Potential of cyclopenta[b]benzofurans from Aglaia species in cancer chemotherapy
Potential of cyclopenta[b]benzofurans from Aglaia species in cancer chemotherapy
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DOI：
10.2174/187152006777698123
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发表时间：
2006-07-01
影响因子：
2.8
通讯作者：
Kinghorn, A. Douglas
中科院分区：
文献类型：
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作者：
Kim, Soyoung;Salim, Angela A.;Kinghorn, A. Douglas
近年来，一组来自米仔兰属植物的环戊二烯并[B]苯并呋喃类化合物作为具有潜在抗癌和杀虫活性的天然先导化合物受到了广泛的关注。自从第一个环戊二烯并[B]苯并呋喃衍生物，罗格列胺，从米仔兰，被发现在小鼠体内模型中表现出抗白血病活性，米仔兰属已受到进一步的调查。超过40种环戊二烯并[B]苯并呋喃已经针对不同的人类癌细胞系进行了测试，累积的结果为如何通过修饰其化学结构来提高其活性提供了一些重要的线索。对环戊二烯并[h]苯并呋喃类化合物进行了半合成和全合成。尽管负责其抗增殖活性的最终分子靶标尚未被鉴定，但对它们的细胞作用机制的研究已经证明，这些化合物中的一些抑制T淋巴细胞中TNF-α或PMA诱导的NF-κ B活性，并诱导不同人类癌细胞系中的细胞凋亡。基于迄今为止发表的数据，环戊二烯并[B]苯并呋喃作为癌症化疗的治疗剂候选物提供了优异的潜力，即使对于它们的进一步开发仍有许多工作要做。
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[h]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-kappa B 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.