| 候欣鲁,贾耿,李忠强,等.新型乌苯美司-吉西他滨偶联物的合成与抗肿瘤活性研究（英文）[J].中国海洋药物,2026,(2):-. |
| 新型乌苯美司-吉西他滨偶联物的合成与抗肿瘤活性研究（英文） |
| Synthesis and anti-cancer evaluation of the novel Ubenimex-Gemcitabine conjugates |
| 投稿时间：2025-01-13 修订日期：2025-04-02 |
| DOI： |
| 中文关键词: 海洋来源核苷类似物 乌苯美司-吉西他滨偶联物 CD13 抗肿瘤 |
| English Keywords:marine-derived nucleoside analogues ubenimex-gemcitabine conjugates CD13 antitumor |
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| 中文摘要: |
| 海洋生态系统促进了阿糖胞苷及其氟化衍生物吉西他滨（GEM）的发现。吉西他滨临床上广泛用于多种癌症的治疗。在前期研究中，本课题组发现了一种乌苯美司-吉西他滨偶联物BC-A1，其体内抗肿瘤疗效显著。然而，BC-A1对氨肽酶N（APN/CD13） 的抑制活性仍有待提高。本研究以BC-A1为结构基础，通过优化乌苯美司和吉西他滨之间的连接链，设计并合成了5个新型乌苯美司-吉西他滨偶联物。代表性化合物1对CD13的抑制活性比乌苯美司和BC-A1高出约10倍。此外，化合物1的体外抗增殖活性优于或与BC-A1和吉西他滨相当。化合物1可作为先导化合物，用于进一步设计开发新型的抗肿瘤药物。 |
| English Summary: |
| The marine ecosystem that facilitated the discovery of cytarabine and its fluorinated derivative, gemcitabine (GEM). Gemcitabine was used to treat various cancers. In our previous study, our group identified an ubenimex-gemcitabine conjugate, BC-A1, with notable in vivo antitumor efficacy. However, the inhibitory activity of BC-A1 on aminopeptidase N (APN/CD13) remains to be enhanced. Herein, five novel ubenimex-GEM conjugates were designed and synthesized by optimizing the linkers between ubenimex and gemcitabine based on BC-A1.. The representative compound 1 exhibited approximately a 10-fold higher inhibitory activity against CD13 than ubenimex and BC-A1. Additionally, the in vitro anti-proliferative activity of compound 1 was better or comparable to that of BC-A1 and gemcitabine. Compound 1 can be used as a lead compound for further design to develop novel antitumor drugs. |
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