Design, synthesis, and study of novel phenethyl-based antitumor phospholipids downregulating p38 mitogen-activated protein kinase
AbstractPhenethyl-based edelfosine-analogs with saturated, monounsaturated, or polyunsaturated alkoxy substituents on phenyl ring were designed as novel antitumor lipids modulating p38 MAPK. Evaluation of the synthesised compounds against nine panels of diverse cancer cells presented saturated and m...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2023.2217695 |
| _version_ | 1797400971924471808 |
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| author | Ahmed H. E. Hassan Yeon Il Oh Chae Hyeon Lee Yeon Ju Kim Soo Bin Cho Md. Maqusood Alam Sang-Eun Park Kyung-Sook Chung Kyung-Tae Lee Yong Sup Lee |
| author_facet | Ahmed H. E. Hassan Yeon Il Oh Chae Hyeon Lee Yeon Ju Kim Soo Bin Cho Md. Maqusood Alam Sang-Eun Park Kyung-Sook Chung Kyung-Tae Lee Yong Sup Lee |
| author_sort | Ahmed H. E. Hassan |
| collection | DOAJ |
| description | AbstractPhenethyl-based edelfosine-analogs with saturated, monounsaturated, or polyunsaturated alkoxy substituents on phenyl ring were designed as novel antitumor lipids modulating p38 MAPK. Evaluation of the synthesised compounds against nine panels of diverse cancer cells presented saturated and monounsaturated alkoxy-substituted derivatives as the most active than other derivatives. In addition, ortho-substituted compounds were more active than meta- or ortho-substituted compounds. They were potential anticancer agents against blood, lung, colon, CNS, ovary, renal, and prostate cancers but not against skin nor breast cancers. Compounds, 1b and 1a emerged as the most potential anticancer agents. Assessment of compound 1b impact on p38 MAPK and AKT confirmed it as an inhibitor of p38 MAPK but not AKT. In silico study suggested compounds 1b and 1a as possible binders to the lipid binding pocket of p38 MAPK. Overall, compounds 1b and 1a as novel broad spectrum antitumor lipids modulating activity of p38 MAPK for further development. |
| first_indexed | 2024-03-09T02:03:11Z |
| format | Article |
| id | doaj.art-c593553338f64ac58bc7690f590ec50e |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-03-09T02:03:11Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-c593553338f64ac58bc7690f590ec50e2023-12-08T03:24:21ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742023-12-0138110.1080/14756366.2023.2217695Design, synthesis, and study of novel phenethyl-based antitumor phospholipids downregulating p38 mitogen-activated protein kinaseAhmed H. E. Hassan0Yeon Il Oh1Chae Hyeon Lee2Yeon Ju Kim3Soo Bin Cho4Md. Maqusood Alam5Sang-Eun Park6Kyung-Sook Chung7Kyung-Tae Lee8Yong Sup Lee9Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, EgyptDepartment of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul, Republic of KoreaDepartment of Fundamental Pharmaceutical Sciences, Kyung Hee University, Seoul, Republic of KoreaDepartment of Fundamental Pharmaceutical Sciences, Kyung Hee University, Seoul, Republic of KoreaDepartment of Fundamental Pharmaceutical Sciences, Kyung Hee University, Seoul, Republic of KoreaDepartment of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul, Republic of KoreaDepartment of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul, Republic of KoreaDepartment of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul, Republic of KoreaDepartment of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul, Republic of KoreaMedicinal Chemistry Laboratory, Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul, Republic of KoreaAbstractPhenethyl-based edelfosine-analogs with saturated, monounsaturated, or polyunsaturated alkoxy substituents on phenyl ring were designed as novel antitumor lipids modulating p38 MAPK. Evaluation of the synthesised compounds against nine panels of diverse cancer cells presented saturated and monounsaturated alkoxy-substituted derivatives as the most active than other derivatives. In addition, ortho-substituted compounds were more active than meta- or ortho-substituted compounds. They were potential anticancer agents against blood, lung, colon, CNS, ovary, renal, and prostate cancers but not against skin nor breast cancers. Compounds, 1b and 1a emerged as the most potential anticancer agents. Assessment of compound 1b impact on p38 MAPK and AKT confirmed it as an inhibitor of p38 MAPK but not AKT. In silico study suggested compounds 1b and 1a as possible binders to the lipid binding pocket of p38 MAPK. Overall, compounds 1b and 1a as novel broad spectrum antitumor lipids modulating activity of p38 MAPK for further development.https://www.tandfonline.com/doi/10.1080/14756366.2023.2217695Antitumor lipidsPhospholipidsCancerp38 MAPK |
| spellingShingle | Ahmed H. E. Hassan Yeon Il Oh Chae Hyeon Lee Yeon Ju Kim Soo Bin Cho Md. Maqusood Alam Sang-Eun Park Kyung-Sook Chung Kyung-Tae Lee Yong Sup Lee Design, synthesis, and study of novel phenethyl-based antitumor phospholipids downregulating p38 mitogen-activated protein kinase Journal of Enzyme Inhibition and Medicinal Chemistry Antitumor lipids Phospholipids Cancer p38 MAPK |
| title | Design, synthesis, and study of novel phenethyl-based antitumor phospholipids downregulating p38 mitogen-activated protein kinase |
| title_full | Design, synthesis, and study of novel phenethyl-based antitumor phospholipids downregulating p38 mitogen-activated protein kinase |
| title_fullStr | Design, synthesis, and study of novel phenethyl-based antitumor phospholipids downregulating p38 mitogen-activated protein kinase |
| title_full_unstemmed | Design, synthesis, and study of novel phenethyl-based antitumor phospholipids downregulating p38 mitogen-activated protein kinase |
| title_short | Design, synthesis, and study of novel phenethyl-based antitumor phospholipids downregulating p38 mitogen-activated protein kinase |
| title_sort | design synthesis and study of novel phenethyl based antitumor phospholipids downregulating p38 mitogen activated protein kinase |
| topic | Antitumor lipids Phospholipids Cancer p38 MAPK |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2023.2217695 |
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