PP+-丝裂霉素C衍生物的设计、合成及抗肿瘤活性研究
esign, synthesis and biological evaluations of TPP+-Mitomycin C derivatives as antitumor agents
丝裂霉素C是一种临床上使用的抗恶性肿瘤药物，其非特异性DNA烷基化导致了严重的毒副作用。利用三苯基膦阳离子（TPP+）特异性靶向肿瘤细胞的特性构建了TPP+-丝裂霉素C靶向体系或将解决这一问题。以溴代羧酸和三苯基膦为原料合成TPP+羧酸盐，再与丝裂霉素C通过酰胺化反应得到3个全新的TPP+-丝裂霉素C衍生物d1-d3，结构经NMR确认。采用MTT法测定了衍生物的抗增殖活性，其中d2表现出较好的抗肿瘤活性和较低的毒性（IC50 = 1.09 ± 0.20 μM (A549)， IC50 > 10 μM (LO2)）。急性毒性试验进一步验证了其安全性。所有结果表明，TPP+-丝裂霉素C衍生物可以降低丝裂霉素C的毒性，具有进一步开发的潜力。
Mitomycin C is a clinically used anticancer drug, however, its non-specific DNA alkylation ability results in serious side effects. To address the issue, a triphenylphosphine cation (TPP+) that specifically target tumor cells was incorporated into Mitomycin C. In this paper, three novel TPP+-Mitomycin C derivatives (d1-d3) were synthesized by acylation of Mitomycin C with TPP+ carboxylate group, which was obtained from reactions of bromocarboxylic acids with triphenylphosphine. The antiproliferative activity of the derivatives was determined by a MTT assay, from which d2 showed a good antitumor activity and the most safety feature (IC50 = 1.09 ± 0.20 μM (A549), IC50 > 10 μM (LO2)). Furthermore, an acute toxicity experiment was conducted and verified its safety. Collectively, our results indicated that TPP+-Mitomycin C derivatives could reduce the toxicity of Mitomycin C and deserved for further development.
黄丁、张少林、贺耘
药学肿瘤学生物科学研究方法、生物科学研究技术
药物化学抗肿瘤丝裂霉素C线粒体靶向
medicinal chemistryantitumormitomycin cmitochondrial targeting
黄丁,张少林,贺耘.PP+-丝裂霉素C衍生物的设计、合成及抗肿瘤活性研究[EB/OL].(2022-03-03)[2025-09-05].http://www.paper.edu.cn/releasepaper/content/202203-36.点此复制
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