Design, synthesis, anticancer properties, and molecular docking of imidazolone derivatives with lipophilic moiety
Abstract As part of an ongoing investigation into imidazolone derivatives with anticancer activities, herein we present the synthesis of a new series of imidazolones with various substituents, including lipophilic and hydrophilic. All synthesized imidazolones (3a–3g and 5a–5g) were characterized by...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-05-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-97478-2 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849688354806824960 |
|---|---|
| author | Oswa Fares Othman Hamed Mohyeddin Assali Avni Berisha Haythem Saadeh Bahia Abu Lail Omar Dagdag Abdullah Samaro Waseem Mansour Nidal Jaradat Saber Abu-Jabal |
| author_facet | Oswa Fares Othman Hamed Mohyeddin Assali Avni Berisha Haythem Saadeh Bahia Abu Lail Omar Dagdag Abdullah Samaro Waseem Mansour Nidal Jaradat Saber Abu-Jabal |
| author_sort | Oswa Fares |
| collection | DOAJ |
| description | Abstract As part of an ongoing investigation into imidazolone derivatives with anticancer activities, herein we present the synthesis of a new series of imidazolones with various substituents, including lipophilic and hydrophilic. All synthesized imidazolones (3a–3g and 5a–5g) were characterized by various spectroscopic methods (1H and 13C NMR, FT-IR, and mass spectrometry). The preparation was performed by condensation cyclization of vanillin-based oxazolones with various amines. The anticancer efficiencies of the prepared imidazolones were tested against four different cancer cell lines liver cancer cells (HepG2), cervical adenocarcinoma cells (HeLa), colon cancer cells (CaCo-2), breast cancer cells (MCF-7). Among the prepared imidazolones the one with dodecyl chain displayed excellent efficiency against the tested cancer cell lines with an IC50 value of 65.3 ± 3.2 µM against HepG2 and 20.02 ± 3.5 µM against MCF-7. Imidazolone 2d with amino alkyl moiety displayed an IC50 value of 35.6 ± 4.1 µM against HeLa cell and 24.6 ± 3.8 µM against CaCo-2 cell line. Imidazolone 5g with thiophene and pyridyl group showed the highest activity among all tested derivatives with IC50 value of 18.6 ± 2.3 µM and 5.9 ± 2.3 µM against HeLa and CaCo-2 cell lines, respectively. Imidazolone 5b with a chlorophenyl moiety displayed an IC50 value of 2.2 ± 0.7 µM and 5.5 ± 1.1 µM against HepG2 and Hela cell lines, respectively. The study used computational tools to assess the pharmacokinetics and antitumor potential of the synthesized imidazolone molecules with the highest activities. They were evaluated through ADME analysis and molecular docking. ADME properties confirm favorable drug-likeness under Lipinski’s guidelines, with molecular weights ranging from 357.43 (5d) to 468.65 g/mol (5f). Molecules 2g, 2f, and 5f show optimal hydrogen bonding, moderate bioavailability (0.55), and synthetic accessibility scores from 3.78 to 4.76. Docking studies with proteins 4MAN and 1HNJ highlight strong interactions for 2g, 2f, and 5f, with molecule 3g showing the best binding for 4MAN (− 52.13 kcal/mol) and 5f for 1HNJ (− 38.63 kcal/mol). These results identify 3g and 5f as promising candidates for targeted cancer therapy. |
| format | Article |
| id | doaj-art-2804aa508b6a499688652a9e2d808565 |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-2804aa508b6a499688652a9e2d8085652025-08-20T03:22:02ZengNature PortfolioScientific Reports2045-23222025-05-0115111610.1038/s41598-025-97478-2Design, synthesis, anticancer properties, and molecular docking of imidazolone derivatives with lipophilic moietyOswa Fares0Othman Hamed1Mohyeddin Assali2Avni Berisha3Haythem Saadeh4Bahia Abu Lail5Omar Dagdag6Abdullah Samaro7Waseem Mansour8Nidal Jaradat9Saber Abu-Jabal10Department of Chemistry, Faculty of Science, An-Najah National UniversityDepartment of Chemistry, Faculty of Science, An-Najah National UniversityDepartment of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National UniversityDepartment of Chemistry, Faculty of Natural and Mathematics Science, University of PrishtinaDepartment of Chemistry, Faculty of Science, The University of JordanDepartment of Chemistry, Faculty of Science, An-Najah National UniversityDepartment of Mechanical Engineering, Gachon UniversityDepartment of Biomedical Sciences, Faculty of Medicine and Health Sciences, An-Najah National UniversityDepartment of Chemistry, Faculty of Science, An-Najah National UniversityDepartment of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National UniversityDepartment of Chemistry, Faculty of Science, An-Najah National UniversityAbstract As part of an ongoing investigation into imidazolone derivatives with anticancer activities, herein we present