Synthesis and preliminary structure-activity relationship study of 3-methylquinazolinone derivatives as EGFR inhibitors with enhanced antiproliferative activities against tumour cells
In this paper, a set of 3-methylquniazolinone derivatives were designed, synthesised, and studied the preliminary structure-activity relationship for antiproliferative activities. All target compounds performed significantly inhibitory effects against wild type epidermal growth factor receptor tyros...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2021-01-01
|
| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/14756366.2021.1933466 |
| _version_ | 1798016053004992512 |
|---|---|
| author | Yan Zhang Qin Wang Luolan Li Yi Le Li Liu Jing Yang Yongliang Li Guochen Bao Longjia Yan |
| author_facet | Yan Zhang Qin Wang Luolan Li Yi Le Li Liu Jing Yang Yongliang Li Guochen Bao Longjia Yan |
| author_sort | Yan Zhang |
| collection | DOAJ |
| description | In this paper, a set of 3-methylquniazolinone derivatives were designed, synthesised, and studied the preliminary structure-activity relationship for antiproliferative activities. All target compounds performed significantly inhibitory effects against wild type epidermal growth factor receptor tyrosine kinase (EGFRwt-TK) and tumour cells (A431, A549, MCF-7, and NCI-H1975). In particular, compound 4d 3-fluoro-N-(4-((3-methyl-4-oxo-3,4-dihydroquinazolin-2-yl)methoxy)phenyl)benzamide showed higher antiproliferative activities against all tumour cells than Gefitinib (IC50 of 3.48, 2.55, 0.87 and 6.42 μM, respectively). Furthermore, compound 4d could induce apoptosis of MCF-7 cells and arrest in G2/M phase at the tested concentration. Molecular docking and ADMET studies showed that compound 4d could closely form many hydrogen bonds with EGFRwt-TK. Therefore, compound 4d is potential to develop as novel anti-cancer drug. |
| first_indexed | 2024-04-11T15:44:33Z |
| format | Article |
| id | doaj.art-43ad163bbe804b18b2ac20efeb3d997a |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-04-11T15:44:33Z |
| publishDate | 2021-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-43ad163bbe804b18b2ac20efeb3d997a2022-12-22T04:15:37ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742021-01-013611205121610.1080/14756366.2021.19334661933466Synthesis and preliminary structure-activity relationship study of 3-methylquinazolinone derivatives as EGFR inhibitors with enhanced antiproliferative activities against tumour cellsYan Zhang0Qin Wang1Luolan Li2Yi Le3Li Liu4Jing Yang5Yongliang Li6Guochen Bao7Longjia Yan8School of Pharmaceutical Sciences, Guizhou UniversitySchool of Pharmaceutical Sciences, Guizhou UniversityState Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical UniversitySchool of Pharmaceutical Sciences, Guizhou UniversitySchool of Pharmaceutical Sciences, Guizhou UniversitySchool of Pharmaceutical Sciences, Guizhou UniversityFaculty of Light Industry and Chemical Engineering, Guangdong University of TechnologyInstitute for Biomedical Materials and Devices (IBMD), Faculty of Science, University of Technology SydneySchool of Pharmaceutical Sciences, Guizhou UniversityIn this paper, a set of 3-methylquniazolinone derivatives were designed, synthesised, and studied the preliminary structure-activity relationship for antiproliferative activities. All target compounds performed significantly inhibitory effects against wild type epidermal growth factor receptor tyrosine kinase (EGFRwt-TK) and tumour cells (A431, A549, MCF-7, and NCI-H1975). In particular, compound 4d 3-fluoro-N-(4-((3-methyl-4-oxo-3,4-dihydroquinazolin-2-yl)methoxy)phenyl)benzamide showed higher antiproliferative activities against all tumour cells than Gefitinib (IC50 of 3.48, 2.55, 0.87 and 6.42 μM, respectively). Furthermore, compound 4d could induce apoptosis of MCF-7 cells and arrest in G2/M phase at the tested concentration. Molecular docking and ADMET studies showed that compound 4d could closely form many hydrogen bonds with EGFRwt-TK. Therefore, compound 4d is potential to develop as novel anti-cancer drug.http://dx.doi.org/10.1080/14756366.2021.1933466quinazolinoneegfrkinase inhibitorstructure-activity relationshipantiproliferative |
