In silico design of novel dihydropteridone derivatives with oxadiazoles as potent inhibitors of MCF-7 breast cancer cells
IntroductionPharmaceutical treatment protocols or combination therapies based on chemical compounds make it possible to target cancer cells, which can be complicated by several factors, including their resistance to bioactive compounds and the potential for drugs to damage certain healthy cells.Meth...
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Frontiers Media S.A.
2025-07-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fchem.2025.1590593/full |
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| author | Mourad Aloui Mohamed El fadili Mohammed Er-rajy Somdutt Mujwar Hatem A. Abuelizz Sara Er-rahmani Elhalaoui Menana |
| author_facet | Mourad Aloui Mohamed El fadili Mohammed Er-rajy Somdutt Mujwar Hatem A. Abuelizz Sara Er-rahmani Elhalaoui Menana |
| author_sort | Mourad Aloui |
| collection | DOAJ |
| description | IntroductionPharmaceutical treatment protocols or combination therapies based on chemical compounds make it possible to target cancer cells, which can be complicated by several factors, including their resistance to bioactive compounds and the potential for drugs to damage certain healthy cells.MethodsThis project was designed to assess the structural relationship between new dihydropteridone-derived compounds bearing an oxadiazole moiety and their corresponding cytotoxicity against breast cancer, using computational chemistry tools. The aim of this research is to better understand how compound properties influence their activity and to understand the underlying mechanisms, which could then be integrated into the anticancer drug design process with a view to recommending new optimized compounds likely to have the desired activity.Results and discussionsThe results show that the predicted molecules possess enhanced selective cytotoxic inhibitory activity against breast cancer cells (MCF-7). Guided by these analyses, we designed five novel dihydropteridone derivatives incorporating an oxadiazole moiety. These compounds exhibited favorable interactions with key breast cancer-related proteins, demonstrated enhanced dynamic stability within their binding sites, and adhered to established drug-likeness principles. Importantly, these compounds displayed promising oral absorption (88%) in preliminary assessments and exhibited no significant toxicity. These findings suggest that these novel dihydropteridone-oxadiazole derivatives warrant further investigation as potential multifunctional agents for the treatment of breast cancer cells (MCF-7). |
| format | Article |
| id | doaj-art-10ff0f7c1e9d4c63abe874da28c6b7ce |
| institution | DOAJ |
| issn | 2296-2646 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Chemistry |
| spelling | doaj-art-10ff0f7c1e9d4c63abe874da28c6b7ce2025-08-20T02:45:15ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462025-07-011310.3389/fchem.2025.15905931590593In silico design of novel dihydropteridone derivatives with oxadiazoles as potent inhibitors of MCF-7 breast cancer cellsMourad Aloui0Mohamed El fadili1Mohammed Er-rajy2Somdutt Mujwar3Hatem A. Abuelizz4Sara Er-rahmani5Elhalaoui Menana6LIMAS Laboratory, Faculty of Sciences Dhar El Mahraz, Sidi Mohamed Ben Abdellah University, Fez, MoroccoLIMAS Laboratory, Faculty of Sciences Dhar El Mahraz, Sidi Mohamed Ben Abdellah University, Fez, MoroccoLIMAS Laboratory, Faculty of Sciences Dhar El Mahraz, Sidi Mohamed Ben Abdellah University, Fez, MoroccoChitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, IndiaDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi ArabiaDipartimento di Chimica, Universita’ di Torino, Torino, ItalyLIMAS Laboratory, Faculty of Sciences Dhar El Mahraz, Sidi Mohamed Ben Abdellah University, Fez, MoroccoIntroductionPharmaceutical treatment protocols or combination therapies based on chemical compounds make it possible to target cancer cells, which can be complicated by several factors, including their resistance to bioactive compounds and the potential for drugs to damage certain healthy cells.MethodsThis project was designed to assess the structural relationship between new dihydropteridone-derived compounds bearing an oxadiazole moiety and their corresponding cytotoxicity against breast cancer, using computational chemistry tools. The aim of this research is to better understand how compound properties influence their activity and to understand the underlying mechanisms, which could then be integrated into the anticancer drug design process with a view to recommending new optimized compounds likely to have the desired activity.Results and discussionsThe results show that the predicted molecules possess enhanced selective cytotoxic inhibitory activity against breast cancer cells (MCF-7). Guided by these analyses, we designed five novel dihydropteridone derivatives incorporating an oxadiazole moiety. These compounds exhibited favorable interactions with key breast cancer-related proteins, demonstrated enhanced dynamic stability within their binding sites, and adhered to established drug-likeness principles. Importantly, these compounds displayed promising oral absorption (88%) in preliminary assessments and exhibited no significant toxicity. These findings suggest that these novel dihydropteridone-oxadiazole derivatives warrant further investigation as potential multifunctional agents for the treatment of breast cancer cells (MCF-7).https://www.frontiersin.org/articles/10.3389/fchem.2025.1590593/fullQSARmolecular dockingoxadiazolemolecular dynamicsADMET proprietyMCF-7 |
| spellingShingle | Mourad Aloui Mohamed El fadili Mohammed Er-rajy Somdutt Mujwar Hatem A. Abuelizz Sara Er-rahmani Elhalaoui Menana In silico design of novel dihydropteridone derivatives with oxadiazoles as potent inhibitors of MCF-7 breast cancer cells Frontiers in Chemistry QSAR molecular docking oxadiazole molecular dynamics ADMET propriety MCF-7 |
| title | In silico design of novel dihydropteridone derivatives with oxadiazoles as potent inhibitors of MCF-7 breast cancer cells |
| title_full | In silico design of novel dihydropteridone derivatives with oxadiazoles as potent inhibitors of MCF-7 breast cancer cells |
| title_fullStr | In silico design of novel dihydropteridone derivatives with oxadiazoles as potent inhibitors of MCF-7 breast cancer cells |
| title_full_unstemmed | In silico design of novel dihydropteridone derivatives with oxadiazoles as potent inhibitors of MCF-7 breast cancer cells |
| title_short | In silico design of novel dihydropteridone derivatives with oxadiazoles as potent inhibitors of MCF-7 breast cancer cells |
| title_sort | in silico design of novel dihydropteridone derivatives with oxadiazoles as potent inhibitors of mcf 7 breast cancer cells |
| topic | QSAR molecular docking oxadiazole molecular dynamics ADMET propriety MCF-7 |
| url | https://www.frontiersin.org/articles/10.3389/fchem.2025.1590593/full |
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