Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, Ji'nan, Shandong, China.
Bioorg Med Chem Lett. 2011 Dec 1;21(23):7025-9. doi: 10.1016/j.bmcl.2011.09.103. Epub 2011 Oct 1.
A series of novel nitric oxide-releasing tamibarotene derivatives were synthesized by coupling nitric oxide (NO) donors with tamibarotene via various spacers, and were evaluated for their antiproliferative activities against human leukemic HL-60, NB4 and K562 cell lines in vitro. The test results showed that three compounds (7g, 9a and 9e) exhibited more potent antileukemic activity than the control tamibarotene. Furthermore, the preliminary structure-activity analysis revealed that amino acids serving as spacers could bring about significantly improved biological activities of NO donor hybrids. These interesting results could provide new insights into the development of NO-based antileukemic agents.
一系列新型的一氧化氮供体型他米巴罗汀衍生物通过各种连接基团将一氧化氮（NO）供体与他米巴罗汀偶联而成，其体外抗人白血病 HL-60、NB4 和 K562 细胞系的增殖活性进行了评价。试验结果表明，有 3 种化合物（7g、9a 和 9e）比对照他米巴罗汀具有更强的抗白血病活性。此外，初步的构效关系分析表明，作为连接基团的氨基酸可以显著提高一氧化氮供体型杂合物的生物活性。这些有趣的结果可以为基于一氧化氮的抗白血病药物的开发提供新的思路。
