A new series of CA4P analogs (5a-g, 6a-g) has been designed and effectively synthesized via a one-pot reaction from Combretastatin A-4/Erianin, commercially available amino acid esters and phenyl dichlorophosphate. To establish new candidates with anticancer activity, the in vitro antiproliferative effect of these compounds was measured by the CCK8 method on different cancer cell lines such as human liver caricinoma (HepG2), cervical cancer (HeLa) and colorectal carcinoma (HCT-116). The structure-activity relationships between CA4P outgrowth-promoting activity and its analogs suggested that the biaryl structure linked with double bond in Part A and the steric effect at the position α-carbon atom in the amino acid ester moiety (Part B) are essential for affecting the in vitro proliferation inhibitory activity of CA4P analogs. Additionally, the results of biological activity and molecular docking simulation showed that the vast majority of these novel Phosphoramidate derivatives exhibited potent anti-cancer activities.

通过Combretastatin A-4 / Erianin，市售氨基酸酯和苯基二氯磷酸酯的一锅反应，设计并有效合成了一系列新的CA4P类似物（5a-g，6a-g）。为了建立具有抗癌活性的新候选物，通过CCK8方法测量了这些化合物对不同癌细胞系（例如人肝癌（HepG2），宫颈癌（HeLa）和结直肠癌（HCT-116））的体外抗增殖作用。CA4P增生活性与其类似物之间的构效关系表明，A部分中的双芳基结构与双键相连，α位处的空间效应氨基酸酯部分（B部分）中的-碳原子对于影响CA4P类似物的体外增殖抑制活性至关重要。此外，生物学活性和分子对接模拟的结果表明，这些新型磷酰胺酯衍生物中的绝大多数表现出有效的抗癌活性。