文献类型：期刊文献

英文题名：Discovery of novel 2-aminonicotinonitrile derivatives with new potential autophagy activity

作者：Zhang, Pinghu[1,2,3] Zheng, Zuguo[3] Yang, Xiaohui[4] Zhang, Yuqian[1,2] Hu, Gendi[3] Wang, Ronghua[1,2] Dong, Yu[5] Wei, Dongping[6]

第一作者：Zhang, Pinghu

通信作者：Zhang, PH[1];Zhang, PH[2];Zhang, PH[3]

机构：[1]Yangzhou Univ, Inst Translat Med, Yangzhou 225009, Jiangsu, Peoples R China;[2]Yangzhou Univ, Jiangsu Key Lab Integrated Tradit Chinese & Weste, Coll Med, Yangzhou 225009, Jiangsu, Peoples R China;[3]China Pharmaceut Univ, Jiangsu Key Lab New Drug Screening, Nanjing 211198, Peoples R China;[4]Chinese Acad Forestry, Inst Chem Ind Forest Prod, Key Lab Biomass Energy & Mat, Nanjing 210042, Jiangsu, Peoples R China;[5]Zhejiang Acad Tradit Chinese Med, Dept Med, Hangzhou 310007, Peoples R China;[6]Nanjing Med Univ, Dept Oncol, Nanjing Hosp 1, Nanjing 210042, Peoples R China

年份：2020

卷号：12

期号：15

起止页码：1399-1414

外文期刊名：FUTURE MEDICINAL CHEMISTRY

收录：;Scopus(收录号：2-s2.0-85090075305);WOS:【SCI-EXPANDED(收录号:WOS:000598232300005)】；

基金：This study was supported in part by the Program for New Century Excellent Talents in University (program no. NCET-12-0975 for Pinghu Zhang); the National Natural Science Foundation of China (grant no. 31890773 for Xiaohui Yang; 81472793 and 81672895 for Dongping Wei) and the Research Funds of Jiangsu Key Laboratory for Biomass Energy and Material (grant no. JSBEM-S-201803 for Xiaohui Yang). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

语种：英文

外文关键词：2-aminonicotinonitrile; anticancer activity; apoptosis; autophagy

摘要：Background: To clarify the molecular mechanism of novel 2-aminonicotinonitrile autophagy enhancers, two series of novel 2-aminonicotinonitrile derivatives are synthesized and their structure-activity relationship and biological activity were analyzed. Results & methodology: Structure-activity relationship analysis revealed that substituents at C-4 and C-6 position of 7a contribute to enhance their autophagy-inducing activity, while C-5 position substituents have the opposite effect. The most promising compound 7g showed the strongest autophagy-inducing activity and better antiproliferative activity by inducing cell apoptosis and blocking cell cycle G1 arrest in SGC-7901 cells. Conclusion: The novel 2-aminonicotinonitrile autophagy enhancers were for the first time discovered and 7g might be a promising new autophagy enhancer with potential anticancer activity.