Department of Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Yokohama 223-8522, Japan.
Bioorg Med Chem Lett. 2013 Mar 1;23(5):1467-71. doi: 10.1016/j.bmcl.2012.12.052. Epub 2012 Dec 25.
Aplyronine A (1) and mycalolide B (2), which are cytotoxic actin-depolymerizing marine macrolides, were revealed to induce apoptosis in human leukemia HL60 cells and human epithelial carcinoma HeLa S(3) cells. Based on these results, actin-depolymerizing compounds were expected to exhibit apoptosis-inducing activity in cancer cells. Compounds 3-6, which were synthesized based on the side-chain structure of aplyronine A, were evaluated for their actin-depolymerizing activities in vitro and cytotoxicities against HL60 cells. The growth-inhibitory activities of 3-6 were well correlated with their actin-depolymerizing activities, and derivative 6 was shown to induce the disruption of actin filaments and apoptosis in HL60 cells. These results suggested that actin-depolymerizing agents 1, 2, and 6-induced apoptosis in HL60 cells may have been due to their actin-depolymerizing activity.
阿朴隆宁 A（1）和麦角甾内酯 B（2）是具有细胞毒性的解聚肌动蛋白海洋大环内酯类化合物，已被证明可诱导人白血病 HL60 细胞和人上皮癌细胞 HeLa S（3）细胞凋亡。基于这些结果，预计具有解聚肌动蛋白作用的化合物在癌细胞中具有诱导细胞凋亡的活性。基于阿朴隆宁 A 的侧链结构合成的化合物 3-6 被评估其体外的解聚肌动蛋白活性和对 HL60 细胞的细胞毒性。3-6 的生长抑制活性与其解聚肌动蛋白活性密切相关，衍生物 6 被证明可诱导 HL60 细胞中肌动蛋白丝的破坏和细胞凋亡。这些结果表明，HL60 细胞中解聚肌动蛋白剂 1、2 和 6 诱导的细胞凋亡可能与其解聚肌动蛋白活性有关。
