Oncrasin-1类衍生物的合成及其抗肿瘤活性初探

Synthesis and Antitumor Activity of Oncrasin-1 Derivatives

Oncrasin-1类衍生物对来自肺癌、结肠癌等多种癌细胞系都具有高度活性,其中NSC-743380活性最佳。然而,它在结构上存在问题,易形成二聚体而失活,限制了进一步的研究发展。因此,本文以Oncrasin-1为先导化合物,设计了13种衍生物,通过引入氨基和酰胺基,尝试提高化合物稳定性并保留活性。化合物结构经1 H NMR,13 C NMR,HR-MS(ESI)表征,并通过细胞增殖实验(CCK-8实验)测定其对人胰腺癌细胞(PANC-1)、人宫颈癌细胞(HeLa)和人肝癌细胞(HepG2)的抗肿瘤活性。结果表明,13个Oncrasin-1类衍生物中,有10个表现出更好的活性,其中化合物4((4-(((1-(4-氯苄基)-1 H-吲哚-3-基)甲基)氨基)丁基)氨基甲酸叔丁酯)对HeLa的IC 50达到了3.98μM。

Derivatives of Oncrasin-1 are highly active against a variety of cancer cell lines,including those from lung and colon cancers.Among them,NSC-743380 has the best activity.However,it is suffering from structural problems in that it tends to form dimers and become inactivated,limiting further research development.Therefore,we designed to take Ocrasin-1 as a lead compound and synthesized thirteen derivatives.The amino and amide groups were introduced in an attempt to improve the stability and retain the activity of the compounds,and the structures were characterised by 1 H NMR,13 C NMR,HR-MS(ESI).The antitumor activity against human pancreatic cancer cells(PANC-1),human cervical cancer cells(HeLa)was also determined by CCK-8 assay.The results showed that ten of the thirteen derivatives showed better activity than Oncrasin-1,with compound 4(tert-butyl(4-(((1-(4-chlorobenzyl)-1 H-indol-3-yl)methyl)amino)butyl)carbamate)achieving an IC 50 of 3.98μM against HeLa.