新型苦参碱C-14腙类衍生物的合成及抗肿瘤活性研究

Synthesis and Antitumor Activity of Novel Matrine C-14 Hydrazone Derivatives

以苦参碱为先导化合物,设计并合成了16个苦参碱腙类衍生物,均采用^(1)HNMR、^(13)CNMR和HR-MS进行了结构表征。通过MTT比色法进行体外抗增殖活性实验,测试了所有目标化合物对人宫颈癌细胞HeLa、人结肠癌细胞HCT116和非小细胞肺癌细胞A549的活性,部分目标化合物表现出比苦参碱更为优越的抗增殖活性,尤其是化合物14-(((4-叔丁基苄基)-^(1)H-吲哚-3-亚甲基)肼亚甲基)苦参碱,其对HeLa、HCT116和A549细胞的IC_(50)值分别为(11.65±0.28)、(9.14±0.81)和(14.48±0.63)μmol/L,在3种细胞中显示出卓越的抗增殖活性,尤其对HCT116细胞的抗增殖活性最强。进一步的细胞周期实验结果显示,目标化合物能够阻滞HCT116细胞在G0/G1期。分子对接结果表明,该化合物与蛋白6QJX存在氢键和π-π堆积作用等相互作用力。

Designed and synthesized sixteen matrine hydrazone derivatives with matrine as the lead compound.The structures of all compounds were characterized using^(1)HNMR,^(13)CNMR,and HR-MS analyses.The anti-proliferative activities of these compounds were evaluted on three cell lines:human cervical cancer cell HeLa,human colon cancer cell HCT116 and non-small cell lung cancer cell A549,through MTT colorimetric assay in vitro.Several derivatives exhibited notable anti-proliferative activities against the aforementioned cell lines,surpassing the efficacy of matrine.The most potent compound 14-(((4-tert-butylbenzyl)-1h-indole-3-methylene)hydrazine methylene)matrine,demonstrated IC_(50) values of(11.65±0.28),(9.14±0.81),and(14.48±0.63)μmol/L against HeLa,HCT116,and A549 cells,respectively,with the highest anti-proliferative activity observed against HCT116 cells.Results from cell cycle experiments revealed that this compound blocked HCT116 cell cycle in G0/G1 phase.Molecular docking analysis indicated the presence of interaction forces,including hydrogen bonding andπ-πstacking,between target compound and protein 6QJX.