Aloui Mourad, El Fadili Mohamed, Er-Rajy Mohammed, Mujwar Somdutt, Abuelizz Hatem A, Er-Rahmani Sara, Menana Elhalaoui
LIMAS Laboratory, Faculty of Sciences Dhar El Mahraz, Sidi Mohamed Ben Abdellah University, Fez, Morocco.
Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India.
Front Chem. 2025 Jul 28;13:1590593. doi: 10.3389/fchem.2025.1590593. eCollection 2025.
Pharmaceutical 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.
This 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.
The 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).
基于化合物的药物治疗方案或联合疗法能够靶向癌细胞，但这可能会受到多种因素的影响，包括癌细胞对生物活性化合物的耐药性以及药物对某些健康细胞的潜在损害。
本项目旨在利用计算化学工具评估带有恶二唑部分的新型二氢蝶啶酮衍生化合物与其对乳腺癌的相应细胞毒性之间的结构关系。本研究的目的是更好地理解化合物性质如何影响其活性，并了解潜在机制，进而将这些机制整合到抗癌药物设计过程中，以期推荐可能具有所需活性的新型优化化合物。
结果表明，预测的分子对乳腺癌细胞（MCF-7）具有增强的选择性细胞毒性抑制活性。在这些分析的指导下，我们设计了五种含有恶二唑部分的新型二氢蝶啶酮衍生物。这些化合物与关键的乳腺癌相关蛋白表现出良好的相互作用，在其结合位点内显示出增强的动态稳定性，并符合既定的类药原则。重要的是，这些化合物在初步评估中显示出有前景的口服吸收（88%），且无明显毒性。这些发现表明，这些新型二氢蝶啶酮-恶二唑衍生物作为治疗乳腺癌细胞（MCF-7）的潜在多功能药物值得进一步研究。
