新型吡唑并[3,4-b]吡啶-4-酮-5-羧酸类化合物的合成及抗菌抗肿瘤活性  

Design,synthesis,antibacterial and antitumor activities of novel pyrazolo[3,4-b]pyridine-4-one-5-carboxylic acid derivatives

作　　者：李阳杰 李珂 胡国强[2] 黄文龙[3] LI Yang-jie;LI Ke;HU Guo-qiang;HUANG Wen-long(Henan Engineering Technology Research Center of Water Environment and Health,Zhengzhou University of Industrial Technology,Zhengzhou 451150,China;School of Clinical Medicine,Henan University,Kaifeng 475004,China;Center of Drug Discovery,China Pharmaceutical University,Nanjing 210009,China)

机构地区：[1]郑州工业应用技术学院,河南省水环境与健康河南省工程技术研究中心,河南郑州451150 [2]河南大学临床医学院,河南开封475004 [3]中国药科大学新药中心,江苏南京210009

出　　处：《药学学报》2023年第10期3070-3075,共6页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(20872028,21072045)。

摘　　要：为发现新结构苗头化合物,基于吡唑与吡啶酮酸片段在药物分子中的重要性,设计合成了一系列吡唑并[3,4-b]吡啶-4-酮-5-羧酸类新结构目标化合物(10a~10p),其结构经光谱数据和元素分析确证。目标化合物体外对4种实验菌株显示出较弱的抗菌活性或抗菌活性消失,而对4种癌细胞株的抗肿瘤活性强于对照氟喹诺酮药,尤其是双-氟苯基(10d、10e、10f)、吡啶基(10j)、乙基(10k)和环丙(10l)等取代化合物对Capan-1和A549细胞株的IC_(50)值达到微摩尔浓度。为此,吡唑并吡啶-4-酮-5-羧酸类化合物虽然抗菌活性不及氟喹诺酮类,而其抗肿瘤活性显著强于对照氟喹诺酮药,其中部分化合物抗肿瘤活性与多柔比星活性相当,预示可作为新结构抗肿瘤苗头化合物值得进一步发展。To discover new structural hits,based on the important role of pyrazole ring and fragment of pyridinone carboxylic acid in drug design,novel title pyrazolo[3,4-b]pyridine-4-one-5-carboxylic acid derivatives(10a-10p)were designed and synthesized,the structures were confirmed by spectral data and elemental analyses.The antibacterial and antitumor activities were evaluated by the measured minimum inhibitory concentration(MIC)values against the tested four strains and half inhibitory concentration(IC_(50))values against the tested four cancer cells,respectively.The results displayed markedly poor antibacterial activity and observably potent antitumor activity.In particularly,the title difluorophenyl(10d,10e,10f),pyridyl(10j),ethyl(10k)and cycloproyl(101)compounds exhibited comparable activity against Capan-1 and A549 cells to that of the comparison doxorubicin.Thus,pyrazolo[3,4-b]pyridine-4-one-5-carboxylic acid derivatives as promising antitumor hits need to be developed.

关 键 词：吡唑 吡啶酮羧 吡唑并吡啶酮羧 抗菌活性 抗肿瘤活性 

分 类 号：R914[医药卫生—药物化学]