Molecular and metabolic alterations of 2,3-dihydroquinazolin-4(1H)-one derivatives in prostate cancer cell lines
Abstract Prostate cancer (PC) is the second most common tumor in males worldwide. The lack of effective medication and the development of multidrug resistance towards current chemotherapeutic agents urge the need to discover novel compounds and therapeutic targets for PC. Herein, seven synthesized 2...
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| Format: | Article |
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Nature Portfolio
2022-12-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-26148-4 |
| _version_ | 1828164672405110784 |
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| author | Lina A. Dahabiyeh Wafa Hourani Wesam Darwish Farah Hudaib Bashaer Abu-Irmaileh Pran Kishore Deb Katharigatta N. Venugopala Viresh Mohanlall Rana Abu-Dahab Mohammad H. Semreen Yasser Bustanji |
| author_facet | Lina A. Dahabiyeh Wafa Hourani Wesam Darwish Farah Hudaib Bashaer Abu-Irmaileh Pran Kishore Deb Katharigatta N. Venugopala Viresh Mohanlall Rana Abu-Dahab Mohammad H. Semreen Yasser Bustanji |
| author_sort | Lina A. Dahabiyeh |
| collection | DOAJ |
| description | Abstract Prostate cancer (PC) is the second most common tumor in males worldwide. The lack of effective medication and the development of multidrug resistance towards current chemotherapeutic agents urge the need to discover novel compounds and therapeutic targets for PC. Herein, seven synthesized 2,3-dihydroquinazolin-4(1H)-one analogues were evaluated for their anticancer activity against PC3 and DU145 cancer cell lines using MTT, scratch-wound healing, adhesion and invasion assays. Besides, a liquid chromatography mass spectrometry (LC–MS)-based metabolomics approach was followed to identify the biochemical pathways altered in DU145 cancer cells upon exposure to dihydroquinazolin derivatives. The seven compounds showed sufficient cytotoxicity and significantly suppressed DU145 and PC3 migration after 48 and 72 h. C2 and C5 had the most potent effect with IC50 < 15 µM and significantly inhibited PC cell adhesion and invasion. Metabolomics revealed that C5 disturbed the level of metabolites involved in essential processes for cancer cell proliferation, progression and growth including energy production, redox homeostasis, amino acids and polyamine metabolisms and choline phospholipid metabolism. The data presented herein highlighted the importance of these compounds as potential anticancer agents particularly C5, and pointed to the promising role of metabolomics as a new analytical approach to investigate the antiproliferative activity of synthesized compounds and identify new therapeutic targets. |
| first_indexed | 2024-04-12T01:30:19Z |
| format | Article |
| id | doaj.art-11964cc1bfd040b7964a4241fae7f207 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-12T01:30:19Z |
| publishDate | 2022-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-11964cc1bfd040b7964a4241fae7f2072022-12-22T03:53:31ZengNature PortfolioScientific Reports2045-23222022-12-0112111710.1038/s41598-022-26148-4Molecular and metabolic alterations of 2,3-dihydroquinazolin-4(1H)-one derivatives in prostate cancer cell linesLina A. Dahabiyeh0Wafa Hourani1Wesam Darwish2Farah Hudaib3Bashaer Abu-Irmaileh4Pran Kishore Deb5Katharigatta N. Venugopala6Viresh Mohanlall7Rana Abu-Dahab8Mohammad H. Semreen9Yasser Bustanji10Department of Pharmaceutical Sciences, School of Pharmacy, The University of JordanDepartment of Pharmaceutical Sciences, Faculty of Pharmacy, Philadelphia UniversityDepartment of Pharmaceutical Sciences, School of Pharmacy, The University of JordanDepatment of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, the Hashemite UniversityHamdi Mango Center for Scientific Research, The University of JordanDepartment of Pharmaceutical Sciences, Faculty of Pharmacy, Philadelphia UniversityDepartment of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal UniversityDepartment of Biotechnology and Food Science, Faculty of Applied Sciences, Durban University of TechnologyDepartment of Biopharmaceutics and Clinical Pharmacy, School of Pharmacy, The University of JordanDepartment of Medicinal Chemistry, College of Pharmacy, University of SharjahDepartment of Basic Medical Sciences, College of Medicine, University of SharjahAbstract Prostate cancer (PC) is the second most common tumor in males worldwide. The lack of effective medication and the development of multidrug resistance towards current chemotherapeutic agents urge the need to discover novel compounds and therapeutic targets for PC. Herein, seven synthesized 2,3-dihydroquinazolin-4(1H)-one analogues were evaluated for their anticancer activity against PC3 and DU145 cancer cell lines using MTT, scratch-wound healing, adhesion and invasion assays. Besides, a liquid chromatography mass spectrometry (LC–MS)-based metabolomics approach was followed to identify the biochemical pathways altered in DU145 cancer cells upon exposure to dihydroquinazolin derivatives. The seven compounds showed sufficient cytotoxicity and significantly suppressed DU145 and PC3 migration after 48 and 72 h. C2 and C5 had the most potent effect with IC50 < 15 µM and significantly inhibited PC cell adhesion and invasion. Metabolomics revealed that C5 disturbed the level of metabolites involved in essential processes for cancer cell proliferation, progression and growth including energy production, redox homeostasis, amino acids and polyamine metabolisms and choline phospholipid metabolism. The data presented herein highlighted the importance of these compounds as potential anticancer agents particularly C5, and pointed to the promising role of metabolomics as a new analytical approach to investigate the antiproliferative activity of synthesized compounds and identify new therapeutic targets.https://doi.org/10.1038/s41598-022-26148-4 |
| spellingShingle | Lina A. Dahabiyeh Wafa Hourani Wesam Darwish Farah Hudaib Bashaer Abu-Irmaileh Pran Kishore Deb Katharigatta N. Venugopala Viresh Mohanlall Rana Abu-Dahab Mohammad H. Semreen Yasser Bustanji Molecular and metabolic alterations of 2,3-dihydroquinazolin-4(1H)-one derivatives in prostate cancer cell lines Scientific Reports |
| title | Molecular and metabolic alterations of 2,3-dihydroquinazolin-4(1H)-one derivatives in prostate cancer cell lines |
| title_full | Molecular and metabolic alterations of 2,3-dihydroquinazolin-4(1H)-one derivatives in prostate cancer cell lines |
| title_fullStr | Molecular and metabolic alterations of 2,3-dihydroquinazolin-4(1H)-one derivatives in prostate cancer cell lines |
| title_full_unstemmed | Molecular and metabolic alterations of 2,3-dihydroquinazolin-4(1H)-one derivatives in prostate cancer cell lines |
| title_short | Molecular and metabolic alterations of 2,3-dihydroquinazolin-4(1H)-one derivatives in prostate cancer cell lines |
| title_sort | molecular and metabolic alterations of 2 3 dihydroquinazolin 4 1h one derivatives in prostate cancer cell lines |
| url | https://doi.org/10.1038/s41598-022-26148-4 |
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