双环克拉霉素衍生物的合成及抗肿瘤活性研究  

Synthesis and antitumor activity study of bicyclic clarithromycin derivatives

作　　者：孙俊[1,2] 王展[2,3] 潘佳彤[2] 关奇 张为革[2] 吴岚[4] SUN Jun;WANG Zhan;PAN Jiatong;GUAN Qi;ZHANG Weige;WU Lan(Pharmaceutical Department of Henan Provincial People′s Hospital,Zhengzhou 450003,China;School of Pharmaceutical Engineering,Shenyang Pharmaceutical University,Shenyang 110016,China;Pharmaceutical Department,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China;Department of Geratology,the First Affiliated Hospital,Chinese Medical University,Shenyang 110001,China)

机构地区：[1]河南省人民医院药学部,河南郑州450003 [2]沈阳药科大学制药工程学院,辽宁沈阳110016 [3]郑州大学第一附属医院药学部,河南郑州450052 [4]中国医科大学附属第一医院老年医学科,辽宁沈阳110001

出　　处：《沈阳药科大学学报》2024年第1期79-85,共7页Journal of Shenyang Pharmaceutical University

基　　金：河南省科技攻关项目(222102310126);沈阳市科技计划项目公共卫生科技专项项目(20-205-4-026)。

摘　　要：目的设计并合成一系列3-氧代-8,9;10,11-双脱水-N-去甲克拉霉素衍生物,进行体外抗肿瘤活性研究。方法以克拉霉素为起始原料,经脱除克拉定糖、羟基保护、氧化、脱除羟基保护基、去甲基化、酰化反应得到目标化合物。采用MTT法测定目标化合物对人纤维肉瘤细胞株HT1080、人口腔癌细胞株KB和人胃癌细胞株SGC-7901的增殖抑制活性。结果合成了10个结构新颖的双环克拉霉素衍生物,其结构经13C-NMR和HR-MS确证;其中,化合物12f和12g具有良好的抗肿瘤活性。结论合成的双环克拉霉素衍生物具有一定的抗肿瘤活性,为抗肿瘤创新药物研究提供了新思路。Objective To synthesize a series of 3-oxo-8,9;10,11-dianhydro-N-demethyl-clarithromycin derivatives and to evaluate their antiproliferative activities.Methods With clarithromycin as the starting material,target compounds were prepared by removing cladinose,protection of hydroxyl,oxidation,deprotection of hydroxyl,demethylation,and acylation.All compounds were evaluated for their antiproliferative activities against three human cancer cell lines(HT-1080,KB and SGC-7901)by the MTT assay.Results Ten novel bicyclic clarithromycin derivatives were synthesized and characterized by ^(13)C-NMR and HRMS.Among them,12f and 12g showed the best antitumor activities.Conclusion The bicyclic clarithromycin derivatives have certain antitumor activity,which provides a new idea for the research of innovative antitumor drugs.

关 键 词：克拉霉素衍生物 合成 抗肿瘤活性 

分 类 号：R914[医药卫生—药物化学]