the synthesis of a new series of imidazolones with various substituents, including lipophilic and hydrophilic. All synthesized imidazolones (3a–3g and 5a–5g) were characterized by various spectroscopic methods (1H and 13C NMR, FT-IR, and mass spectrometry). The preparation was performed by condensation cyclization of vanillin-based oxazolones with various amines. The anticancer efficiencies of the prepared imidazolones were tested against four different cancer cell lines liver cancer cells (HepG2), cervical adenocarcinoma cells (HeLa), colon cancer cells (CaCo-2), breast cancer cells (MCF-7). Among the prepared imidazolones the one with dodecyl chain displayed excellent efficiency against the tested cancer cell lines with an IC50 value of 65.3 ± 3.2 µM against HepG2 and 20.02 ± 3.5 µM against MCF-7. Imidazolone 2d with amino alkyl moiety displayed an IC50 value of 35.6 ± 4.1 µM against HeLa cell and 24.6 ± 3.8 µM against CaCo-2 cell line. Imidazolone 5g with thiophene and pyridyl group showed the highest activity among all tested derivatives with IC50 value of 18.6 ± 2.3 µM and 5.9 ± 2.3 µM against HeLa and CaCo-2 cell lines, respectively. Imidazolone 5b with a chlorophenyl moiety displayed an IC50 value of 2.2 ± 0.7 µM and 5.5 ± 1.1 µM against HepG2 and Hela cell lines, respectively. The study used computational tools to assess the pharmacokinetics and antitumor potential of the synthesized imidazolone molecules with the highest activities. They were evaluated through ADME analysis and molecular docking. ADME properties confirm favorable drug-likeness under Lipinski’s guidelines, with molecular weights ranging from 357.43 (5d) to 468.65 g/mol (5f). Molecules 2g, 2f, and 5f show optimal hydrogen bonding, moderate bioavailability (0.55), and synthetic accessibility scores from 3.78 to 4.76. Docking studies with proteins 4MAN and 1HNJ highlight strong interactions for 2g, 2f, and 5f, with molecule 3g showing the best binding for 4MAN (− 52.13 kcal/mol) and 5f for 1HNJ (− 38.63 kcal/mol). These results identify 3g and 5f as promising candidates for targeted cancer therapy.https://doi.org/10.1038/s41598-025-97478-2VanillinAntitumorLipophilicImidazoloneThiopheneADME |
| spellingShingle | Oswa Fares Othman Hamed Mohyeddin Assali Avni Berisha Haythem Saadeh Bahia Abu Lail Omar Dagdag Abdullah Samaro Waseem Mansour Nidal Jaradat Saber Abu-Jabal Design, synthesis, anticancer properties, and molecular docking of imidazolone derivatives with lipophilic moiety Scientific Reports Vanillin Antitumor Lipophilic Imidazolone Thiophene ADME |
| title | Design, synthesis, anticancer properties, and molecular docking of imidazolone derivatives with lipophilic moiety |
| title_full | Design, synthesis, anticancer properties, and molecular docking of imidazolone derivatives with lipophilic moiety |
| title_fullStr | Design, synthesis, anticancer properties, and molecular docking of imidazolone derivatives with lipophilic moiety |
| title_full_unstemmed | Design, synthesis, anticancer properties, and molecular docking of imidazolone derivatives with lipophilic moiety |
| title_short | Design, synthesis, anticancer properties, and molecular docking of imidazolone derivatives with lipophilic moiety |
| title_sort | design synthesis anticancer properties and molecular docking of imidazolone derivatives with lipophilic moiety |
| topic | Vanillin Antitumor Lipophilic Imidazolone Thiophene ADME |
| url | https://doi.org/10.1038/s41598-025-97478-2 |
| work_keys_str_mv | AT oswafares designsynthesisanticancerpropertiesandmoleculardockingofimidazolonederivativeswithlipophilicmoiety AT othmanhamed designsynthesisanticancerpropertiesandmoleculardockingofimidazolonederivativeswithlipophilicmoiety AT mohyeddinassali designsynthesisanticancerpropertiesandmoleculardockingofimidazolonederivativeswithlipophilicmoiety AT avniberisha designsynthesisanticancerpropertiesandmoleculardockingofimidazolonederivativeswithlipophilicmoiety AT haythemsaadeh designsynthesisanticancerpropertiesandmoleculardockingofimidazolonederivativeswithlipophilicmoiety AT bahiaabulail designsynthesisanticancerpropertiesandmoleculardockingofimidazolonederivativeswithlipophilicmoiety AT omardagdag designsynthesisanticancerpropertiesandmoleculardockingofimidazolonederivativeswithlipophilicmoiety AT abdullahsamaro designsynthesisanticancerpropertiesandmoleculardockingofimidazolonederivativeswithlipophilicmoiety AT waseemmansour designsynthesisanticancerpropertiesandmoleculardockingofimidazolonederivativeswithlipophilicmoiety AT nidaljaradat designsynthesisanticancerpropertiesandmoleculardockingofimidazolonederivativeswithlipophilicmoiety AT saberabujabal designsynthesisanticancerpropertiesandmoleculardockingofimidazolonederivativeswithlipophilicmoiety |