Design, synthesis, molecular dynamics and in silico pharmacokinetic study of N-(4-(thiazol-2-ylamino)phenyl)benzamide analogues as promising anti-inflammatory agents

IF 2.5 4区化学 Q2 Engineering

Chemical Papers Pub Date : 2025-12-08 DOI:10.1007/s11696-025-04535-1

Manoj Kashyap, Muslek Uddin Mazumder, Pooja Patowary, Lalnun Hruaitluangi, Lalzikpuii Sailo, Babita Deka, Debaprotim Dasgupta, Apurba Talukdar, Bhargab Jyoti Sahariah

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Abstract

Six N-(4-(thiazol-2-ylamino)phenyl)benzamide derivatives (MK1–MK6) were designed and synthesized as potential anti-inflammatory agents. Among them, N-(4-(benzo[d]thiazol-2-ylamino)phenyl)benzamide (MK2) exhibited the highest activity in the in vitro protein denaturation inhibition assay (98.99 µg/mL), comparable to diclofenac (91.32 µg/mL). In the in vivo carrageenan-induced rat paw edema model, MK2 produced a significant reduction in paw volume (p < 0.001) at both low and high doses, demonstrating potent anti-inflammatory efficacy. Acute toxicity evaluation confirmed its safety up to 550 mg/kg. In silico molecular docking and 100 ns dynamics simulation against cyclooxygenase-2 (PDB ID: 3PGH) showed strong and stable binding interactions, particularly for MK2. ADME and drug-likeness analysis indicated favorable pharmacokinetic properties, including high gastrointestinal absorption and compliance with Lipinski’s rule of five. Overall, compound MK2 emerged as the most promising lead with excellent biological performance across in vitro, in vivo, and in silico studies, supporting its potential as a safe and effective anti-inflammatory candidate.

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N-（4-（噻唑-2-氨基）苯基）苯酰胺类似物的设计、合成、分子动力学和计算机药代动力学研究

设计并合成了6种N-（4-（噻唑-2-氨基）苯基）苯酰胺衍生物（MK1-MK6）。其中，N-（4-（苯并[d]噻唑-2-氨基）苯基）苯甲酰胺（MK2）在体外蛋白变性抑制实验中表现出最高的活性（98.99µg/mL），与双氯芬酸（91.32µg/mL）相当。在体内卡拉胶诱导的大鼠足部水肿模型中，MK2在低剂量和高剂量下均能显著减少足部体积（p < 0.001），显示出强大的抗炎功效。急性毒性评价证实其安全性可达550 mg/kg。与环氧化酶-2 （PDB ID: 3PGH）的硅分子对接和100 ns动力学模拟显示了强而稳定的结合相互作用，特别是对MK2。ADME和药物相似性分析显示良好的药代动力学特性，包括高胃肠道吸收和符合Lipinski的五项规则。总的来说，化合物MK2在体外、体内和计算机研究中表现优异，是最有希望的先导物，支持其作为一种安全有效的抗炎候选药物的潜力。图形抽象此图像的替代文本可能是使用AI生成的。

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来源期刊

Chemical Papers Chemical Engineering-General Chemical Engineering

CiteScore

3.30

自引率

4.50%

发文量

590

期刊介绍： Chemical Papers is a peer-reviewed, international journal devoted to basic and applied chemical research. It has a broad scope covering the chemical sciences, but favors interdisciplinary research and studies that bring chemistry together with other disciplines.