引用本文:胡仕琴, 樊玲玲, 刘静姿, 何彬, 沈祥春, 廖尚高, 李勇军.新型杂环膦酸酯衍生物的合成与生物活性[J].西南大学学报(自然科学版),2019,41(8):64~73
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新型杂环膦酸酯衍生物的合成与生物活性
胡仕琴, 樊玲玲, 刘静姿, 何彬, 沈祥春, 廖尚高, 李勇军
贵州医科大学 药学院/贵州省药物制剂重点实验室/民族药与中药开发应用教育部工程研究中心, 贵阳 550004
摘要:
为了获得广谱、高效的活性先导物,我们在前期研究工作的基础上,结合药物设计原理,采用简便方法合成了一系列新型杂环膦酸酯衍生物,其结构经IR,(1H,13C,31P,19F)NMR和HRMS(ESI)等确证与表征.生物活性测试结果表明,部分化合物具有抗大肠杆菌、铜绿假单胞杆菌及金黄色葡萄球菌等活性,尤其是化合物A4,A8,A22,A24,A27和A28抗菌活性好,与对照药剂氨苄西林(Ampicillin)的MIC接近或相当.同时,发现部分化合物具有抑制肿瘤细胞增殖的作用,其中化合物A24和A28分别对人结肠癌细胞HT29和人肺癌细胞A549的IC50为18.0±0.7 μmol/L和17.1±1.3 μmol/L,接近对照药SAHA(IC50分别为14.3±1.1 μmol/L和12.5±1.8 μmol/L).在此基础上研究其构效关系,对进一步结构改造与优化具有十分重要的意义.
关键词:  杂环  膦酸酯  合成  抗菌活性  抗癌活性
DOI:10.13718/j.cnki.xdzk.2019.08.011
分类号:O626
基金项目:国家自然科学基金项目(81160385);贵州省科技厅项目(黔科合SY字[2012]3103);贵州省教育厅项目(黔省专合字[2012]89号);贵阳医学院基金项目(YJ2014-17).
Synthesis and Bioactivity of Novel Phosphate Derivatives Containing Heterocyclic Moieties
HU Shi-qin, FAN Ling-ling, LIU Jing-zi, HE Bin, SHEN Xiang-chun, LIAO Shang-gao, LI Yong-jun
School of Pharmacy, Guizhou Medical University/Provincial Key Laboratory of Pharmaceutics/Engineering Research Center for the Development and Application of Ethnic, Guizhou Medicine and TCM, Ministry of Education, Guiyang 550004, China
Abstract:
In order to obtain broad-spectrum and highly effective bioactivity lead compounds, a series of novel phosphonate derivatives containing heterocyclic moieties were synthesized with a simple method based on our preliminary research and combined with the drug design principle. Their structures were confirmed and characterized by IR, (1H, 13C, 31P and 19F) NMR and HRMS (ESI). A test of their bioactivity showed that some compounds had antibacterial activity against E. coli, P. aeruginosa, S. aureus and MRSA (Methicillin-resistant S. aureus) in some degree. Compounds A4, A8, A22, A24, A27 and A28 had a good antibacterial activity close or equal to that of the control agent Ampicillin. At the same time, it was found that compounds A24 and A28 had antitumor activity against tumor cell HT29 and human lung cancer cell A549, their IC50 being 18.0±0.7 μmol/L and 17.1±1.3 μmol/L, respectively, which was close to that of the control drug SAHA, whose IC50 was 14.3±1.1 μmol/L and 12.5±1.8 μmol/L, respectively. Further SAR (structure-activity relationship) studies based on our present results will be of significance for the structural modification and optimization of these compounds.
Key words:  heterocyclic  phosphonate  synthesis  antibacterial activity  antitumor activity
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