The combination of multi-approach studies to explore the potential therapeutic mechanisms of imidazole derivatives as an MCF-7 inhibitor in therapeutic strategies

Maryam Rashid; Ayesha Maqbool; Nusrat Shafiq; Yousef A Bin Jardan; Shagufta Parveen; Mohammed Bourhia; Hiba-Allah Nafidi; Rashid Ahmed Khan

doi:10.3389/fchem.2023.1197665

The combination of multi-approach studies to explore the potential therapeutic mechanisms of imidazole derivatives as an MCF-7 inhibitor in therapeutic strategies

Front Chem. 2023 Jun 27:11:1197665. doi: 10.3389/fchem.2023.1197665. eCollection 2023.

Authors

Maryam Rashid¹, Ayesha Maqbool¹, Nusrat Shafiq¹, Yousef A Bin Jardan², Shagufta Parveen^{1

3}, Mohammed Bourhia⁴, Hiba-Allah Nafidi⁵, Rashid Ahmed Khan⁶

Affiliations

¹ Synthetic and Natural Product Drug Discovery Laboratory, Department of Chemistry, Government College Women University Faisalabad, Faisalabad, Pakistan.
² Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
³ Department of Applied Chemistry, Beijing Institute of Technology, Beijing, China.
⁴ Department of Chemistry and Biochemistry, Faculty of Medicine and Pharmacy, Ibn Zohr University, Laayoune, Morocco.
⁵ Department of Food Science, Faculty of Agricultural and Food Sciences, Laval University, Quebec City, QC, Canada.
⁶ Nuclear Institute for Agriculture and Biology (NIAB), Faisalabad, Pakistan.

Abstract

Breast cancer covers a large area of research because of its prevalence and high frequency all over the world. This study is based on drug discovery against breast cancer from a series of imidazole derivatives. A 3D-QSAR and activity atlas model was developed by exploring the dataset computationally, using the machine learning process of Flare. The dataset of compounds was divided into active and inactive compounds according to their biological and structural similarity with the reference drug. The obtained PLS regression model provided an acceptable r ² = 0.81 and q² = 0.51. Protein-ligand interactions of active molecules were shown by molecular docking against six potential targets, namely, TTK, HER2, GR, NUDT5, MTHFS, and NQO2. Then, toxicity risk parameters were evaluated for hit compounds. Finally, after all these screening processes, compound C10 was recognized as the best-hit compound. This study identified a new inhibitor C10 against cancer and provided evidence-based knowledge to discover more analogs.

Keywords: MCF-7; breast cancer; drug discovery; imidazole; virtual screening.