含酰肼基磺酰胺片段新型化合物的合成及体外抗肿瘤活性研究  

Synthesis of novel compounds containing acylhydrazyl sulfonamide moiety and their study of antitumor activity in vitro

作　　者：李芳耀[1,2,3,4] 庞富华 马献力[1,2,3,4] LI Fangyao;PANG Fuhua;MA Xianli(College of Pharmacy,Guilin Medical University,Guilin 541199,China;Guangxi Key Laboratory of Drug Discovery and Optimization,Guilin Medical University,Guilin 541199,China;Guangxi Engineering Research Center for Pharmaceutical Molecular Screening and Drug Property Evaluation,Guilin Medical University,Guilin 541199,China;Key Laboratory of Medical Biotechnology and Translationl Medicine,Guilin Medical University,Guilin 541199,China)

机构地区：[1]桂林医学院药学院,广西桂林541199 [2]桂林医学院广西药物分子发现与成药性优化重点实验室,广西桂林541199 [3]桂林医学院广西药物分子筛选与成药性评价工程研究中心,广西桂林541199 [4]桂林医学院广西高校医药生物技术与转化医学重点实验室,广西桂林541199

出　　处：《华夏医学》2023年第4期1-12,共12页Acta Medicinae Sinica

基　　金：国家自然科学基金项目(82160657);广西自然科学基金项目(2022JJA130349);桂林市科学研究与技术开发计划项目(20210227-1);广西林产化学与工程重点实验室开放课题资助项目(GXFK2202);广西高等学校千名中青年骨干教师培育计划资助项目(桂教师范〔2019〕81号)。

摘　　要：目的:对松香进行化学结构修饰,寻找新型抗肿瘤活性化合物。方法:以去氢枞酸为原料,经三步反应合成得到N-(酰肼基磺酰基)-4-去氢枞醇氨基甲酸酯类化合物,利用^(1 )H NMR、^(13 )C NMR、ESI-MS和FT-IR等方法对产物结构进行表征。以5-氟尿嘧啶作阳性对照,评价化合物对T-24、HepG2、MCF-7、MGC-803和Hela等5种肿瘤细胞株的体外抗肿瘤活性。结果:合成15个新型N-(酰肼基磺酰基)-4-去氢枞醇氨基甲酸酯类化合物,体外抗肿瘤实验结果表明,大部分化合物对这5种癌细胞具有中等的活性,部分化合物的细胞毒性优于阳性药物。结论:引入酰肼基磺酰胺结构片段,可提高母体化合物的细胞毒性,目标化合物对人乳腺癌细胞和人胃癌细胞的抑制活性相对较好,值得进一步研究。Objective:In order to search for novel antitumor compounds,the structure of rosin was modified.Methods:N-(hydrazyl sulfonyl)-4-dehydroabietinol carbamate compounds were synthesized from dehydroabietic acid via 3 step reactions and their structures were confirmed by ^(1)H NMR,^(13)C NMR,ESIMS and FT-IR.The in vitro antitumor activity against T-24,HepG2,MCF-7,MGC-803 and Hela tumor cell lines was evaluated using 5-fluorouracil as positive control.Results:Fifteen novel N-(hydrazyl sulfonyl)-4-dehydroabietinol carbamate compounds were synthesized.In vitro cytotoxicity assay results showed that most of the compounds with moderate levels of activity against these five cancer cell lines,and some displayed more cytotoxic than positive drugs.Conclusion:The introduction of structural fragments of acylhydrazine sulfonamide can improve the cytotoxicity of the parent compound.And the target compounds has showed relatively better inhibitory activity against MCF-7 and MGC-803 tumor cell lines,which is worthy of further study.

关 键 词：去氢枞酸 去氢枞醇 氨基甲酸酯 抗肿瘤活性 

分 类 号：R914[医药卫生—药物化学]