pharmacophore identification BarberriesDerivatives as Bcl-۲ Inhibitors for Cancer Treatment: MolecularDocking-Based

Background & Objective: The B-cell lymphoma ۲ (Bcl-۲)protein is a crucial regulator of apoptosis, both in healthy andcancerous cells. In cancer cells, Bcl-۲ is often overexpressed,leading to the suppression of apoptosis and allowing cancer cellsto survive and divide uncontrollably. Berberine and canadineare two natural alkaloids found in Barberries that have potentialanti-cancer properties. Berberine has been shown to have antiproliferativeand pro-apoptotic effects on various cancer cells,such as breast, colon, lung, liver, and pancreatic cancer. It mayalso enhance the efficacy of chemotherapy drugs. Canadine, onthe other hand, has cytotoxic effects on cancer cells and couldbe a natural alternative to conventional chemotherapy drugs. Ithas been found to inhibit the growth of cancer stem cells, whichare responsible for cancer recurrence and metastasis.Materials & Methods : In drug discovery, homology modelingof the Bcl-۲ protein was performed using Swiss-Model, and theresulting protein had an overall quality factor of ۹۹.۳% accordingto the Pyre۲ server. We further investigated the interactionbetween the Bcl-۲ protein and berberine/canadine using moleculardocking experiments with PyRx ۰.۸ software.Result: Berberine and canadine showed binding affinity energiesof -۶.۵ and -۶.۶, respectively, to the Bcl-۲ protein. The effectsof Barberries on Bcl-۲ and cancer cells suggest that it haspotential as a therapeutic agent for the treatment of cancer. Furtherstudies are needed to investigate the mechanisms of actionand evaluate the efficacy and safety of these natural compoundsas potential anti-cancer drugs.Conclusion: Berberine and canadine have shown promising results,and they may hold great promise for the development ofnew and effective cancer therapies.

کلیدواژه ها:

cancer cells ، Bcl-۲ ، Barberries derivatives ، pharmacophore ، molecoular docking