噻吩并[3,2-e]吲唑衍生物的合成、抗增殖评价和分子对接

IF 1.2 4区 医学 Q4 CHEMISTRY, MEDICINAL
Rafat M. Mohareb, Ibram Refat Mikhail, Marwa Soliman Gamaan, Ensaf S. Alwan
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引用次数: 0

摘要

背景:尽管吲唑衍生物十分罕见,而且在自然界中可能不易获得,但有许多报告显示了它们在制药和其他方面的应用。研究目的本研究旨在合成新的吲唑衍生物并评估其抗增殖活性,以生产新的抗癌药物。研究方法通过环己烷-1,3-二酮与用于合成噻吩并[3,2-e]吲唑衍生物的芳香醛反应,得到 2-芳基亚甲基环己烷-1,3-二酮衍生物 3a-c。这些衍生物通过大量的分析和光谱研究得到了表征,并被进一步用作某些杂环转化的起始材料,以生产具有生物活性的化合物。研究人员评估了新合成化合物对 A549、HT-29、MKN-45、U87MG、SMMC-7721 和 H460 六种癌细胞株的抗增殖活性。除少数化合物外,大多数受测化合物都表现出较高的细胞毒性。研究结果本研究对新化合物进行了合成、表征,并对所选的六种癌细胞系进行了评估。所有测试化合物都显示出了强效的 c-Met 酶活性,IC50 值在 0.25 至 10.30 nM 之间,对前列腺 PC-3 细胞株的强效抑制作用,IC50 值在 0.17 至 9.31mM 之间。结论这项研究的结果表明,芳基中取代基的变化以及所附杂环对抗增殖活性有显著影响。本研究取得的结果鼓励今后开展更多的工作。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Synthesis, Antiproliferative Evaluation, and Molecular Docking of Thieno[3,2-e]indazole Derivatives
Background: Although indazole derivatives are rare and may not be available easily in nature, there are many reports demonstrating their pharmaceutical and other applications. Objective: This study aimed to synthesize new indazole derivatives and evaluate their antiproliferative activity to produce new anti-cancer agents. Method: The 2-aryllidenecyclohexane-1,3-dione derivatives 3a-c were obtained through the reaction of cyclohexane-1,3-dione with aromatic aldehydes used for the synthesis of thieno-[3,2-e]indazole derivatives. These derivatives were characterized by extensive analytical and spectral studies and were further used as starting materials for some heterocyclic transformations to produce biologically active compounds. The antiproliferative activities of the newly synthesized compounds were evaluated against the six cancer cell lines, A549, HT-29, MKN-45, U87MG, SMMC-7721, and H460. Most of the tested compounds exhibited high cytotoxicity except a few compounds. Results: In this study, new compounds were synthesized, characterized, and evaluated toward the selected six cancer cell lines. All tested compounds displayed potent c-Met enzymatic activity with IC50 values ranging from 0.25 to 10.30 nM and potent prostate PC-3 cell line inhibition with IC50 values ranging from 0.17 to 9.31mM. Conclusion: The results obtained in this work demonstrated that the variations in substituents within the aryl moiety, together with the attached heterocyclic ring, have a notable influence on the antiproliferative activity. The results obtained in this work encourage further work in the future.
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来源期刊
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.
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