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

{"title":"Design, synthesis, In Silico analysis, anti-inflammatory, and cytotoxicity evaluation of Novel Formyl-Pyrazoline derivatives","authors":"Yogeesha N Nayak , Samyak Pandey , Sreedhara Ranganath Pai , Neha S Gandhi , Raksha Nayak , Zhang Xi , Vijay Pandey , Basappa Basappa , Santosh L. Gaonkar","doi":"10.1016/j.molstruc.2024.140821","DOIUrl":null,"url":null,"abstract":"<div><div>A novel series of formyl-pyrazoline derivatives was synthesised through a well-defined pathway utilising chalcones as key intermediates. These derivatives were characterised using <sup>1</sup>H NMR, <sup>13</sup>C 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 <strong>(5f)</strong> 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 <strong>(5d)</strong> displayed a significant IC₅₀ value of 14.181 µM. Molecular docking was employed to explore the binding interactions of the protein-ligand complex (PDB: <span><span>4COX</span><svg><path></path></svg></span>), 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.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1324 ","pages":"Article 140821"},"PeriodicalIF":4.0000,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Molecular Structure","FirstCategoryId":"92","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0022286024033295","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, PHYSICAL","Score":null,"Total":0}

引用次数: 0

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.

Abstract Image

查看原文本刊更多论文

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。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

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.