Design of a New Inhibitory Ligand for Bcl-۲-Induced Apoptosis to Enhance Breast Cancer Treatment Using Bioinformatics Tools

Breast cancer (BC) is the most commonly diagnosed cancer among women globally. A mix of environmental and genetic factors significantly contributes to the development of this disease. Inhibiting the Bcl-۲ protein enhances cancer treatment by promoting apoptosis, making cancer cells more susceptible to cell death and helping to overcome drug resistance. This inhibition can also lead to cell cycle arrest, reducing tumor growth, and enhancing the immune response against cancer cells. Bcl-۲ inhibitors are often combined with other therapies, amplifying their effectiveness. Overall, targeting Bcl-۲ represents a promising strategy, especially for resistant cancer types. Recent research suggests that Thymoquinone, and Carvacrol , derived from Nigella_sativa demonstrated anti-cancer and anti-inflammatory effects. These findings suggested that the new ligand compared to two antihypertensive ligands Thymoquinone, and Carvacrol may be an appropriate option for preventing and treating breast cancer. Methods: This research project used PubChem and PDB to analyze the structure of Bcl۲ / ۱G۵M. In addition, the new ligand designed by ChemDrow and Chem۳D. Molecular docking was screened using iGEMDOCK version ۲.۱ with docking accuracy settings (GA parameters): population size۳۰۰, generations۷۰, and the number of solutions۳. The calculated ligand receptor (protein) interaction energy is represented by docking scores (DOS). More negative scores indicate a stronger likelihood of binding. Results: The binding of Bcl۲ / ۱G۵M protein to two selected ligands was investigated. The energy levels of both ligands Thymoquinone (-۶۸.۸۶) and Carvacrol (-۶۱.۴۷) exhibit a low magnitude. However, leveraging the characteristics of these two ligands, a sophisticated ligand was designed, leading to the discovery of the ۶-isopropyl-۳-methylcyclohexane-۱,۲,۴-triol ligand with enhanced energy yield (-۷۷.۶) and superior outcomes. Hence, the discernment of the most efficacious ligand for the ۱G۵M protein was achieved when compared to Thymoquinone and Carvacrol. Ligand properties: Chemical Formula: C۱۰H۲۰O۳, Exact Mass: ۱۸۸/۱۴۱, Molecular Weight: ۱۸۸/۲۶۷ Conclusion: The findings revealed that novel ligand which designed for the study can be a potent inhibitor of breast cancer. Among them, the protein Bcl۲ (۱G۵M) derivative may be the more effective for the treatment of the disease. Based on the findings. It is recommended that in-vitro and in-vivo studies be carried out to determine the efficacy of this ligand against breast cancer disease.

کلیدواژه ها:

Thymoquinone ، Carvacrol ، Drug-design ، Bcl-۲-Induced apoptosis ، Breast cancer