Skeletal modifications of \(\upbeta \) -carboline alkaloids and their antiviral activity profile

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• 作者：Yan Yang ; Yuanqiong Huang ; Hongjian Song ; Yuxiu Liu ; Lizhong Wang…
• 关键词：\(\upbeta \) ; Carboline alkaloids ; Tobacco mosaic virus ; X ; ray structure ; Anti ; TMV ; Structure ; activity relationship
• 刊名：Molecular Diversity
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：20
• 期：4
• 页码：829-835
• 全文大小：896 KB
• 刊物类别：Chemistry and Materials Science
• 刊物主题：Chemistry
  Analytical Chemistry
  Polymer Sciences
  Organic Chemistry
  Pharmacy
  
• 出版者：Springer Netherlands
• ISSN：1573-501X
• 卷排序：20

文摘

To study the effect of the variation of fused ring size and substitution on the antiviral activity of \(\upbeta \)-carboline alkaloids, four types of structurally novel \(\upbeta \)-carboline alkaloids analogues, with indole-fused six- to nine-membered-rings motifs, were designed, synthesized, and evaluated for the inhibition of tobacco mosaic virus (TMV). Bioassay results indicated that most of these analogues had significant anti-TMV activity; especially I-14 (54 \(\pm \) 3 % at 500 \(\upmu \)g/mL in vitro; 51 \(\pm \) 2, 45 \(\pm \) 2, and 42 \(\pm \) 1 % at 500 \(\upmu \)g/mL in vivo), II-4 (53 \(\pm \) 1 % at 500 \(\upmu \)g/mL in vitro; 49 \(\pm \) 2, 57 \(\pm \) 2, and 48 \(\pm \) 1 % at 500 \(\upmu \)g/mL in vivo), and II-8 (48 \(\pm \) 1 % at 500 \(\upmu \)g/mL in vitro; 53 \(\pm \) 2 %, 56 \(\pm \) 2 %, and 46 \(\pm \) 1 % at 500 \(\upmu \)g/mL in vivo), which were more potent vs. TMV than was ribavirin (36 \(\pm \) 1 % at 500 \(\upmu \)g/mL in vitro; 37 \(\pm \) 2, 41 \(\pm \) 2, and 38 \(\pm \) 1 % at 500 \(\upmu \)g/mL in vivo). The size of the fused ring has important effects on anti-TMV potency, which may be ascribed to conformational differences. The X-ray structures of I-1, I-6, II-8, and III show differing conformational preferences. The most potent compounds can be used as leads for further optimization as antiphytoviral agents.