【摘要】 从线叶唇柱苣苔全草中首次分离和鉴定了6个蒽醌（1、2、3、5、8、9）、2个α-董尼酮（4、7）和1个萘骈董尼酮（6）。抗癌研究表明,羟甲基取代能显著拓宽蒽醌的抗癌谱,晚期凋亡作用强度与蒽醌母核上酚羟基数成正相关。α-董尼酮母核7位酚羟基的取代（4）可显著扩大其抗癌谱和提高抗癌效果（对所选所有癌株抑制率均接近100%）,而该酚羟基甲氧基化后（7）抗癌谱变窄、活性显著降低。α-董尼酮（4）既没有晚期凋亡作用也没有基于Caspase 3/PARP的抗癌途径,而其萘骈董尼酮同系物（6）对乳腺癌（MCF-7）具有高效拮抗(IC₅₀=0.53μM,强度为顺铂18.3倍)、显著的晚期凋亡作用和基于PARP的抗癌途径。蒽醌（5、9）和α-董尼酮（4）对PARP均无切割诱导作用,而萘骈董尼酮（6）具有显著的PARP切割诱导活性。可见,α-董尼酮抗癌谱广,为良好的抗癌先导成分;萘骈董尼酮具有研制为新型靶向抗癌PARP抑制剂的潜力。更多还原

【Abstract】 Six anthraquinones（ 1,2,3,5,8,9）,two α-dunniones（ 4,7） and a naphthodunnione（ 6） were firstly isolated from the whole herb of Chirita linearifolia W. T. Wang,and their structures were elucidated. In anticancer investigations,the substitution of methylol group on anthraquinone core obviously broadened the anticancer spectrum and the numbers of Ph-OH on anthraquinone core correlated positively with the intensity of late-stage-apoptosis.The substituted Ph-OH at 7-position of α-dunnione core（ 4） not only broadened its anticancer spectrum but also improved its anticancer intensity（ the anticancer inhibition percent of 4 to all tested cancer cell lines were nearly 100%）,while,both anticancer spectrum and anticancer intensity were seriously reduced after above Ph-OH being substituted by OCH₃（ 7）. α-Dunnione（ 4） showed neither late-stage-apoptosis nor Caspase 3/PARP pathway,while,naphthodunnione（ 6） manifested very high antagonism against breast cancer cell line（ MCF-7） with IC₅₀ of 0. 53 μM（ which was18. 3 times to that of cisplatin）,remarkable late-stage-apoptosis and PARP anticancer pathway.Neither anthraquinones（ 5,9） nor α-dunnione（ 4） had PARP cleaving induction,while,naphthodunnione（ 6） owned significant PARP cleaving induction. To sum up,α-dunnione with broad anticancer spectrum was an excellent anticancer lead compound,and naphthodunnione had potentiality to develop into new targeted-anticancer-PARP-inhibitors.更多还原