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揭示具有选择性黄嘌呤氧化酶抑制作用的强效席夫碱衍生物:一种计算方法。

Unveiling potent Schiff base derivatives with selective xanthine oxidase inhibition: and approach.

作者信息

Bellahcene Fatna, Benarous Khedidja, Mermer Arif, Boulebd Houssem, Serseg Talia, Linani Abderahmane, Kaouka Alaeddine, Yousfi Mohamed, Syed Asad, Elgorban Abdallah M, Ozeki Yasuhiro, Kawsar Sarkar M A

机构信息

Laboratory of Fundamental Sciences, Faculty of Sciences, University of Amar Telidji, Laghouat, Algeria.

Department of Biotechnology, University of Health Sciences, İstanbul, Turkey.

出版信息

Saudi Pharm J. 2024 May;32(5):102062. doi: 10.1016/j.jsps.2024.102062. Epub 2024 Apr 4.

Abstract

This research describes the synthesis by an environmentally-friendly method, microwave irradiation, development and analysis of three novel and one previously identified Schiff base derivative as a potential inhibitor of bovine xanthine oxidase (BXO), a key enzyme implicated in the progression of gout. Meticulous experimentation revealed that these compounds (, , , and ) have noteworthy inhibitory effects on BXO, with IC50 values ranging from 149.56 µM to 263.60 µM, indicating their good efficacy compared to that of the standard control. The validation of these results was further enhanced through comprehensive in silico studies, which revealed the pivotal interactions between the inhibitors and the catalytic sites of BXO, with a particular emphasis on the imine group (-C = N-) functionalities. Intriguingly, the compounds exhibiting the highest inhibition rates also showcase advantageous ADMET profiles, alongside encouraging initial assessments via PASS, hinting at their broad-spectrum potential. The implications of these findings are profound, suggesting that these Schiff base derivatives not only offer a new vantage point for the inhibition of BXO but also hold considerable promise as innovative therapeutic agents in the management and treatment of gout, marking a significant leap forward in the quest for more effective gout interventions.

摘要

本研究描述了通过微波辐射这种环保方法合成、开发并分析三种新型席夫碱衍生物以及一种先前已鉴定的席夫碱衍生物,它们作为牛黄嘌呤氧化酶(BXO)的潜在抑制剂,而牛黄嘌呤氧化酶是痛风进展中涉及的一种关键酶。细致的实验表明,这些化合物(、、和)对BXO具有显著的抑制作用,IC50值在149.56 µM至263.60 µM之间,表明与标准对照相比它们具有良好的功效。通过全面的计算机模拟研究进一步加强了这些结果的验证,该研究揭示了抑制剂与BXO催化位点之间的关键相互作用,特别强调了亚胺基团(-C = N-)的功能。有趣的是,表现出最高抑制率的化合物还展现出有利的药物代谢动力学、药物代谢和毒性概况,同时通过PASS进行的初步评估令人鼓舞,暗示了它们的广谱潜力。这些发现的意义深远,表明这些席夫碱衍生物不仅为抑制BXO提供了一个新的视角,而且在痛风的管理和治疗中作为创新治疗剂也具有相当大的前景,标志着在寻求更有效的痛风干预措施方面向前迈出了重要一步。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81ec/11004395/68e6e9334130/ga1.jpg

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