Oberlies Nicholas H, Kroll David J
Natural Products Laboratory, Research Triangle Institute, P.O. Box 12194, Research Triangle Park, North Carolina 27709-2194, USA.
J Nat Prod. 2004 Feb;67(2):129-35. doi: 10.1021/np030498t.
The research team of Dr. Monroe E. Wall and Dr. Mansukh C. Wani of Research Triangle Institute discovered two first-in-class life-saving chemotherapeutic agents. Camptothecin, first isolated and identified from Camptotheca acuminata, was found to kill cancer cells uniquely via topoisomerase I poisoning. Presently, two first-generation analogues of camptothecin are used to treat ovarian, colorectal, and small-cell lung cancers, and several second-generation analogues are in clinical trials. Taxol, first isolated and identified by Wall and Wani from Taxus brevifolia, was found to inhibit cancer cell growth via the stabilization of microtubules. In 1992, taxol was approved for refractory ovarian cancer and today is used against breast and non-small cell lung cancers and in Kaposi's sarcoma. While there have been numerous reviews of these molecules individually, this review offers an integrated account of the research team of "Wall and Wani" and the significance of their discoveries to chemistry, biology, and clinical medicine.
三角研究园的门罗·E·沃尔博士和曼苏克·C·瓦尼博士的研究团队发现了两种一流的挽救生命的化疗药物。喜树碱最初是从喜树中分离并鉴定出来的,它被发现通过毒害拓扑异构酶I独特地杀死癌细胞。目前,喜树碱的两种第一代类似物被用于治疗卵巢癌、结直肠癌和小细胞肺癌,还有几种第二代类似物正在进行临床试验。紫杉醇最初是由沃尔和瓦尼从短叶红豆杉中分离并鉴定出来的,它被发现通过稳定微管来抑制癌细胞生长。1992年,紫杉醇被批准用于治疗难治性卵巢癌,如今它被用于治疗乳腺癌和非小细胞肺癌以及卡波西肉瘤。虽然已经有许多关于这些分子的单独综述,但本综述全面介绍了“沃尔和瓦尼”研究团队以及他们的发现对化学、生物学和临床医学的重要性。