异长叶烷基-喹唑啉-2-胺衍生物的合成与生物活性评价

Synthesis and Biological Evaluation of Isolongifolanyl-quinazolin-2-amine Derivatives

摘要:

以异长叶烷酮为原料，经缩合，环化等反应合成出6个喹唑啉-2-胺衍生物(Ⅲa~Ⅲf)。采用1HNMR、13CNMR、IR、HRMS等对其结构进行了表征。采用MTT法考察了化合物Ⅲ a~Ⅲf对人肝癌细胞(HepG2)和人脐静脉内皮细胞(HUVECs)的抑制活性。结果表明，化合物Ⅲa、Ⅲb、Ⅲd、Ⅲf〔半抑制浓度(IC50)分别为8.58±0.5、44.52±0.9、57.18±0.8、32.83±0.6 μmol/L〕对HepG2有一定的抗肿瘤活性。其中，4-(4'-氯苯基)-6,6,10,10-四甲基-5,6,6a,7,8,9,10,10a-八氢-6a,9-甲基苯并[h]喹唑啉-2-胺(Ⅲa)抗HepG2的活性最强；只有4-[4'–(二甲基氨基)苯基]-6,6,10,10-四甲基-5,6,6a,7,8,9,10,10a-八氢-6a,9-甲基苯并[h]喹唑啉-2-胺(Ⅲf)对HUVECs有抑制活性。同时，采用叶浸渍法考察了化合物Ⅲa~Ⅲf对桃蚜的杀虫活性，结果表明，化合物Ⅲa、Ⅲd 〔致死中浓度（LC50）=37.4589±6.412, 41.0073±5.920 mg/L〕对桃蚜具有较好的杀虫活性。

Abstract:

A series of quinazolin-2-amine derivatives (Ⅲa~Ⅲf) were synthesized by condensation, cyclization and so on from isolongifolanone and characterized by 1HNMR, 13C NMR, IR and HRMS. Their inhibitory activity against human hepatoma cell (HepG2) and human umbilical vein endothelial cells (HUVECs) were evaluated by MTT assay. The results showed that the half maximal inhibitory concentrations of compounds Ⅲa, Ⅲb, Ⅲd and Ⅲf were 8.58±0.5, 44.52±0.9, 57.18±0.8 and 32.83±0.6 μmol/L, indicating that these compounds showed moderate antitumor activity against HepG2. Among these compounds, compound Ⅲa, 4-(4'-chlorophenyl)-6,6,10,10-tetramethyl-5,6,6a,7,8,9,10,10a-octahydro-6a,9-methanobenzo[h]quinazolin-2-amine, had the best activity against HepG2. Only 4-(4'-(N,N-dimethylamino)phenyl)-6,6,10,10-tetramethyl-5,6,6a,7,8,9,10,10a-octahydro-6a,9-methanobenzo[h]quinazolin-2-amine (Ⅲf) showed a certain inhibitory activity against HUVECs. These compounds were also carried out to evaluate against myzus persicae by a leaf-dipping method. It was found that compounds Ⅲa and Ⅲd gave excellent insecticidal activity against myzus persicae with corresponding lethal concentration (LC50) of 37.4589±6.412 and 41.0073±5.920 mg/L.