Design, synthesis, In Silico analysis, anti-inflammatory, and cytotoxicity evaluation of Novel Formyl-Pyrazoline derivatives

IF 4 2区化学 Q2 CHEMISTRY, PHYSICAL Journal of Molecular Structure Pub Date : 2024-11-21 DOI:10.1016/j.molstruc.2024.140821

Yogeesha N Nayak , Samyak Pandey , Sreedhara Ranganath Pai , Neha S Gandhi , Raksha Nayak , Zhang Xi , Vijay Pandey , Basappa Basappa , Santosh L. Gaonkar

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Abstract

A novel series of formyl-pyrazoline derivatives was synthesised through a well-defined pathway utilising chalcones as key intermediates. These derivatives were characterised using ¹H NMR, ¹³C NMR, FTIR and mass spectrometry. The anti-inflammatory activity was evaluated using the carrageenan-induced paw edema model, revealing a spectrum of anti-inflammatory effects ranging from 30.73 % to 52.29 %. Notably, the ortho-nitrile substituted pyrazoline (5f) exhibited superior anti-inflammatory activity, with a percentage inhibition of 52.29 %, compared to other compounds in the series. Furthermore, the cytotoxic effects on the viability of MCF-7 breast cancer cells were evaluated. Here, the meta-chloro substituted pyrazoline (5d) displayed a significant IC₅₀ value of 14.181 µM. Molecular docking was employed to explore the binding interactions of the protein-ligand complex (PDB: 4COX), and molecular dynamics simulations confirmed the stability of the complex. Additionally, the ADME properties of the derivatives were studied to predict the pharmacokinetics of the synthesised pyrazolines.

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新型甲酰基吡唑啉衍生物的设计、合成、In Silico 分析、抗炎和细胞毒性评估

利用查耳酮作为关键中间体，通过明确的途径合成了一系列新型甲酰基吡唑啉衍生物。使用 1H NMR、13C NMR、傅立叶变换红外光谱和质谱法对这些衍生物进行了表征。使用卡拉胶诱导的爪水肿模型对其抗炎活性进行了评估，结果表明其抗炎效果范围为 30.73% 至 52.29%。值得注意的是，与该系列中的其他化合物相比，被原腈取代的吡唑啉（5f）表现出更强的抗炎活性，抑制百分比为 52.29%。此外，还评估了其对 MCF-7 乳腺癌细胞活力的细胞毒性作用。其中，元氯取代的吡唑啉（5d）显示出显著的 IC₅₀ 值，即 14.181 µM。研究人员采用分子对接法探索了蛋白质-配体复合物（PDB：4COX）的结合相互作用，分子动力学模拟证实了该复合物的稳定性。此外，还研究了衍生物的 ADME 特性，以预测合成吡唑啉类化合物的药代动力学。

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来源期刊

Journal of Molecular Structure 化学-物理化学

CiteScore

7.10

自引率

15.80%

发文量

2384

审稿时长

45 days

期刊介绍： The Journal of Molecular Structure is dedicated to the publication of full-length articles and review papers, providing important new structural information on all types of chemical species including: • Stable and unstable molecules in all types of environments (vapour, molecular beam, liquid, solution, liquid crystal, solid state, matrix-isolated, surface-absorbed etc.) • Chemical intermediates • Molecules in excited states • Biological molecules • Polymers. The methods used may include any combination of spectroscopic and non-spectroscopic techniques, for example: • Infrared spectroscopy (mid, far, near) • Raman spectroscopy and non-linear Raman methods (CARS, etc.) • Electronic absorption spectroscopy • Optical rotatory dispersion and circular dichroism • Fluorescence and phosphorescence techniques • Electron spectroscopies (PES, XPS), EXAFS, etc. • Microwave spectroscopy • Electron diffraction • NMR and ESR spectroscopies • Mössbauer spectroscopy • X-ray crystallography • Charge Density Analyses • Computational Studies (supplementing experimental methods) We encourage publications combining theoretical and experimental approaches. The structural insights gained by the studies should be correlated with the properties, activity and/ or reactivity of the molecule under investigation and the relevance of this molecule and its implications should be discussed.