达特茅斯大学的研究人员进行了首次特定合成参与白血病细胞死亡的某种化合物的研究。
该发现发表在《Angewandte Chemie International Edition》杂志上。
“我们预计，这些化合物将作为一种重要且有用的工具用来检查一种重要的调节细胞凋亡但还未定义的阶段。”副教授Jimmy Wu说，“研究表明他们研究的生物机制正在进行。”
研究人员完成了黄睡莲生物碱二聚体家族几种成员的总分析，这些化合物首次是从美洲黄连花中分离出来的。这些结构复杂的分子可诱导某些人类白血病细胞的细胞凋亡、程序性细胞死亡的速度比其他小分子要快。研究人员还可以合成一些相关的结构，他们预测在自然中可能存在但尚未被发现。
仅有两份报告目前试图解释这些分子的生物作用机理。但这些都是不完整的，还需要更多的研究来全面揭示这些化合物是如何工作的。Dartmouth团队现在提供了一种方法稳定供应活性化合物进行进一步的研究。Alan Eastman教授进行初步生物测试，研究表明所有的化合物包括天然的和预测广泛存在于自然界中的，能够诱导白血病细胞极其迅速的凋亡。研究人员正在研究其生物作用机制。
“不充分的细胞凋亡与癌症和自身免疫性疾病密切相关，”wu说。“有许多疾病与过度细胞死亡相关，如艾滋病、阿尔茨海默氏症，亨廷顿氏舞蹈症，帕金森疾病和肌肉萎缩性侧面硬化病。更好的理解生物学基础有关黄睡莲生物碱二聚体如何可以如此迅速的诱导细胞死亡，可能导致有关潜在疗法的设计和异常细胞凋亡疾病的干预的异常点。”
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Total Syntheses and Biological evaluation of Both Enantiomers of Several Hydroxylated Dimeric Nuphar Alkaloids†.
Jimmy Wu et al.
Dartmouth researchers and their colleagues have carried out the first total syntheses of certain compounds involved in excessive cell death in leukemia. The findings appear in the journal Angewandte Chemie International Edition. "We anticipate that these compounds will serve as useful tools for dissecting an important but as yet undefined step in the regulation of apoptosis," says senior author Jimmy Wu, an associate professor of chemistry at Dartmouth. "Studies to clarify the biological mechanism by which they operate are ongoing."The researchers completed the total syntheses of several members of the family of dimeric nuphar alkaloids, which are compounds previously isolated from the yellow pond lily. These are structurally complex molecules that are capable of including apoptosis, or programmed cell death, in certain human leukemia cell lines faster than any other small molecule. The researchers also were able to synthesize some related structures that they predict might exist in nature but have not yet been found.