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.
Jiangsu Key Laboratory for New Drug Screening, China Pharmaceutical University, Nanjing, 211198, China.
Future Med Chem. 2020 Aug;12(15):1399-1414. doi: 10.4155/fmc-2019-0244. Epub 2020 Jul 24.
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. Structure-activity relationship analysis revealed that substituents at C-4 and C-6 position of contribute to enhance their autophagy-inducing activity, while C-5 position substituents have the opposite effect. The most promising compound showed the strongest autophagy-inducing activity and better antiproliferative activity by inducing cell apoptosis and blocking cell cycle G1 arrest in SGC-7901 cells. The novel 2-aminonicotinonitrile autophagy enhancers were for the first time discovered and might be a promising new autophagy enhancer with potential anticancer activity.
为了阐明新型 2-氨基烟腈自噬增强剂的分子机制，我们合成了两类新型 2-氨基烟腈衍生物，并对其结构-活性关系和生物活性进行了分析。结构-活性关系分析表明，C-4 和 C-6 位取代基有助于增强其自噬诱导活性，而 C-5 位取代基则有相反的效果。最有前途的化合物 表现出最强的自噬诱导活性和更好的抗增殖活性，通过诱导细胞凋亡和阻断 SGC-7901 细胞的细胞周期 G1 期阻滞。新型 2-氨基烟腈自噬增强剂为首次发现，可能是一种具有潜在抗癌活性的有前途的新型自噬增强剂。
