Synthesis and Biological Evaluation of 4-substituted Aryl-piperazine Derivatives of 1,7,8,9-tetrachloro-10,10-dimethoxy-4-azatricyclo [5.2.1.02,6] dec-8-ene-3,5-dione as Anti-cancer and Anti-angiogenesis Agents

IF 1.2 4区医学 Q4 CHEMISTRY, MEDICINAL

Letters in Drug Design & Discovery Pub Date : 2023-10-01 DOI:10.2174/1570180819666220816114613

Lifang Guo, Benshan Xu, Bin Hu, He Liu, Nan Song

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引用次数: 0

Abstract

Background: A series of aryl-piperazine derivatives of 1,7,8,9-tetrachloro-10,10-dimethoxy-4- azatricyclo [5.2.1.02,6] dec-8-ene-3,5-dione were designed, synthesized, and their biological activities were evaluated. Methods: The chemical structures of the desired compounds were identified by 1H NMR, ESI-MS and elementary analysis. The anti-cancer and anti-angiogenesis activities of the newly synthesized compounds were evaluated by proliferation and migration assays, respectively. Results: The screening results demonstrated that compounds 2 and 5 showed potent anti-tumor activity (IC50 values ranging from 7.1 to 15.9μM) with low cytotoxic activities (IC50＞79.3μM). Although compound 5 had no effects on endothelial proliferation (IC50=65.3μM), it significantly abrogated endothelial cell migration (IC50=6.7μM). Conclusion: This work may impart new direction for the investigations of aryl-piperazine derivatives and lead to the development of potent novel anti-tumor and anti-angiogenesis agents.

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抗癌和抗血管生成剂1,7,8,9-四氯-10,10-二甲氧基-4-氮杂环[5.2.1.02,6]十二-8-烯-3,5-二酮的4-取代芳基哌嗪衍生物的合成及生物学评价

背景:设计、合成了一系列1,7,8,9-四氯-10,10-二甲氧基-4-扎扎环[5.2.1.02,6]十二-8-烯-3,5-二酮的芳基哌嗪衍生物，并对其生物活性进行了评价。方法:采用1H NMR、ESI-MS、元素分析等方法鉴定化合物的化学结构。新合成的化合物分别通过增殖和迁移实验对其抗癌活性和抗血管生成活性进行了评价。结果:筛选结果表明，化合物2和5具有较强的抗肿瘤活性(IC50值为7.1 ~ 15.9μM)，细胞毒活性较低(IC50值>79.3μM)。化合物5对内皮细胞增殖无影响(IC50=65.3μM)，但明显抑制内皮细胞迁移(IC50=6.7μM)。结论:本研究为芳基哌嗪类衍生物的研究提供了新的方向，并为开发新型有效的抗肿瘤和抗血管生成药物奠定了基础。

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来源期刊

Letters in Drug Design & Discovery 医学-医药化学

CiteScore

1.80

自引率

10.00%

发文量

245

审稿时长

3 months

期刊介绍： Aims & Scope Letters in Drug Design & Discovery publishes letters, mini-reviews, highlights and guest edited thematic issues in all areas of rational drug design and discovery including medicinal chemistry, in-silico drug design, combinatorial chemistry, high-throughput screening, drug targets, and structure-activity relationships. The emphasis is on publishing quality papers very rapidly by taking full advantage of latest Internet technology for both submission and review of manuscripts. The online journal is an essential reading to all pharmaceutical scientists involved in research in drug design and discovery.