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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 the B ring modified derivatives of desmosdumotin-C and study its anti-tumor activity in vitro. Methods The 2,4-trihydroxyacetophenone was used as the starting material to obtain the polyalkyl substituted A ring by the two steps of benzene ring alkylation and 4-O-alkylation. The aldehyde benzene Formic acid as raw material, the B ring containing amino acid amide structure is prepared through Schotten-Baumann reaction, and finally the target compound is obtained by connecting A ring, B ring or arylaldehyde through Claisen-Schmidt reaction. The synthesized target compounds were evaluated for in vitro tumor cell proliferation inhibitory activity by the sulfo-rhodamine B method. Results Seventeen target compounds were synthesized and 12 of them were new compounds. Their structures were confirmed by MS and 1H-NMR. The antitumor activity of the target compounds in vitro showed that most of the compounds were superior or equivalent to desmosdumotin-C. Conclusions The antitumor activity of the compound desmosdumotin-C can be effectively improved by structural modification and modification of the precursor desmosdumotin-C, such as introduction of a long alkyl chain in the A ring, introduction of a halogen, amino acid amide structure in the B ring, and the like, as the subsequent desmosdumotin-C derivative Structural optimization provides direction and data support.