Sustainable one-pot synthesis, digital ADMET modelling, DFT analysis, molecular docking and biological screening of dibutyl((5-hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)(aryl)methyl) phosphonates

IF 2.8 3区化学 Q2 CHEMISTRY, MULTIDISCIPLINARY

Research on Chemical Intermediates Pub Date : 2025-04-24 DOI:10.1007/s11164-025-05590-9

Sumithra Poreddy, Mohan Gundluru, Surendra Pothuraju, Poojitha Bellala, Jyothibabu Sajila Arya, Suresh Reddy Cirandur

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引用次数: 0

Abstract

This study presents a sustainable one-pot synthesis of novel pyrazolyl phosphonate derivatives via a three-component reaction using 3-methyl-1-phenyl-2-pyrazoline-5-one, aryl aldehydes and dibutyl phosphite, catalyzed by thiamine hydrochloride under solvent-free conditions. Two of these synthetic chemicals were chosen for in-depth density functional theory analysis due to their electron-donating (methoxy) and electron-withdrawing (nitro) groups, providing insights into their electronic properties, reactivity and stability through highest occupied molecular orbital-lowest unoccupied molecular orbital energy gap calculations. Strong interactions with the active sites of acetylcholinesterase (AChE) were found by molecular docking experiments. The compounds also exhibited potent anti-inflammatory and antioxidant activities in biological assays. Additionally, absorption, distribution, metabolism, excretion and toxicity profiling suggested favourable bioavailability and low toxicity, demonstrating their medicinal potential in the creation of new drugs.

Graphical abstract

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可持续一锅合成，数字ADMET建模，DFT分析，分子对接和（5-羟基-3-甲基-1-苯基- 1h -吡唑-4-基）（芳基）甲基)膦酸酯的生物筛选

在无溶剂条件下，以盐酸硫胺素为催化剂，以3-甲基-1-苯基-2-吡唑啉-5-酮、芳醛和亚磷酸二丁酯为原料，采用一锅法合成了新型吡唑酰膦酸酯衍生物。选择其中两种合成化学物质进行深入的密度功能理论分析，因为它们具有给电子（甲氧基）和吸电子（硝基）基团，通过计算最高占据的分子轨道和最低未占据的分子轨道能隙，可以深入了解它们的电子性质、反应性和稳定性。通过分子对接实验，发现其与乙酰胆碱酯酶（AChE）活性位点存在强相互作用。这些化合物在生物实验中也显示出强大的抗炎和抗氧化活性。此外，吸收、分布、代谢、排泄和毒性分析表明其具有良好的生物利用度和低毒性，表明其在新药开发中的药用潜力。图形抽象

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来源期刊

Research on Chemical Intermediates 化学-化学综合

CiteScore

5.70

自引率

18.20%

发文量

229

审稿时长

2.6 months

期刊介绍： Research on Chemical Intermediates publishes current research articles and concise dynamic reviews on the properties, structures and reactivities of intermediate species in all the various domains of chemistry. The journal also contains articles in related disciplines such as spectroscopy, molecular biology and biochemistry, atmospheric and environmental sciences, catalysis, photochemistry and photophysics. In addition, special issues dedicated to specific topics in the field are regularly published.