含NO供体的水杨酸卟啉酯类化合物的合成、体外活性及作用机制  

Synthesis,in Vitro Activity and Action Mechanism of Porphyrin Salicylate Analogs Containing NO Donors

作　　者：瑜文美 杨玲艳 刘振华 李辉 田泽杰 李嘉欣 易小婵 何军[2] 刘运美 YU Wen-mei;YANG Ling-yan;LIU Zhen-hua;LI Hui;TIAN Ze-jie;LI Jia-xin;YI Xiao-chan;HE Jun;LIU Yun-mei(School of Pharmacy,University of South China,Hengyang 421001,China;School of Chemistry and Chemical Engineering,University of South China,Hengyang 421001,China)

机构地区：[1]南华大学药学院,衡阳421001 [2]南华大学化学化工学院,衡阳421001

出　　处：《湖南师范大学自然科学学报》2023年第6期112-119,共8页Journal of Natural Science of Hunan Normal University

基　　金：湖南省研究生科研创新项目(CX20200954)。

摘　　要：设计并合成一系列新型含NO供体的水杨酸-卟啉化合物,并对其进行体外抗肿瘤活性评价,同时使用SYBYL软件初步探索卟啉-水杨酸化合物的作用机理。采用硝化、取代等方法得到含NO供体的水杨酸衍生物,再以酯键与卟啉相连得到一系列目标化合物。设计合成的20个未见报道的新型卟啉-水杨酸衍生物(7a-10e)均经1H NMR和MS进行了结构确证,利用MTT法评估了目标化合物分别在光照和黑暗条件下对HCT-116和A549的抑制效果,其中9b和9c在光照条件下对HCT-116细胞和A549细胞的增殖抑制作用较强,最后,分子对接实验表明目标化合物与CDK和PI3K具有良好的结合能力。A series of novel NO donor-containing salicylic acid-porphyrin compounds were designed and synthesized,and their in vitro anti-tumor activity was evaluated.Meanwhile,the corresponding action mechanism was initially explored using SYBYL software.Salicylic acid derivatives containing NO donors were obtained by nitration and substitution methods,and then a series of target compounds were obtained by ester bonding with porphyrins.Structures of all of the 20 obtained unreported porphyrin-salicylic acid derivatives(7a-10e)were confirmed by 1H NMR and MS.The inhibitory effects of the target compounds on HCT-116 and A549 were evaluated under light and darkness,respectively,using the MTT method.9b and 9c show stronger inhibition of proliferation of HCT-116 and A549 cells under light conditions.Finally,molecular docking experiments show that the target compounds have good binding ability to CDK and PI3K.

关 键 词：卟啉 NO供体 卟啉-水杨酸衍生物 光动力治疗 靶向药物 

分 类 号：R9[医药卫生—药学]