Nilesh Bhusari, Abhay Bagul, Vipin Kumar Mishra, Aisha Tufail, Digambar Gaikwad and Amit Dubey
{"title":"通过离子液体和微波辅助方法可持续合成希夫碱衍生物:结构,生物和计算评价†","authors":"Nilesh Bhusari, Abhay Bagul, Vipin Kumar Mishra, Aisha Tufail, Digambar Gaikwad and Amit Dubey","doi":"10.1039/D5RA02622A","DOIUrl":null,"url":null,"abstract":"<p >A sustainable and efficient microwave-assisted strategy was developed for the synthesis of novel 4-amino-pyrrolo [2,3-<em>d</em>]pyrimidine-based Schiff base derivatives (<strong>APR1a–d</strong>), utilizing the ionic liquid 1-hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (<strong>[HMIM][TFSI]</strong>) as both catalyst and solvent. This green protocol afforded high yields (82–94%) under mild conditions with excellent reusability of the ionic liquid. Structural confirmation was achieved <em>via</em> FT-IR, <small><sup>1</sup></small>H and <small><sup>13</sup></small>C NMR, and mass spectrometry. The antimicrobial potential of the synthesized compounds was assessed against a panel of Gram-positive and Gram-negative bacteria, as well as pathogenic yeast strains. Among them, <strong>APR1d</strong> exhibited the most potent antibacterial activity (up to 28 mm inhibition against <em>B. subtilis</em>) and broad-spectrum antifungal efficacy (up to 19 mm inhibition against <em>C. albicans</em> and <em>S. cerevisiae</em>). Cytotoxicity analysis <em>via</em> brine shrimp lethality assay indicated low toxicity, with LC<small><sub>50</sub></small> values of 3.50 × 10<small><sup>−4</sup></small> M (<strong>APR1b</strong>) and 8.50 × 10<small><sup>−4</sup></small> M (<strong>APR1c</strong>). Density Functional Theory (DFT) analysis revealed that <strong>APR1d</strong> possessed the smallest HOMO–LUMO gap (0.0679 eV) and highest electrophilicity index (0.4288 eV), supporting its high reactivity. Molecular electrostatic potential maps and global reactivity descriptors (<em>μ</em>, <em>η</em>, <em>S</em>, <em>ω</em>, <em>χ</em>) further elucidated the electronic distribution and interaction potential. Molecular docking and MM/PBSA analyses confirmed <strong>APR1d</strong>'s strong and stable binding to key microbial target proteins, surpassing standard drugs in binding affinity. These results underscore <strong>APR1d</strong> as a promising lead candidate with significant therapeutic potential, while highlighting the synergy of green chemistry, computational modeling, and biological validation in modern drug discovery.</p>","PeriodicalId":102,"journal":{"name":"RSC Advances","volume":" 28","pages":" 22764-22788"},"PeriodicalIF":3.9000,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/ra/d5ra02622a?page=search","citationCount":"0","resultStr":"{\"title\":\"Sustainable synthesis of Schiff base derivatives via an ionic liquid and a microwave-assisted approach: structural, biological, and computational evaluation†\",\"authors\":\"Nilesh Bhusari, Abhay Bagul, Vipin Kumar Mishra, Aisha Tufail, Digambar Gaikwad and Amit Dubey\",\"doi\":\"10.1039/D5RA02622A\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >A sustainable and efficient microwave-assisted strategy was developed for the synthesis of novel 4-amino-pyrrolo [2,3-<em>d</em>]pyrimidine-based Schiff base derivatives (<strong>APR1a–d</strong>), utilizing the ionic liquid 1-hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (<strong>[HMIM][TFSI]</strong>) as both catalyst and solvent. This green protocol afforded high yields (82–94%) under mild conditions with excellent reusability of the ionic liquid. Structural confirmation was achieved <em>via</em> FT-IR, <small><sup>1</sup></small>H and <small><sup>13</sup></small>C