Uzmez Zeynep Livanur, Osmaniye Derya, Ozkay Yusuf, Kaplancıklı Zafer Asım
Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey.
Med Chem. 2025;21(4):309-318. doi: 10.2174/0115734064316112240722092935.
Breast cancer is the most common type of cancer among women. Steroidal or non-steroidal aromatase inhibitors (NSAIs) are used clinically, and in most cancer diseases, resistance is the most important problem.
The nitrogenous heterocyclic ring is noteworthy in the structure of non-steroidal aromatase inhibitors. This is the pharmacophore structure for aromatase inhibition. Because the enzyme interacts with the Fe cation of the HEM structure in its active site, the most used agents in the clinic, such as anastrozole and letrozole, contain triazoles in their structures. Within the scope of this study, hybrid compounds containing both imidazole and triazole were synthesized.
The synthesis was carried out by a 4-step reaction. The anticancer effects of the compounds were evaluated by MTT assay performed on A549 and MCF-7 cancer cells. Compound 4d showed anticancer activity against the MCF-7 cell line with IC=6.7342 uM value. This compound exhibited anticancer activity against the A549 cell line with an IC = 17.1761 μM. In the MTT test performed on a healthy cell line to determine the cytotoxic effects of the compounds, the compound showed activity with a value of 4d IC=13.2088 uM. This indicates that the compound is not cytotoxic. Additionally, BrdU analysis was performed to evaluate whether the compound inhibits DNA synthesis. These selective effects of the compounds on breast cancer strengthened their aromatase enzyme inhibitor potential. For this reason, experiments conducted with both and methods revealed a compound with high aromatase inhibitor potential.
The interactions observed as a result of molecular docking and dynamics studies are in harmony with activity studies. In particular, interactions with HEM600 demonstrate the activity potential of the compound.
乳腺癌是女性中最常见的癌症类型。甾体或非甾体芳香酶抑制剂（NSAIs）在临床上被使用，并且在大多数癌症疾病中，耐药性是最重要的问题。
含氮杂环在非甾体芳香酶抑制剂的结构中值得关注。这是芳香酶抑制的药效团结构。由于该酶在其活性位点与HEM结构的铁阳离子相互作用，临床上最常用的药物，如阿那曲唑和来曲唑，在其结构中含有三唑。在本研究范围内，合成了同时含有咪唑和三唑的杂化化合物。
通过4步反应进行合成。通过对A549和MCF - 7癌细胞进行MTT测定来评估化合物的抗癌效果。化合物4d对MCF - 7细胞系显示出抗癌活性，IC值为6.7342 μM。该化合物对A549细胞系表现出抗癌活性，IC = 17.1761 μM。在对健康细胞系进行MTT试验以确定化合物的细胞毒性作用时，化合物4d显示出活性，IC值为13.2088 μM。这表明该化合物没有细胞毒性。此外，进行了BrdU分析以评估该化合物是否抑制DNA合成。这些化合物对乳腺癌的选择性作用增强了它们作为芳香酶抑制剂的潜力。因此，用这两种方法进行的实验揭示了一种具有高芳香酶抑制潜力的化合物。
分子对接和动力学研究结果所观察到的相互作用与活性研究结果一致。特别是与HEM600的相互作用证明了该化合物的活性潜力。
