Design and synthesis of indole-based elipticine analogues as topoisomerase IIβ inhibitors

IF 2.6 4区医学 Q3 CHEMISTRY, MEDICINAL

Medicinal Chemistry Research Pub Date : 2024-05-28 DOI:10.1007/s00044-024-03222-2

Mardia T. El Sayed, Alaadin E. Sarhan, Huriyyah A. Alturaifi, Selwan M. El-Sayed, Ghada S. Hassan, Nehal A. Hamdy, Shahenda M. El-Messery, Mamdouh M. Ali

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Abstract

New ellipticine analogs with indole cores were synthesized. and evaluated for their anticancer activity. A new compound, scaffolds, revealed broad-spectrum anticancer potential in one-dose and five doses screening. against the full 60-cell line at NCI. Compounds 2a and 3c had been selected for five-dose screening, where they showed marked anticancer activity against the tested cell lines with an average GI₅₀ (MG-MID) value of 2.23 and 0.98 mM, respectively. Compounds 2a, 2b, 2d, 3b, 3c, and 12 showed noted Topoisomerase Type IIβ inhibitory activity with inhibition records 85.45, 94.7, 93.5, 91.6, 89, and 94.5 percent, respectively. Molecular modeling studies and physicochemical parameter calculations of the most active compounds confirmed their safe. drug-like properties. as a promising anticancer class.

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作为拓扑异构酶 IIβ 抑制剂的吲哚基环丁烷类似物的设计与合成

合成了以吲哚为核心的新型鞣花啶类似物，并对其抗癌活性进行了评估。一种新化合物 "支架 "在一剂和五剂筛选中显示出广谱抗癌潜力。化合物 2a 和 3c 被选中进行五剂量筛选，它们对受试细胞系显示出明显的抗癌活性，平均 GI50（MG-MID）值分别为 2.23 和 0.98 mM。化合物 2a、2b、2d、3b、3c 和 12 具有显著的拓扑异构酶 IIβ 抑制活性，抑制率分别为 85.45%、94.7%、93.5%、91.6%、89% 和 94.5%。对最具活性的化合物进行的分子建模研究和理化参数计算证实，这些化合物具有安全的类药物特性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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.