Kim Soyoung, Salim Angela A, Swanson Steven M, Kinghorn A Douglas
Program for Collaborative Research in the Pharameutical Sciences and Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA.
Anticancer Agents Med Chem. 2006 Jul;6(4):319-45. doi: 10.2174/187152006777698123.
During the past few years, a group of cyclopenta[b]benzofurans from the plant genus Aglaia has received broad scientific attention as interesting natural product lead compounds with potential anticancer and insecticidal activities. Since the first cyclopenta[b]benzofuran derivative, rocaglamide, from Aglaia elliptifolia, was found to exhibit antileukemic activity in a murine in vivo model, the genus Aglaia has been subjected to further investigation. Over 40 cyclopenta[b]benzofurans have been tested against different human cancer cell lines, and the cumulative results provide some important clues as to how to improve their activity through modification of their chemical structures. The semisynthesis and total synthesis of the cyclopenta[b]benzofurans have been conducted. Although the ultimate molecular target(s) responsible for their antiproliferative activity has not yet been identified, studies on their cellular mechanism of action have demonstrated that some of these compounds inhibit TNF-alpha or PMA-induced NF-kappaB activity in T-lymphocytes and induce apoptosis in different human cancer cell lines. Based on the published data thus far, cyclopenta[b]benzofurans offer excellent potential as therapeutic agent candidates in cancer chemotherapy, even if much work still remains to be done for their further development.
在过去几年中,来自米仔兰属植物的一组环戊并[b]苯并呋喃作为具有潜在抗癌和杀虫活性的有趣天然产物先导化合物受到了广泛的科学关注。自从从椭圆叶米仔兰中发现首个环戊并[b]苯并呋喃衍生物洛卡酰胺在小鼠体内模型中表现出抗白血病活性以来,米仔兰属植物受到了进一步研究。超过40种环戊并[b]苯并呋喃已针对不同的人类癌细胞系进行了测试,累积结果为如何通过化学结构修饰来提高其活性提供了一些重要线索。环戊并[b]苯并呋喃的半合成和全合成已经开展。尽管尚未确定其抗增殖活性的最终分子靶点,但对其细胞作用机制的研究表明,其中一些化合物可抑制T淋巴细胞中肿瘤坏死因子-α或佛波酯诱导的核因子-κB活性,并在不同的人类癌细胞系中诱导凋亡。基于目前已发表的数据,环戊并[b]苯并呋喃作为癌症化疗候选治疗药物具有巨大潜力,即便其进一步开发仍有大量工作有待完成。