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Discovery of novel 2-aminonicotinonitrile derivatives with new potential autophagy activity.

Authors
  • Zhang, Pinghu1, 2
  • Zheng, Zuguo2
  • Yang, Xiaohui3
  • Zhang, Yuqian1
  • Hu, Gendi2
  • Wang, Ronghua1
  • Dong, Yu4
  • Wei, Dongping5
  • 1 Institute of Translational Medicine & Jiangsu Key Laboratory of Integrated Traditional Chinese & Western Medicine for Prevention & Treatment of Senile Diseases, Medical College, Yangzhou University, Yangzhou, 225009, China. , (China)
  • 2 Jiangsu Key Laboratory for New Drug Screening, China Pharmaceutical University, Nanjing, 211198, China. , (China)
  • 3 Key Laboratory of Biomass Energy & Material, Jiangsu Province, Institute of Chemical Industry of Forest Products, Chinese Academy of Forestry, Nanjing, 210042, China. , (China)
  • 4 Department of Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, 310007, China. , (China)
  • 5 Department of Oncology, Nanjing First Hospital Nanjing Medical University, Nanjing, 210042, China. , (China)
Type
Published Article
Journal
Future Medicinal Chemistry
Publisher
"Future Science, LTD"
Publication Date
Aug 01, 2020
Volume
12
Issue
15
Pages
1399–1414
Identifiers
DOI: 10.4155/fmc-2019-0244
PMID: 32705902
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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.

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