Solid-phase synthesis and cytotoxic evaluation of novel pyridinium bromides
Abstract A series of amide-based mono and dimeric pyridinium bromides were synthesized using conventional and microwave-assisted solvent-free methods. The quaternization reactions of m-xylene dibromide and 4-nitrobenzylbromide with amide-based substituted pyridine proceeded efficiently, whereas 1,6-...
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Nature Portfolio
2025-03-01
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| Online Access: | https://doi.org/10.1038/s41598-025-92672-8 |
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| author | Sadaiyan Govindaraj Kilivelu Ganesan Perumal Elumalai Rajanathadurai Jeevitha Jospin Sindya Subramani Annadurai Shiek S. S. J. Ahmed Mudassar Shahid |
| author_facet | Sadaiyan Govindaraj Kilivelu Ganesan Perumal Elumalai Rajanathadurai Jeevitha Jospin Sindya Subramani Annadurai Shiek S. S. J. Ahmed Mudassar Shahid |
| author_sort | Sadaiyan Govindaraj |
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| description | Abstract A series of amide-based mono and dimeric pyridinium bromides were synthesized using conventional and microwave-assisted solvent-free methods. The quaternization reactions of m-xylene dibromide and 4-nitrobenzylbromide with amide-based substituted pyridine proceeded efficiently, whereas 1,6-dibromohexane required reflux conditions. A comparative analysis of the solvent-free microwave-assisted reactions revealed a significant reduction in reaction time (up to 20-fold) and increased yields, accompanied by simplified work-up procedures. Notably, these reactions exhibited 100% atom economy and generated no environmental waste. The cytotoxic effects of the synthesized compounds were assessed using the MTT assay, nuclear staining, and Real Time-Polymerase Chain Reaction (PCR) on the lung cancer cell line (A-549).Molecular docking studies were performed to investigate the interaction and binding of B-Raf kinase inhibitors with the amide-based mono and dimeric pyridinium bromides. Furthermore, the toxicity of the drug molecules was assessed using the BOILED-Egg plot at the central nervous system. |
| format | Article |
| id | doaj-art-5a45845065014d419edf3ec57642ec67 |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-5a45845065014d419edf3ec57642ec672025-08-20T02:49:30ZengNature PortfolioScientific Reports2045-23222025-03-0115111810.1038/s41598-025-92672-8Solid-phase synthesis and cytotoxic evaluation of novel pyridinium bromidesSadaiyan Govindaraj0Kilivelu Ganesan1Perumal Elumalai2Rajanathadurai Jeevitha3Jospin Sindya4Subramani Annadurai5Shiek S. S. J. Ahmed6Mudassar Shahid7Department of Chemistry, Presidency CollegeDepartment of Chemistry, Presidency CollegeCancer Genomics Lab, Department of Biochemistry, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical SciencesCancer Genomics Lab, Department of Biochemistry, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical SciencesCancer Genomics Lab, Department of Biochemistry, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical SciencesDepartment of Biochemistry, Dwaraka Doss Goverdhan Doss Vaishnav CollegeDrug Discovery and Multi-omics Laboratory, Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute, Chettinad Academy of Research and EducationDepartment of Pharmaceutics, College of Pharmacy, King Saud UniversityAbstract A series of amide-based mono and dimeric pyridinium bromides were synthesized using conventional and microwave-assisted solvent-free methods. The quaternization reactions of m-xylene dibromide and 4-nitrobenzylbromide with amide-based substituted pyridine proceeded efficiently, whereas 1,6-dibromohexane required reflux conditions. A comparative analysis of the solvent-free microwave-assisted reactions revealed a significant reduction in reaction time (up to 20-fold) and increased yields, accompanied by simplified work-up procedures. Notably, these reactions exhibited 100% atom economy and generated no environmental waste. The cytotoxic effects of the synthesized compounds were assessed using the MTT assay, nuclear staining, and Real Time-Polymerase Chain Reaction (PCR) on the lung cancer cell line (A-549).Molecular docking studies were performed to investigate the interaction and binding of B-Raf kinase inhibitors with the amide-based mono and dimeric pyridinium bromides. Furthermore, the toxicity of the drug molecules was assessed using the BOILED-Egg plot at the central nervous system.https://doi.org/10.1038/s41598-025-92672-8Amide-based pyridiniumSolvent free reactionAtom economyCytotoxicMolecular dockingBOILED-Egg plot |
| spellingShingle | Sadaiyan Govindaraj Kilivelu Ganesan Perumal Elumalai Rajanathadurai Jeevitha Jospin Sindya Subramani Annadurai Shiek S. S. J. Ahmed Mudassar Shahid Solid-phase synthesis and cytotoxic evaluation of novel pyridinium bromides Scientific Reports Amide-based pyridinium Solvent free reaction Atom economy Cytotoxic Molecular docking BOILED-Egg plot |
| title | Solid-phase synthesis and cytotoxic evaluation of novel pyridinium bromides |
| title_full | Solid-phase synthesis and cytotoxic evaluation of novel pyridinium bromides |
| title_fullStr | Solid-phase synthesis and cytotoxic evaluation of novel pyridinium bromides |
| title_full_unstemmed | Solid-phase synthesis and cytotoxic evaluation of novel pyridinium bromides |
| title_short | Solid-phase synthesis and cytotoxic evaluation of novel pyridinium bromides |
| title_sort | solid phase synthesis and cytotoxic evaluation of novel pyridinium bromides |
| topic | Amide-based pyridinium Solvent free reaction Atom economy Cytotoxic Molecular docking BOILED-Egg plot |
| url | https://doi.org/10.1038/s41598-025-92672-8 |
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