Synthesis, crystal structure, DFT calculations, in-vitro and in-silico studies of novel chromone-isoxazoline conjugates as antibacterial and anti-inflammatory agents
Abstract In this study, we report the synthesis and biological evaluation of a novel series of chromone-isoxazoline hybrids. These conjugates were successfully synthesized through N-alkylation and 1,3-dipolar cycloaddition reactions, and their structures were determined by spectroscopic analysis (1H...
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Nature Portfolio
2025-08-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-11182-9 |
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| author | Rachid Bouzammit Naoufal El Hachlafi Mohamed El fadili Mouna El Khabchi Youssra Kanzouai Rachid Salghi Mohammed M. Alanazi Mohammed Chalkha Alexandra M. Pop Emese Gal Luiza Ioana Gaina Ghali Al Houari |
| author_facet | Rachid Bouzammit Naoufal El Hachlafi Mohamed El fadili Mouna El Khabchi Youssra Kanzouai Rachid Salghi Mohammed M. Alanazi Mohammed Chalkha Alexandra M. Pop Emese Gal Luiza Ioana Gaina Ghali Al Houari |
| author_sort | Rachid Bouzammit |
| collection | DOAJ |
| description | Abstract In this study, we report the synthesis and biological evaluation of a novel series of chromone-isoxazoline hybrids. These conjugates were successfully synthesized through N-alkylation and 1,3-dipolar cycloaddition reactions, and their structures were determined by spectroscopic analysis (1H and 13C-NMR), mass spectrometry (MS), and X-ray diffraction (XRD) analysis. The XRD study showed that the compound crystallizes in the monoclinic system (S.G: P21/c). The antibacterial activity of the hybrid compounds was assessed in vitro against the Gram-positive bacterium Bacillus subtilis ATCC 6633 and three Gram-negative bacteria (Klebsiella aerogenes ATCC 13,048, Escherichia coli ATCC 27,853, and Salmonella enterica serotype Typhi) using the disk diffusion technique, MIC and MBC assays. The results showed that some tested compounds exhibited promising efficacy compared to the standard antibiotic chloramphenicol, underscoring their potential as antibacterial agents. These results were further validated through the determination of MIC and MBC values using the microdilution test, which showed a strong bactericidal effect of some compounds against the selected bacterial strains. Additionally, the studied compounds showed good anti-inflammatory potential by effectively inhibiting 5-LOX enzyme, with compound 5e was the most active, presenting an IC50 value of 0.951 ± 0.02 mg/mL. These in vitro results were complemented by in silico studies, including ADMET (absorption, distribution, metabolism, excretion, and toxicity) predictions and molecular docking simulations. The docking analyses provided insights into the inhibition mechanisms, revealing specific interactions of the synthesized molecules with target proteins relevant to both their antibacterial and anti-inflammatory activities. Finally, density functional theory (DFT)-based calculations were performed to optimize the geometric structures and analyze the structural and electronic properties of the hybrid compounds. While the results are promising, further optimization of compound potency is necessary to enhance their therapeutic potential. |
| format | Article |
| id | doaj-art-9c5bf7f79af04a9bbec35f49907a7999 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-9c5bf7f79af04a9bbec35f49907a79992025-08-24T11:26:20ZengNature PortfolioScientific Reports2045-23222025-08-0115112510.1038/s41598-025-11182-9Synthesis, crystal structure, DFT calculations, in-vitro and in-silico studies of novel chromone-isoxazoline conjugates as antibacterial and anti-inflammatory agentsRachid Bouzammit0Naoufal El Hachlafi1Mohamed El fadili2Mouna El Khabchi3Youssra Kanzouai4Rachid Salghi5Mohammed M. Alanazi6Mohammed Chalkha7Alexandra M. Pop8Emese Gal9Luiza Ioana Gaina10Ghali Al Houari11Engineering Laboratory of Organometallic and Molecular Materials and Environment, Faculty of Sciences Dhar EL Mahraz, University Sidi Mohamed Ben AbdellahFaculty of Sciences and Technologies, Sidi Mohamed Ben Abdellah UniversityLIMAS Laboratory, Chemistry Department, Faculty of Sciences Dhar EL Mahraz, Sidi Mohamed Ben Abdellah UniversitySchool of Science and Engineering, Al Akhawayn University in IfraneEngineering Laboratory of Organometallic and Molecular Materials and Environment, Faculty of Sciences Dhar EL Mahraz, University Sidi Mohamed Ben AbdellahLaboratory of Applied Chemistry and Environment, ENSA, University Ibn ZohrDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud UniversityEngineering Laboratory of Organometallic and Molecular Materials and Environment, Faculty of