Yao Guo-Dong, Cheng Zhuo-Yang, Shang Xin-Yue, Gao Pin-Yi, Huang Xiao-Xiao, Song Shao-Jiang
a School of Traditional Chinese Materia Medica , Shenyang Pharmaceutical University , Shenyang 110016 , China.
b Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education , Shenyang Pharmaceutical University , Shenyang 110016 , China.
J Asian Nat Prod Res. 2017 Nov;19(11):1134-1142. doi: 10.1080/10286020.2017.1292256. Epub 2017 Feb 19.
Hepatocellular carcinoma (HCC), the most common type of liver cancer, has high morbidity and mortality rates, and its prognosis is poor. The treatment options of HCC are limited by the lack of effective chemotherapy. Therefore, looking for effective drugs with little toxicity is very urgent. The aim of this study was to search for small molecule targeting on liver cancer from Juglans mandshurica, which has been used to treat cancers for a long time in China. Under the guide of anti-hepatoma activity, a new coumarin (1), together with eight reported analogs (2‒9), was isolated from the 75% EtOH extract. The structures of these compounds were determined by 1D and 2D NMR experiments. The absolute configuration of 1 was established by comparison of experimental and calculated electronic circular dichroism (ECD) spectra. The in vitro cytotoxicity experiments on two liver cancer cell lines (HepG2 and Hep3B) showed that compounds 2 and 5 had moderate antitumor activities on both cell lines. And further studies of antitumor mechanisms by the observation of morphological changes and Western blot analyses exhibited that induction of apoptosis might be a possible way that inhibited cell growth.
肝细胞癌(HCC)是最常见的肝癌类型,其发病率和死亡率都很高,预后较差。HCC的治疗选择因缺乏有效的化疗而受到限制。因此,寻找毒性小的有效药物迫在眉睫。本研究的目的是从中国长期用于治疗癌症的胡桃楸中寻找靶向肝癌的小分子。在抗肝癌活性的指导下,从75%乙醇提取物中分离出一种新的香豆素(1)以及八个已报道的类似物(2-9)。这些化合物的结构通过一维和二维核磁共振实验确定。通过比较实验和计算的电子圆二色光谱(ECD)确定了1的绝对构型。对两种肝癌细胞系(HepG2和Hep3B)进行的体外细胞毒性实验表明,化合物2和5对两种细胞系都有中等程度的抗肿瘤活性。通过观察形态变化和蛋白质印迹分析对抗肿瘤机制的进一步研究表明,诱导凋亡可能是抑制细胞生长的一种可能方式。