NMR, and mass spectrometry. The antimicrobial potential of the synthesized compounds was assessed against a panel of Gram-positive and Gram-negative bacteria, as well as pathogenic yeast strains. Among them, <strong>APR1d</strong> exhibited the most potent antibacterial activity (up to 28 mm inhibition against <em>B. subtilis</em>) and broad-spectrum antifungal efficacy (up to 19 mm inhibition against <em>C. albicans</em> and <em>S. cerevisiae</em>). Cytotoxicity analysis <em>via</em> brine shrimp lethality assay indicated low toxicity, with LC<small><sub>50</sub></small> values of 3.50 × 10<small><sup>−4</sup></small> M (<strong>APR1b</strong>) and 8.50 × 10<small><sup>−4</sup></small> M (<strong>APR1c</strong>). 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引用次数: 0
摘要
以离子液体1-己基-3-甲基咪唑双(三氟甲基磺酰基)亚胺([HMIM][TFSI])为催化剂和溶剂,建立了一种可持续、高效的微波辅助合成新型4-氨基吡咯[2,3-d]嘧啶基希夫碱衍生物(APR1a-d)的方法。该绿色方案在温和的条件下具有较高的收率(82-94%),离子液体具有良好的可重复使用性。通过FT-IR, 1H和13C NMR以及质谱法进行结构确认。对合成化合物的抗菌潜力进行了对一组革兰氏阳性和革兰氏阴性细菌以及致病性酵母菌株的评估。其中,APR1d抗菌活性最强(对枯草芽孢杆菌抑制达28 mm),抗菌效果广谱(对白色念珠菌和酿酒葡萄球菌抑制达19 mm)。盐水对虾致死性细胞毒性分析显示,LC50值为3.50 × 10−4 M (APR1b)和8.50 × 10−4 M (APR1c),毒性较低。密度泛函理论(DFT)分析表明,APR1d具有最小的HOMO-LUMO间隙(0.0679 eV)和最高的亲电性指数(0.4288 eV),具有较高的反应活性。分子静电势图和整体反应性描述符(μ, η, S, ω, χ)进一步阐明了电子分布和相互作用势。分子对接和MM/PBSA分析证实了APR1d与关键微生物靶蛋白的强而稳定的结合,其结合亲和力超过标准药物。这些结果强调了APR1d作为具有显著治疗潜力的有前途的主要候选药物,同时强调了绿色化学,计算建模和现代药物发现中的生物学验证的协同作用。
Sustainable synthesis of Schiff base derivatives via an ionic liquid and a microwave-assisted approach: structural, biological, and computational evaluation†
A sustainable and efficient microwave-assisted strategy was developed for the synthesis of novel 4-amino-pyrrolo [2,3-d]pyrimidine-based Schiff base derivatives (APR1a–d), utilizing the ionic liquid 1-hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([HMIM][TFSI]) as both catalyst and solvent. This green protocol afforded high yields (82–94%) under mild conditions with excellent reusability of the ionic liquid. Structural confirmation was achieved via FT-IR, 1H and 13C NMR, and mass spectrometry. The antimicrobial potential of the synthesized compounds was assessed against a panel of Gram-positive and Gram-negative bacteria, as well as pathogenic yeast strains. Among them, APR1d exhibited the most potent antibacterial activity (up to 28 mm inhibition against B. subtilis) and broad-spectrum antifungal efficacy (up to 19 mm inhibition against C. albicans and S. cerevisiae). Cytotoxicity analysis via brine shrimp lethality assay indicated low toxicity, with LC50 values of 3.50 × 10−4 M (APR1b) and 8.50 × 10−4 M (APR1c). Density Functional Theory (DFT) analysis revealed that APR1d possessed the smallest HOMO–LUMO gap (0.0679 eV) and highest electrophilicity index (0.4288 eV), supporting its high reactivity. Molecular electrostatic potential maps and global reactivity descriptors (μ, η, S, ω, χ) further elucidated the electronic distribution and interaction potential. Molecular docking and MM/PBSA analyses confirmed APR1d's strong and stable binding to key microbial target proteins, surpassing standard drugs in binding affinity. These results underscore APR1d as a promising lead candidate with significant therapeutic potential, while highlighting the synergy of green chemistry, computational modeling, and biological validation in modern drug discovery.
期刊介绍:
An international, peer-reviewed journal covering all of the chemical sciences, including multidisciplinary and emerging areas. RSC Advances is a gold open access journal allowing researchers free access to research articles, and offering an affordable open access publishing option for authors around the world.