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

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 r2 = 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.

Exploring Citrus sinensis Phytochemicals as Potential Inhibitors for Breast Cancer Genes BRCA1 and BRCA2 Using Pharmacophore Modeling, Molecular Docking, MD Simulations, and DFT Analysis

“…The production phase was then run for 100 ns. The system pressure was monitored using the Berendsen barostat, and the temperature was kept stable using the Langevin thermostat . We applied the AMBER22 Particle Mesh Ewald (PME) algorithm to calculate long-range electrostatic interaction.…”

“…Values of E HOMO , E LUMO , and E HOMO–LUMO energy gap determine the stability (S), electron affinity (A.F), and ionization potential (I.P) of the isolated phytochemicals, respectively. The molecule is polarized and active if the value of the energy gap (Δ E ), as well as kinetic bioavailability, is low. , …”

“…Additionally, the ratio of phytochemicals for anti-breast cancer compounds was taken as 11:40 when phytochemicals were divided into training and test sets. Forge V6.0 software for the Field Template module was applied for visualization of generated fields . The conformation hunt was selected as accurate but slow, and from the library of 69 compounds, the information about shape and field was analyzed.…”

“…Furthermore, the template represents the bioactive conformation of phytochemicals as well. For the generation of field QSAR, the regression coefficient ( r 2 ), as well as the cross-regression coefficient ( q 2 ), was calculated for each ligand …”

“…All of the parameters of toxicity are given in the table containing 70 compounds. Twenty-six compounds among 70 compounds exhibited no toxicity …”