| 李宇轩,张扬,刘璐,等.海洋生物碱Meridianin G硼酸衍生物的设计、合成及抗单纯疱疹病毒活性研究[1][J].中国海洋药物,2025,(5):-. |
| 海洋生物碱Meridianin G硼酸衍生物的设计、合成及抗单纯疱疹病毒活性研究[1] |
| Design, synthesis and anti-herpes simplex virus evaluation of marine alkaloid Meridianin G boronic acid derivatives |
| 投稿时间：2024-04-22 修订日期：2024-08-21 |
| DOI： |
| 中文关键词: 海洋生物碱 Meridianin G 硼酸 衍生物 抗单纯疱疹病毒活性 |
| English Keywords:Marine alkaloids Meridianin G boronic acid derivatives anti-herpes simplex virus activity |
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| 中文摘要: |
| 目的 本论文对吲哚类海洋生物碱Meridianin G进行硼酸化修饰，设计、合成Meridianin G生物碱硼酸化衍生物，并对其进行体外初步的抗单纯疱疹病毒活性进行研究。方法 采用Meridianin G为起始原料，首先亲核取代反应制备得中间体7a~7c，随后水合肼脱除邻苯二甲酰基得到中间体8a~8c，最后与羧基苯硼酸在缩合剂DMT-MM的催化下合成脂肪胺为连接臂的Meridianin G生物碱硼酸衍生物9a~9f；以5-氨基Meridianin G或6-氨基Meridianin G为起始原料，与羧基苯硼酸进行酰化反应制备得到酰胺键连接的Meridianin G生物碱硼酸衍生物10a~10d。选用Vero细胞株对目标化合物进行了抗单纯疱疹病毒活性的初步测试。结果 合成了10个Meridianin G生物碱硼酸化衍生物，生物活性研究表明该类化合物具有一定的抗单纯疱疹病毒活性，其中脂肪胺为连接臂的Meridianin G生物碱硼酸衍生物9b对单纯疱疹病毒2型有较高的选择性（20 μmol/L浓度下病毒抑制率，2型为50.99%，1型为0.23%）。结论 合成的化合物丰富了吲哚海洋生物碱Meridianin G类似物的种类，抗单纯疱疹病毒生物活性的研究结果扩展了Meridianins类化合物潜在的应用方向并丰富了海洋生物碱的生物功能。 |
| English Summary: |
| Objective In this paper, we designed and synthesized a series of indole marine alkaloid Meridianin G boronic acid derivatives, and their preliminary anti-herpes simplex virus activity in vitro was studied. Methods Using Meridianin G as the starting material, intermediates 7a?7c were prepared via nucleophilic substitution under alkaline conditions, then the phthaloyl group of intermediates 7a?7c was removed by reacting with hydrazine hydrate to obtain intermediate 8a?8c. Finally, aliphatic amine-linked Meridianin G boronic acid derivatives 9a?9f were synthesized by condensing with carboxyphenylboronic acid under the catalysis of DMT-MM. The amide-linked Meridianin G boronic acid derivatives 10a?10d were synthesized by acylation of 5-amino Meridianin G or 6-amino Meridianin G with carboxyphenylboronic acid. Vero cell line was used to preliminarily test the anti-herpes simplex virus activity of the target compounds. Results We synthesized 10 Meridianin G boronic acid derivatives, and their anti-herpes simplex virus activity studies showed that these compounds exhibit different degree of antiviral activity. Among these compounds, the aliphatic amine-linked Meridianin G boronic acid derivative 9b demonstrated higher selectivity against type 2 herpes simplex virus ( at concentration of 20 μmol/L, inhibition rate against type 2 was 50.99%, while against type 1 was 0.23% ). Conclusion The Meridianin G boronic acid derivatives synthesized in this report enrich the diversity of indole marine alkaloids Meridianin G analogues, and their anti-herpes simplex virus activity expand the potential application directions of Meridianins and enrich the biological functions of marine alkaloids. |
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