'rivətiv]

n.派生物, 引出物，衍生物adj.模仿他人的; 衍生的; 派生的

3. pharmacophore ['fɑ:məkəfɔ:] n.药效基团

4. multiplicity [,mʌlti'plisiti] n.多样性

天然产物已经成为药物或先导化合物的重要来源。据统计，在1981年至2002年间新发现的、在全世界广泛应用的877种小分子药物中，有61%与天然产物有关或者源于天然产物。其中直接来自于天然产物的占6%；天然产物的衍生物占27%；根据天然产物药效团合成的化合物占5%；基于对天然产物的认识设计、合成的化合物，即模拟天然产物的合成化合物，占23%。甚至于在某些治疗领域天然产物的贡献更大，例如78%的抗生素类候选药物和74%抗癌类候选药物是天然产物或其结构类似物。在2000年，进行到临床试验阶段的用于治疗多重癌的药物中，大约有60%是天然来源的。在2001年，药品销售额前30强中，源于天然产物的药物或天然产物类似物就占了8席（辛伐他汀、帕伐他汀、阿莫西林、克拉维酸、克拉霉素、阿奇霉素、头孢曲松、环孢菌素和紫杉醇）。尽管制药公司对这一点的认识尚有不足，但是这8种药物的销售总额已经达到了160亿美元。

Despite the impressive record and statistics regarding the success of natural products in drug discovery, "natural product drug discovery" has been neglected by many big pharmaceutical companies in the recent past. The declining popularity of natural products as a source of new drugs began in the 1990s, because of some practical factors, e.g. the apparent lack of compatibility of natural products with the modern high throughput screening (HTS) programs, where significant degrees of automation, robotics and computers are used, the complexity in the isolation and identification of natural products and the cost and time involved in the natural product "lead" discovery process. Complexity in the chemistry of natural products, especially in the case of novel structural types, also became the rate-determining step in drug discovery programs. Attempts to discover new drug "leads" from natural sources has never stopped, despite being neglected by the pharmaceutical companies, but