Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Hôpital Kirchberg, 9 Rue Edward Steichen, L-2540 Luxembourg, Luxembourg.
Bioorg Med Chem. 2013 Jul 1;21(13):3850-8. doi: 10.1016/j.bmc.2013.04.024. Epub 2013 Apr 22.
Altersolanol A, a natural product from the endophytic fungus Stemphylium globuliferum isolated from the medicinal plant Mentha pulegium (Lamiaceae) growing in Morocco, shows cytotoxic, cytostatic, anti-inflammatory and anti-migrative activity against human chronic myeloid K562 leukemia and A549 lung cancer cells in a dose dependent manner without affecting the viability of non cancerous cells. Altersolanol A induces cell death by apoptosis through the cleavage of caspase-3 and -9 and through the decrease of anti-apoptotic protein expression. Moreover, we report here the importance of the distinct structural features of altersolanol A by testing other related anthracene derivatives in order to identify preliminary structure-activity relationships. Acetylation of altersolanol A did not improve activity where other derivatives such as tetrahydroaltersolanol B and ampelanol that differ from altersolanol A by reduction of one of a carbonyl group and removal of hydroxyl substituents were inactive in comparison. Altogether our results suggest that altersolanol A may be considered as an interesting lead for further development of chemotherapeutic agents.
从生长在摩洛哥的唇形科薄荷属植物皱叶留兰香内生真菌中分离出的天然产物阿尔特索尔醇 A 对人类慢性髓性白血病 K562 细胞和肺癌 A549 细胞具有细胞毒性、细胞生长抑制、抗炎和抗迁移活性,并呈剂量依赖性,而对非癌细胞的活力没有影响。阿尔特索尔醇 A 通过半胱天冬酶-3 和 -9 的裂解和抗凋亡蛋白表达的降低诱导细胞凋亡。此外,我们通过测试其他相关蒽衍生物来报告阿尔特索尔醇 A 的不同结构特征的重要性,以确定初步的结构-活性关系。阿尔特索尔醇 A 的乙酰化没有提高活性,而其他衍生物,如四氢阿尔特索尔醇 B 和ampelanol,与阿尔特索尔醇 A 不同,它们通过减少一个羰基和去除羟基取代基而失活。总之,我们的结果表明,阿尔特索尔醇 A 可被视为进一步开发化疗药物的一个有趣的先导化合物。