| spellingShingle | Yan Zhang Qin Wang Luolan Li Yi Le Li Liu Jing Yang Yongliang Li Guochen Bao Longjia Yan Synthesis and preliminary structure-activity relationship study of 3-methylquinazolinone derivatives as EGFR inhibitors with enhanced antiproliferative activities against tumour cells Journal of Enzyme Inhibition and Medicinal Chemistry quinazolinone egfr kinase inhibitor structure-activity relationship antiproliferative |
| title | Synthesis and preliminary structure-activity relationship study of 3-methylquinazolinone derivatives as EGFR inhibitors with enhanced antiproliferative activities against tumour cells |
| title_full | Synthesis and preliminary structure-activity relationship study of 3-methylquinazolinone derivatives as EGFR inhibitors with enhanced antiproliferative activities against tumour cells |
| title_fullStr | Synthesis and preliminary structure-activity relationship study of 3-methylquinazolinone derivatives as EGFR inhibitors with enhanced antiproliferative activities against tumour cells |
| title_full_unstemmed | Synthesis and preliminary structure-activity relationship study of 3-methylquinazolinone derivatives as EGFR inhibitors with enhanced antiproliferative activities against tumour cells |
| title_short | Synthesis and preliminary structure-activity relationship study of 3-methylquinazolinone derivatives as EGFR inhibitors with enhanced antiproliferative activities against tumour cells |
| title_sort | synthesis and preliminary structure activity relationship study of 3 methylquinazolinone derivatives as egfr inhibitors with enhanced antiproliferative activities against tumour cells |
| topic | quinazolinone egfr kinase inhibitor structure-activity relationship antiproliferative |
| url | http://dx.doi.org/10.1080/14756366.2021.1933466 |
| work_keys_str_mv | AT yanzhang synthesisandpreliminarystructureactivityrelationshipstudyof3methylquinazolinonederivativesasegfrinhibitorswithenhancedantiproliferativeactivitiesagainsttumourcells AT qinwang synthesisandpreliminarystructureactivityrelationshipstudyof3methylquinazolinonederivativesasegfrinhibitorswithenhancedantiproliferativeactivitiesagainsttumourcells AT luolanli synthesisandpreliminarystructureactivityrelationshipstudyof3methylquinazolinonederivativesasegfrinhibitorswithenhancedantiproliferativeactivitiesagainsttumourcells AT yile synthesisandpreliminarystructureactivityrelationshipstudyof3methylquinazolinonederivativesasegfrinhibitorswithenhancedantiproliferativeactivitiesagainsttumourcells AT liliu synthesisandpreliminarystructureactivityrelationshipstudyof3methylquinazolinonederivativesasegfrinhibitorswithenhancedantiproliferativeactivitiesagainsttumourcells AT jingyang synthesisandpreliminarystructureactivityrelationshipstudyof3methylquinazolinonederivativesasegfrinhibitorswithenhancedantiproliferativeactivitiesagainsttumourcells AT yongliangli synthesisandpreliminarystructureactivityrelationshipstudyof3methylquinazolinonederivativesasegfrinhibitorswithenhancedantiproliferativeactivitiesagainsttumourcells AT guochenbao synthesisandpreliminarystructureactivityrelationshipstudyof3methylquinazolinonederivativesasegfrinhibitorswithenhancedantiproliferativeactivitiesagainsttumourcells AT longjiayan synthesisandpreliminarystructureactivityrelationshipstudyof3methylquinazolinonederivativesasegfrinhibitorswithenhancedantiproliferativeactivitiesagainsttumourcells |