{"title":"A New 1,2,3-Triazole-Based Benzooxepines: Design, Synthesis, and In Silico Docking, ADME-T and Antimicrobial Evaluation","authors":"Sateesh Kuna, Madhusudhan Patlola, Srinu Bhoomandla, Sreedhar Pandiri, Premalatha Akarapu, Tejeswara Rao Allaka","doi":"10.1134/S1070363225603035","DOIUrl":null,"url":null,"abstract":"<p>In this work, the molecular hybridization approach was employed to design a series of benzooxepine linked to 1,2,3-triazolyl chalcone structures, and the prepared molecules were synthesized using a click chemistry protocol. Several spectral approaches, including infrared, <sup>1</sup>H NMR, <sup>13</sup>C NMR, IR and HRMS spectrometric analysis, were used to determine the product structures. Three of the investigated compounds <i>p</i>-fluorophenyl, and <i>o</i>-nitrophenyl substituted chalcones shown remarkable antibacterial susceptibilities against the tested strain of <i>S. aureus</i>, with MICs (minimum inhibitory concentrations) ranging from 4.26±0.52 to 6.19±0.11 μg/mL. When compared to clotrimazole (MIC = 6.10±0.81 μg/mL), the prepared scaffolds showed better antifungal activity against <i>C. albicans</i>, with MIC values ranging from 4.45±0.14 to 38.79±1.32 μg/mL. Furthermore, a small number of derivatives with MIC ranges of 3.01 to 5.12 μM showed comparable antitubercular activity against the <i>H</i><sub>37</sub><i>Rv</i> strain. Docking experiments verified one of the ligand abilities to build a stable compound on the CYP51 active site from <i>M. TB</i> (PDB code: 1EA1). The chalcone-1,2,3-triazole hybrids molecular properties, bioactivity scores, toxicity assessment, and ADME were also evaluated. Furthermore, In-silico ADME, molecular docking revealed that the active compounds have substantial potential as candidates for the development of novel antitubercular medicines.</p>","PeriodicalId":761,"journal":{"name":"Russian Journal of General Chemistry","volume":"95 9","pages":"2601 - 2615"},"PeriodicalIF":0.8000,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Russian Journal of General Chemistry","FirstCategoryId":"92","ListUrlMain":"https://link.springer.com/article/10.1134/S1070363225603035","RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
In this work, the molecular hybridization approach was employed to design a series of benzooxepine linked to 1,2,3-triazolyl chalcone structures, and the prepared molecules were synthesized using a click chemistry protocol. Several spectral approaches, including infrared, 1H NMR, 13C NMR, IR and HRMS spectrometric analysis, were used to determine the product structures. Three of the investigated compounds p-fluorophenyl, and o-nitrophenyl substituted chalcones shown remarkable antibacterial susceptibilities against the tested strain of S. aureus, with MICs (minimum inhibitory concentrations) ranging from 4.26±0.52 to 6.19±0.11 μg/mL. When compared to clotrimazole (MIC = 6.10±0.81 μg/mL), the prepared scaffolds showed better antifungal activity against C. albicans, with MIC values ranging from 4.45±0.14 to 38.79±1.32 μg/mL. Furthermore, a small number of derivatives with MIC ranges of 3.01 to 5.12 μM showed comparable antitubercular activity against the H37Rv strain. Docking experiments verified one of the ligand abilities to build a stable compound on the CYP51 active site from M. TB (PDB code: 1EA1). The chalcone-1,2,3-triazole hybrids molecular properties, bioactivity scores, toxicity assessment, and ADME were also evaluated. Furthermore, In-silico ADME, molecular docking revealed that the active compounds have substantial potential as candidates for the development of novel antitubercular medicines.
期刊介绍:
Russian Journal of General Chemistry is a journal that covers many problems that are of general interest to the whole community of chemists. The journal is the successor to Russia’s first chemical journal, Zhurnal Russkogo Khimicheskogo Obshchestva (Journal of the Russian Chemical Society ) founded in 1869 to cover all aspects of chemistry. Now the journal is focused on the interdisciplinary areas of chemistry (organometallics, organometalloids, organoinorganic complexes, mechanochemistry, nanochemistry, etc.), new achievements and long-term results in the field. The journal publishes reviews, current scientific papers, letters to the editor, and discussion papers.