School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, Guangxi, China.
College of Pharmacy, Guilin Medical University, Guilin 541100, Guangxi, China.
Molecules. 2019 Nov 19;24(22):4191. doi: 10.3390/molecules24224191.
To discover novel potent cytotoxic diterpenoids, a series of hybrids of dehydroabietic acid containing 1,2,3-triazole moiety were designed and synthesized. The target compounds were characterized by means of FT-IR, H NMR, C NMR, ESI-MS and elemental analysis techniques. The in vitro cytotoxicity of these compounds was evaluated by standard MTT (methyl thiazolytetrazolium) assay against CNE-2 (nasopharynx), HepG2 (liver), HeLa (epithelial cervical), BEL-7402 (liver) human carcinoma cell lines and human normal liver cell (HL-7702). The screening results revealed that most of the hybrids showed significantly improved cytotoxicity over parent compound DHAA. Among them, [1-(3-fluorobenzyl)-1-1,2,3-triazole-4-yl]dehydroabietic acid methyl ester (), and [1-(2-nitrobenzyl)-1-1,2,3-triazole-4-yl]dehydroabietic acid methyl ester () displayed better antiproliferative activity with IC (50% inhibitory concentration) values of 5.90 ± 0.41 and 6.25 ± 0.37 µM toward HepG2 cells compared to cisplatin, while they exhibited lower cytotoxicity against HL-7702. Therefore, the 1,2,3-triazole-hybrids could be a promising strategy for the synthesis of antitumor diterpenoids and it also proved the essential role of 1,2,3-triazole moiety of DHAA in the biological activity.
为了发现新型有效的细胞毒性二萜类化合物，设计并合成了一系列含 1,2,3-三唑部分的脱氢松香酸的杂合体。目标化合物通过傅里叶变换红外光谱（FT-IR）、核磁共振氢谱（1H NMR）、核磁共振碳谱（13C NMR）、电喷雾质谱（ESI-MS）和元素分析技术进行了表征。通过标准 MTT（噻唑蓝）法对这些化合物在 CNE-2（鼻咽）、HepG2（肝）、HeLa（上皮宫颈）、BEL-7402（肝）人癌细胞系和人正常肝细胞（HL-7702）中的体外细胞毒性进行了评估。筛选结果表明，大多数杂合体的细胞毒性均明显优于母体化合物 DHAA。其中，[1-(3-氟苄基)-1-1,2,3-三唑-4-基]脱氢松香酸甲酯（）和[1-(2-硝基苄基)-1-1,2,3-三唑-4-基]脱氢松香酸甲酯（）对 HepG2 细胞的增殖活性具有更好的抑制作用，其 IC（50%抑制浓度）值分别为 5.90 ± 0.41 和 6.25 ± 0.37 μM，优于顺铂，而对 HL-7702 的细胞毒性较低。因此，1,2,3-三唑杂合体可能是合成抗肿瘤二萜类化合物的有前途的策略，也证明了 DHAA 中 1,2,3-三唑部分在生物活性中的重要作用。