Sciences Dhar EL Mahraz, University Sidi Mohamed Ben AbdellahFaculty of Chemistry and Chemical Engineering, Babes-Bolyai UniversityFaculty of Chemistry and Chemical Engineering, Research Center on Fundamental and Applied Heterochemistry, Babeş-Bolyai UniversityFaculty of Chemistry and Chemical Engineering, Research Center on Fundamental and Applied Heterochemistry, Babeş-Bolyai UniversityEngineering Laboratory of Organometallic and Molecular Materials and Environment, Faculty of Sciences Dhar EL Mahraz, University Sidi Mohamed Ben AbdellahAbstract In this study, we report the synthesis and biological evaluation of a novel series of chromone-isoxazoline hybrids. These conjugates were successfully synthesized through N-alkylation and 1,3-dipolar cycloaddition reactions, and their structures were determined by spectroscopic analysis (1H and 13C-NMR), mass spectrometry (MS), and X-ray diffraction (XRD) analysis. The XRD study showed that the compound crystallizes in the monoclinic system (S.G: P21/c). The antibacterial activity of the hybrid compounds was assessed in vitro against the Gram-positive bacterium Bacillus subtilis ATCC 6633 and three Gram-negative bacteria (Klebsiella aerogenes ATCC 13,048, Escherichia coli ATCC 27,853, and Salmonella enterica serotype Typhi) using the disk diffusion technique, MIC and MBC assays. The results showed that some tested compounds exhibited promising efficacy compared to the standard antibiotic chloramphenicol, underscoring their potential as antibacterial agents. These results were further validated through the determination of MIC and MBC values using the microdilution test, which showed a strong bactericidal effect of some compounds against the selected bacterial strains. Additionally, the studied compounds showed good anti-inflammatory potential by effectively inhibiting 5-LOX enzyme, with compound 5e was the most active, presenting an IC50 value of 0.951 ± 0.02 mg/mL. These in vitro results were complemented by in silico studies, including ADMET (absorption, distribution, metabolism, excretion, and toxicity) predictions and molecular docking simulations. The docking analyses provided insights into the inhibition mechanisms, revealing specific interactions of the synthesized molecules with target proteins relevant to both their antibacterial and anti-inflammatory activities. Finally, density functional theory (DFT)-based calculations were performed to optimize the geometric structures and analyze the structural and electronic properties of the hybrid compounds. While the results are promising, further optimization of compound potency is necessary to enhance their therapeutic potential.https://doi.org/10.1038/s41598-025-11182-9SynthesisX-ray diffractionChromone-isoxazolineAntibacterial activityAnti-inflammatory activityMolecular docking and DFT study |
| spellingShingle | Rachid Bouzammit Naoufal El Hachlafi Mohamed El fadili Mouna El Khabchi Youssra Kanzouai Rachid Salghi Mohammed M. Alanazi Mohammed Chalkha Alexandra M. Pop Emese Gal Luiza Ioana Gaina Ghali Al Houari Synthesis, crystal structure, DFT calculations, in-vitro and in-silico studies of novel chromone-isoxazoline conjugates as antibacterial and anti-inflammatory agents Scientific Reports Synthesis X-ray diffraction Chromone-isoxazoline Antibacterial activity Anti-inflammatory activity Molecular docking and DFT study |
| title | Synthesis, crystal structure, DFT calculations, in-vitro and in-silico studies of novel chromone-isoxazoline conjugates as antibacterial and anti-inflammatory agents |
| title_full | Synthesis, crystal structure, DFT calculations, in-vitro and in-silico studies of novel chromone-isoxazoline conjugates as antibacterial and anti-inflammatory agents |
| title_fullStr | Synthesis, crystal structure, DFT calculations, in-vitro and in-silico studies of novel chromone-isoxazoline conjugates as antibacterial and anti-inflammatory agents |
| title_full_unstemmed | Synthesis, crystal structure, DFT calculations, in-vitro and in-silico studies of novel chromone-isoxazoline conjugates as antibacterial and anti-inflammatory agents |
| title_short | Synthesis, crystal structure, DFT calculations, in-vitro and in-silico studies of novel chromone-isoxazoline conjugates as antibacterial and anti-inflammatory agents |
| title_sort | synthesis crystal structure dft calculations in vitro and in silico studies of novel chromone isoxazoline conjugates as antibacterial and anti inflammatory agents |
| topic | Synthesis X-ray diffraction Chromone-isoxazoline Antibacterial activity Anti-inflammatory activity Molecular docking and DFT study |
| url | https://doi.org/10.1038/s41598-025-11182-9 |
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