Desmosdumotin-C B环氨基酸酰胺修饰衍生物的合成与抗肿瘤活性评价  

Synthesis of Amino Acid Amide Modified Desmosdumotin C Derivatives on B-ring and Antitumor Activity Evaluation

作　　者：梁海[1,2] 向卓[2,3] 郭宏举 厉恩振[2] 史宁[2] 张学辉[2] 吴久鸿[2] 

机构地区：[1]安徽医科大学药学院,合肥230032 [2]解放军第306医院药学部,北京100101 [3]第四军医大学药学院,西安710032

出　　处：《中国药学杂志》2014年第23期2128-2135,共8页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金资助课题(81072546;81470156)

摘　　要：目的设计、合成desmosdumotin-C的B环修饰衍生物,并考察其体外抗肿瘤活性。方法以2,4,6-三羟基苯乙酮为起始原料,经苯环烷基化、4-O-烷基化2步反应制得多烷基取代的A环;以对醛基苯甲酸为原料,经Schotten-Baumannn反应制得含有氨基酸酰胺结构的B环;最后通过Claisen-Schmidt反应连接A环和B环或芳醛制得目标化合物。通过磺基罗丹明B法对所合成的目标化合物进行体外肿瘤细胞增殖抑制活性评价。结果制备合成了17个目标化合物,其中12个为新化合物,其结构经MS,1H-NMR确证;目标化合物体外抗肿瘤活性表明,大部分化合物的活性优于或相当于desmosdumotin-C。结论通过对先导物desmosdumotin-C进行结构修饰和改造可有效提高化合物的抗肿瘤活性,如在A环引入长烷基链,在B环引入卤素、氨基酸酰胺结构等,为后续desmosdumotin-C衍生物的结构优化提供方向和数据支持。OBJECTIVE To design and synthesize desmosdumotin C derivatives on B-ring and investigate their antitumor aetivities in vitro, METHODS The A-ring of the target compounds was firstly synthesized from 2,4,6-trihydroxyacetophenone by alkylation and 4-O-alkylation. Then the B-ring was synthesized by the Sehotten-Baumannn reaction. Finally, the derivatives of desmosdumotin C with amide-linked substituents or aromatic aldehydes on B-ring were synthesized by the Claisen-Schmidt reaction. The antitumor activities of the compounds were evaluated by SRB assay. RESULTS Seventeen target compounds were synthesized, 12 of which were new compounds. All of them were confirmed by ^1 H-NMR and MS spectra. Preliminary pharmacological test showed that most of the compounds had equal or better antitumor activities than deslnosdumotin C in vitro. CONCLUSION The structural modifications of desmosdumotin C would significantly increase the antitumor activity of the compounds, such as long alkyl chain substituted Ring A, amino acid amides on B-ring and so on, which provides the basis for the structure optimization of desmosdumotin C derivatives.

关 键 词：Desmosdumotin-C 衍生物 氨基酸酰胺修饰 合成 抗肿瘤 

分 类 号：R914[医药卫生—药物化学]