T. R. A. Sangma, L. B. Marpna, M. Rymbai, S. Kaping, V. V. Borah, J. N. Vishwakarma
{"title":"Environmentally Friendly Synthesis of Coumarin–Pyrazolo[1,5-a]pyrimidine Hybrids with Potent Antibacterial and Antibiofilm Activities","authors":"T. R. A. Sangma, L. B. Marpna, M. Rymbai, S. Kaping, V. V. Borah, J. N. Vishwakarma","doi":"10.1134/S1068162024606360","DOIUrl":null,"url":null,"abstract":"<p><b>Objective:</b> This study aimed to synthesize a series of coumarin–pyrazolo[1,5-<i>a</i>]pyrimidine hybrid compounds and evaluate their potential antibacterial and antibiofilm activities. <b>Methods:</b> In our synthetic approach, a mixture of 3-acetylcoumarin (<b>I</b>) and <i>N</i>,<i>N</i>-dimethylformamide dimethyl acetal (DMF-DMA) was refluxed in toluene to afford the enaminone intermediate (<b>II</b>). Subsequent condensation with 3-aminopyrazoles in the presence of potassium hydrogen sulfate (KHSO<sub>4</sub>) yielded a series of 7-(2-oxo-2<i>H</i>-chromen-3-yl)pyrazolo[1,5-<i>a</i>]pyrimidine derivatives. The structures of the synthesized compounds were confirmed using spectroscopic and analytical techniques, including FT-IR, <sup>1</sup>H, <sup>13</sup>C NMR, and high-resolution mass spectrometry (HRMS). Antibacterial and antibiofilm activities were evaluated against <i>Staphylococcus epidermidis</i> ATCC 35984 and <i>Pseudomonas aeruginosa</i> using MIC, MIC<sub>50</sub> assays, and biofilm formation inhibition studies. <b>Results and Discussion:</b> The synthesized coumarin–pyrazolo[1,5-<i>a</i>]pyrimidine (CPP) hybrids (<b>IVa–IVj</b>) were obtained in high yields (74–92%) within short reaction times (9–18 min). These compounds exhibited significant anti-adhesion and antibiofilm activities against both <i>S. epidermidis</i> and <i>P. aeruginosa</i>. All compounds were tested for their ability to inhibit bacterial cell adhesion to polystyrene surfaces. <b>Conclusions:</b> Hybrids (<b>IVd</b>) and (<b>IVe</b>) demonstrated outstanding and consistent antibiofilm activity against strong biofilm-forming strains, <i>S. epidermidis</i> ATCC 35984 and <i>P. aeruginosa</i>, indicating broad-spectrum efficacy at low concentrations.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 3","pages":"1306 - 1319"},"PeriodicalIF":1.7000,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Russian Journal of Bioorganic Chemistry","FirstCategoryId":"92","ListUrlMain":"https://link.springer.com/article/10.1134/S1068162024606360","RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Objective: This study aimed to synthesize a series of coumarin–pyrazolo[1,5-a]pyrimidine hybrid compounds and evaluate their potential antibacterial and antibiofilm activities. Methods: In our synthetic approach, a mixture of 3-acetylcoumarin (I) and N,N-dimethylformamide dimethyl acetal (DMF-DMA) was refluxed in toluene to afford the enaminone intermediate (II). Subsequent condensation with 3-aminopyrazoles in the presence of potassium hydrogen sulfate (KHSO4) yielded a series of 7-(2-oxo-2H-chromen-3-yl)pyrazolo[1,5-a]pyrimidine derivatives. The structures of the synthesized compounds were confirmed using spectroscopic and analytical techniques, including FT-IR, 1H, 13C NMR, and high-resolution mass spectrometry (HRMS). Antibacterial and antibiofilm activities were evaluated against Staphylococcus epidermidis ATCC 35984 and Pseudomonas aeruginosa using MIC, MIC50 assays, and biofilm formation inhibition studies. Results and Discussion: The synthesized coumarin–pyrazolo[1,5-a]pyrimidine (CPP) hybrids (IVa–IVj) were obtained in high yields (74–92%) within short reaction times (9–18 min). These compounds exhibited significant anti-adhesion and antibiofilm activities against both S. epidermidis and P. aeruginosa. All compounds were tested for their ability to inhibit bacterial cell adhesion to polystyrene surfaces. Conclusions: Hybrids (IVd) and (IVe) demonstrated outstanding and consistent antibiofilm activity against strong biofilm-forming strains, S. epidermidis ATCC 35984 and P. aeruginosa, indicating broad-spectrum efficacy at low concentrations.
期刊介绍:
Russian Journal of Bioorganic Chemistry publishes reviews and original experimental and theoretical studies on the structure, function, structure–activity relationships, and synthesis of biopolymers, such as proteins, nucleic acids, polysaccharides, mixed biopolymers, and their complexes, and low-molecular-weight biologically active compounds (peptides, sugars, lipids, antibiotics, etc.). The journal also covers selected aspects of neuro- and immunochemistry, biotechnology, and ecology.