Synthesis, in silico study and cytotoxic evaluation of new benzimidazole derivatives as potential aromatase inhibitors.

IF 3.3 4区医学 Q3 CHEMISTRY, MEDICINAL

Future medicinal chemistry Pub Date : 2026-10-16 DOI:10.1080/17568919.2026.2748643

Ayşen Işık, Nour El-Huda Daoud, Kezban Uçar Çiftçi, Gulsah Congur, Ebru Nur Ay, Emine Rana Bagcı, Şennur Görgülü, Ulviye Acar Çevik, Yusuf Tutar, Yusuf Özkay, Zafer Asım Kaplancıklı

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引用次数: 0

Abstract

Aims: A new series of benzimidazole derivatives (4a-4p) was designed, synthesized, and evaluated as potential aromatase inhibitors with anticancer activity.

Materials and methods: The anticancer effects of the compounds were evaluated using the MCF-7 cell line. Derivatives that showed activity were subjected to an aromatase inhibition assay. Molecular docking, molecular dynamics simulations, and in silico ADMET profiling were performed for the selected compounds.

Results: Among the series, para-substituted derivatives 4d (Cl), 4h (OC₂H₅), and 4k (F) exhibited potent antiproliferative activity with low‑micromolar IC₅₀ values (2.40-2.64 µM), surpassing cisplatin, while maintaining favorable selectivity profiles.

Conclusions: This experimental and computational study identifies 4d as a promising lead for further development as a non-steroidal aromatase inhibitor for breast cancer therapy.

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新型苯并咪唑类芳香酶抑制剂的合成、硅研究及细胞毒性评价。

目的：设计、合成了一系列新的苯并咪唑衍生物（4a-4p），并对其作为潜在的具有抗癌活性的芳香酶抑制剂进行了评价。材料与方法：采用MCF-7细胞株对化合物的抗癌作用进行评价。对显示活性的衍生物进行芳香酶抑制试验。对所选化合物进行了分子对接、分子动力学模拟和ADMET分析。结果：在该系列中，对取代衍生物4d (Cl), 4h （OC2H5）和4k (F)具有较低的微摩尔IC50值（2.40-2.64µM），具有较强的抗增殖活性，超过顺铂，同时保持良好的选择性。结论：这项实验和计算研究确定了4d作为乳腺癌治疗的非甾体芳香化酶抑制剂的进一步发展前景。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Future medicinal chemistry CHEMISTRY, MEDICINAL-

CiteScore

5.80

自引率

2.40%

发文量

118

审稿时长

4-8 weeks

期刊介绍： Future Medicinal Chemistry offers a forum for the rapid publication of original research and critical reviews of the latest milestones in the field. Strong emphasis is placed on ensuring that the journal stimulates awareness of issues that are anticipated to play an increasingly central role in influencing the future direction of pharmaceutical chemistry. Where relevant, contributions are also actively encouraged on areas as diverse as biotechnology, enzymology, green chemistry, genomics, immunology, materials science, neglected diseases and orphan drugs, pharmacogenomics, proteomics and toxicology.