Design, synthesis and biological effects studies of new imidazole-oxadiazole derivative compounds
JOURNAL OF MOLECULAR STRUCTURE, vol.1379, 2027 (SCI-Expanded, Scopus)
- Publication Type: Article / Article
- Volume: 1379
- Publication Date: 2027
- Doi Number: 10.1016/j.molstruc.2026.146999
- Journal Name: JOURNAL OF MOLECULAR STRUCTURE
- Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core, Chimica, Compendex, INSPEC, Academic Search Ultimate (EBSCO), Engineering Source (EBSCO)
- Anadolu University Affiliated: Yes
Abstract
Breast cancer is one of the most common types of cancer in women, and inhibition of the aromatase enzyme, which plays a key role in estrogen synthesis, constitutes an important therapeutic approach, particularly in the treatment of hormone-dependent breast cancer. Azoles are five-membered aromatic heterocycles containing one nitrogen atom of their ring systems. In recent years, molecules bearing the azole ring have emerged, particularly as aromatase inhibitors. Molecular docking studies have shown that the azole ring interacts with the iron at the center of the heme moiety in the active site of aromatase. Novel hybrid derivatives containing the imidazole ring, known for its aromatase inhibitory activity, and the aryl acyl structure, known for its MAO (Monoamine oxidase) inhibitory activity, were designed. Within the scope of this project, 11 new imidazole-oxadiazole derivative compounds were synthesized, and their structures were elucidated using 1HNMR, 13CNMR, and HRMS spectroscopic techniques. The apoptotic potential of the derivatives found to be effective against the MCF-7 cell line was assessed by flow cytometry. The inhibitory potencies of the active derivatives on aromatase and MAO enzymes were determined by in vitro methods. Among the synthesized compounds, 3d and 3h demonstrated notable antiproliferative activity against the MCF-7 breast cancer cell line (IC50 = 8.55 & micro;M and 13.69 & micro;M, respectively). Enzyme inhibition studies revealed that compound 3d exhibited strong dual inhibitory activity against aromatase (IC50 = 0.064 & micro;M) and MAO-A (IC50 = 0.090 & micro;M). Evaluation of molecular docking and dynamic studies reveals that electron-withdrawing groups in the phenyl ring, particularly the chlorine atoms (3d, 3h, and 3i), play a decisive role in both aromatase and MAO inhibitory activity. The dichloro substitution model enhances the stability of the ligand-enzyme complex by forming significant halogen bond interactions with the Met374 residue in the aromatase active site.