Experimental and theoretical assessment of salvianolic acid B, ellagic acid, and phorbol esters as drug candidates against breast and prostate cancer

Global efforts to develop innovative anti-cancer lead compounds from natural compounds found in plants have gained advanced momentum, focusing on achieving Sustainable Development Goal (SDG) number 3 on good health and well-being. This investigation identifies ellagic acid and salvianolic acid B as promising natural inhibitors of mTOR, DNA lyase, and topoisomerase II alpha, critical cancer-related enzymes. Salvianolic acid showed stable and stronger binding on its targets with potent growth inhibition across breast (IC50: 14–20 µM) and prostate (IC50: 12–18 µM) cancer cell lines. Also, salvianolic acid displayed consistent root mean square deviation (RMSD) values over 200 ns simulation time. Phorbol esters showed inactivity on cancer cell lines, while ellagic acid showed moderate efficacy and thermodynamic stability. Polyphenols like salvianolic acid have strong target engagement but suffer from poor bioavailability and predicted permeability. This underscores the need for chemical formulation strategies. The toxicity profiles of the studied bioactive compounds were non-hepatotoxic, non-mutagenic, and safe at the cellular level. Compared to the clinically approved drugs (doxorubicin/docetaxel), salvianolic acid B approached benchmark potency, supporting its promising potential as an anticancer agent. Notably, the in silico and in vitro studies validate previous evidence of polyphenols in cancer therapy and introduce salvianolic acid B as a promising lead for poly-targeted anti-cancer drug development. Eventually, for accurate clinical trials, animal experiments and in vivo studies are necessary to confirm the potential preventive and therapeutic effects of these bioactive compounds.