通过 1,4-二极环加成反应合成新型苯并噻吩-[3,2'-f][1,3] 氧氮杂卓及其异构体 2-氧代-2H-螺[苯并噻吩-3,3'-吡咯啉]，并将其作为细胞毒性抗癌药物进行评估

IF 2.6 4区医学 Q3 CHEMISTRY, MEDICINAL

Medicinal Chemistry Research Pub Date : 2024-05-11 DOI:10.1007/s00044-024-03229-9

Mohammed M. Al-Mahadeen, Areej M. Jaber, Jalal A. Zahra, Mustafa M. El-Abadelah, Walhan Alshaer, Mutasem O. Taha

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引用次数: 0

摘要

本研究介绍了一类新型杂化化合物，即苯并噻吩并[3,2'-f][1,3]氧氮杂卓及其异构体 2-氧代-2H-螺[苯并噻吩-3,3'-吡咯烷]。合成策略采用了三组分反应和 1,4-二极环化反应，生成了螺环和氧氮杂卓化合物。通过核磁共振和质谱分析进行结构阐释，并辅以 X 射线晶体学和拟议的机理途径。针对 HEK-293 和 HT-29 细胞的生物学评估显示，化合物对 HEK-293 具有强效的选择性细胞毒性，但对 HT-29 细胞无细胞毒性作用。化合物 16c 对 HEK-293 细胞的细胞毒性最高，IC50 = 4.30 μM。因此，这些新化合物可被视为有希望优化为新型选择性细胞毒性疗法的线索。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Synthesis of novel benzothieno-[3,2’-f][1,3] oxazepines and their isomeric 2-oxo-2H-spiro[benzothiophene-3,3’-pyrrolines] via 1,4-dipolar cycloaddition reaction and their evaluation as cytotoxic anticancer leads

查看原文本刊更多论文

This study introduces a novel class of hybrid compounds, namely, benzothieno[3,2’-f][1,3]oxazepines and their isomeric 2-oxo-2H-spiro[benzothiophene-3,3’-pyrrolines]. The synthetic strategy employs a three-component reaction and 1,4-Dipolar cycloaddition, yielding spiro and oxazepine compounds. Structural elucidation via NMR and MS analyses is complemented by X-ray crystallography and a proposed mechanistic pathway. Biological evaluation against HEK-293 and HT-29 cells reveals potent and selective cytotoxicity against HEK-293 without cytotoxic effects against HT-29 cells. Compound 16c exhibited the highest cytotoxic properties with IC₅₀ = 4.30 μM against HEK-293 cells. Accordingly, the new compounds can be considered as promising leads for possible optimization into novel selective cytotoxic treatments.

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来源期刊

Medicinal Chemistry Research 医学-医药化学

CiteScore

4.70

自引率

3.80%

发文量

162

审稿时长

5.0 months

期刊介绍： Medicinal Chemistry Research (MCRE) publishes papers on a wide range of topics, favoring research with significant, new, and up-to-date information. Although the journal has a demanding peer review process, MCRE still boasts rapid publication, due in part, to the length of the submissions. The journal publishes significant research on various topics, many of which emphasize the structure-activity relationships of molecular biology.