Hybrid Analogues of Hydrazone and Phthalimide: Design, Synthesis, In vivo, In vitro, and In silico Evaluation as Analgesic Agents.

IF 1.5 4区医学 Q4 CHEMISTRY, MEDICINAL

Current computer-aided drug design Pub Date : 2024-01-01 DOI:10.2174/1573409919666230517121726

Shahla Shokri, Hoda Ayazi, Mohsen Tamjid, Fatemeh Ghoreishi, Mahsa Shokri, Sogol Badakhshannouri, Nima Naderi, Bahram Daraei, Zahra Mousavi, Asghar Davood

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引用次数: 0

Abstract

Background: Based on the anti-inflammatory and analgesic activity of hydrazone and phthalimide, a new series of hybrid hydrazone and phthalimide pharmacophores was prepared and evaluated as analgesic agents.

Methods: The designed ligands were synthesized by reaction of the appropriate aldehydes and 2- aminophthalimide. Analgesic, cyclooxygenase inhibitory, and cytostatic activity of prepared compounds were measured.

Results: All the tested ligands demonstrated significant analgesic activity. Moreover, compounds 3i and 3h were the most potent ligands in the formalin and writhing tests, respectively. Compounds 3g, 3j, and 3l were the most COX-2 selective ligands and ligand 3e was the most potent COX inhibitor with a 0.79 of COX-2 selectivity ratio. The presence of electron-withdrawing moieties with hydrogen bonding ability at the meta position was found to affect the selectivity efficiently, in which compounds 3g, 3l, and 3k showed high COX-2 selectivity, and compound 3k was the most potent one. The cytostatic activity of selected ligands demonstrated that compounds 3e, 3f, 3h, 3k, and 3m showed good analgesic and COX inhibitory activity and were less toxic than the reference drug.

Conclusion: High therapeutic index of these ligands is one of the valuable advantages of these compounds.

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腙和邻苯二甲酰亚胺的混合类似物：作为镇痛剂的设计、合成、体内、体外和硅学评估。

背景：基于腙和邻苯二甲酰亚胺的抗炎和镇痛活性，制备了一系列新的腙和邻苯二甲酰亚胺杂化配体，并将其作为镇痛剂进行了评估：方法：设计的配体是通过适当的醛和 2- 氨基邻苯二甲酰亚胺反应合成的。对所制备化合物的镇痛、环氧化酶抑制和细胞抑制活性进行了测定：结果：所有受测配体都具有显著的镇痛活性。此外，化合物 3i 和 3h 分别是福尔马林试验和蠕动试验中最有效的配体。化合物 3g、3j 和 3l 是 COX-2 选择性最强的配体，配体 3e 是最有效的 COX 抑制剂，其 COX-2 选择性比为 0.79。研究发现，在元位存在具有氢键能力的夺电子分子会有效地影响选择性，其中化合物 3g、3l 和 3k 显示出较高的 COX-2 选择性，而化合物 3k 是最强的一种。所选配体的细胞抑制活性表明，化合物 3e、3f、3h、3k 和 3m 具有良好的镇痛和 COX 抑制活性，且毒性低于参考药物：结论：这些配体的高治疗指数是这些化合物的宝贵优势之一。

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

Current computer-aided drug design 医学-计算机：跨学科应用

CiteScore

3.70

自引率

5.90%

发文量

审稿时长

>12 weeks

期刊介绍： Aims & Scope Current Computer-Aided Drug Design aims to publish all the latest developments in drug design based on computational techniques. The field of computer-aided drug design has had extensive impact in the area of drug design. Current Computer-Aided Drug Design is an essential journal for all medicinal chemists who wish to be kept informed and up-to-date with all the latest and important developments in computer-aided methodologies and their applications in drug discovery. Each issue contains a series of timely, in-depth reviews, original research articles and letter articles written by leaders in the field, covering a range of computational techniques for drug design, screening, ADME studies, theoretical chemistry; computational chemistry; computer and molecular graphics; molecular modeling; protein engineering; drug design; expert systems; general structure-property relationships; molecular dynamics; chemical database development and usage etc., providing excellent rationales for drug development.