Gordaliza M
Departamento de Química Farmacéutica, Facultad de Farmacia, Universidad de Salamanca, Salamanca, Spain.
Clin Transl Oncol. 2007 Dec;9(12):767-76. doi: 10.1007/s12094-007-0138-9.
Throughout history, natural products have afforded a rich source of compounds that have found many applications in the fields of medicine, pharmacy and biology. Within the sphere of cancer, a number of important new commercialised drugs have been obtained from natural sources, by structural modification of natural compounds, or by the synthesis of new compounds, designed following a natural compound as model. The search for improved cytotoxic agents continues to be an important line in the discovery of modern anticancer drugs. The huge structural diversity of natural compounds and their bioactivity potential have meant that several products isolated from plants, marine flora and microorganisms can serve as "lead" compounds for improvement of their therapeutic potential by molecular modification. Additionally, semisynthesis processes of new compounds, obtained by molecular modification of the functional groups of lead compounds, are able to generate structural analogues with greater pharmacological activity and with fewer side effects. These processes, complemented with high-throughput screening protocols, combinatorial chemistry, computational chemistry and bioinformatics are able to afford compounds that are far more efficient than those currently used in clinical practice. Combinatorial biosynthesis is also applied for the modification of natural microbial products. Likewise, advances in genomics and the advent of biotechnology have improved both the discovery and production of new natural compounds.
纵观历史,天然产物提供了丰富的化合物来源,这些化合物在医学、药学和生物学领域有诸多应用。在癌症领域,一些重要的新型商业化药物已从天然来源获得,通过对天然化合物进行结构修饰,或通过以天然化合物为模型设计合成新化合物。寻找更有效的细胞毒性药物仍然是现代抗癌药物发现中的一条重要路线。天然化合物巨大的结构多样性及其生物活性潜力意味着,从植物、海洋植物群和微生物中分离出的几种产物可作为“先导”化合物,通过分子修饰提高其治疗潜力。此外,通过对先导化合物的官能团进行分子修饰获得新化合物的半合成过程,能够产生具有更高药理活性和更少副作用的结构类似物。这些过程与高通量筛选方案、组合化学、计算化学和生物信息学相结合,能够提供比目前临床实践中使用的化合物效率更高的化合物。组合生物合成也应用于天然微生物产物的修饰。同样,基因组学的进展和生物技术的出现改善了新天然化合物的发现和生产。