Synthesis, telomerase inhibitory and anticancer activity of new 2-phenyl-4H-chromone derivatives containing 1, 3, 4-oxadiazole moiety. (1st January 2021)

• Record Type: Journal Article
• Authors: Han, Xu; Yu, Yun Long; Ma, Duo; Zhang, Zhao Yan; Liu, Xin Hua
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 36:Number 1(2021)
• Page Start: 345
• Page End: 361
• Publication Date: 2021-01-01
• Subjects: 2-phenyl-4H-chromone -- synthesis -- telomerase inhibitor -- anticancer activity -- dyskerin; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.1080/14756366.2020.1864630
• Languages: English
• ISSNs: 1475-6366

Abstract

Abstract: Based on previous studies, 66 2-phenyl-4H-chromone derivatives containing amide and 1, 3, 4-oxadiazole moieties were prepared as potential telomerase inhibitors. The results showed most of the title compounds exhibited significantly inhibitory activity on telomerase. Among them, some compounds demonstrated the most potent telomerase inhibitory activity (IC50 < 1 µM), which was significantly superior to the staurosporine (IC50 = 6.41 µM). In addition, clear structure–activity relationships were summarised, indicating that the substitution of the methoxy group and the position, type and number of the substituents on the phenyl ring had significant effects on telomerase activity. Among them, compound A33 showed considerable inhibition against telomerase. Flow cytometric analysis showed that compound A33 could arrest MGC-803 cell cycle at G2/M phase and induce apoptosis in a concentration-dependent way. Meanwhile, Western blotting revealed that this compound could reduce the expression of dyskerin, which is a fragment of telomerase.