Advanced Life Sciences, Inc., 1440 Davey Road, Woodridge, IL 60517, United States.
Bioorg Med Chem Lett. 2010 Sep 15;20(18):5389-93. doi: 10.1016/j.bmcl.2010.07.120. Epub 2010 Aug 3.
Apoptosis is a highly regulated process by which excessive cells are eliminated in order to maintain normal cell development and tissue homeostasis. Resistance to apoptosis often contributes to failure in cancer prevention and treatment. Apoptotic cell death regulators are considered important targets for discovery and development of new therapeutic agents in oncology research. A class of novel aza-lupane triterpenoids were designed, synthesized, and evaluated for antitumor activity against a panel of cancer cell lines of different histogenic origin and for ability to induce apoptosis. 3,30-Bis(aza) derivatives were identified not only to possess improved cytotoxicity compared to the natural product betulinic acid but also to affect cell death predominantly via apoptosis, whereas the mono(aza) derivatives apparently triggered cell death via different, non-apoptotic pathway(s).
细胞凋亡是一种高度调控的过程，通过该过程可以消除过多的细胞，以维持正常的细胞发育和组织平衡。细胞凋亡的抵抗常常导致癌症预防和治疗的失败。凋亡细胞死亡调节剂被认为是肿瘤学研究中发现和开发新型治疗药物的重要靶标。设计、合成了一类新型的氮杂升麻烷三萜类化合物，并对其进行了抗肿瘤活性评价，这些化合物针对不同组织来源的一组癌细胞系，以及诱导细胞凋亡的能力。结果表明，3,30-双（氮杂）衍生物不仅具有比天然产物白桦脂酸更高的细胞毒性，而且还能主要通过细胞凋亡影响细胞死亡，而单（氮杂）衍生物显然通过不同的、非细胞凋亡途径触发细胞死亡。
