New Metformin Derivatives as Promising Anticancer Agents: A Computational and Experimental Study

Despite significant therapeutic developments, cancer remains a major cause of global mortality, underscoring the urgent need for novel and effective anticancer agents. This study outlines the rational design, in silico evaluation and synthesis of five novel metformin derivatives. Initially, the preliminary activity of these compounds as anticancer agents was assessed through molecular docking using CCDC GOLD suite software (2025) to indicate how the compounds would interact with the human estrogen receptor alpha (ERα, PDB ID: 3ERT), a key therapeutic target. Pharmacokinetic and drug-likeness properties including molecular weight, Log P, Lipinski's Rule of Five, blood-brain barrier permeability, and key hydrogen-bonding interactions with the receptor were subsequently evaluated to confirm their viability as potential drug candidates. All compounds showed favorable binding affinities for the receptor's active site. Notably, compound [1] exhibited a PLP fitness score (62.807) higher than the reference ligand (Methotrexate) which scored 61.76.Following the reliable computational results, all of the designed molecules [C1-C5] were synthesized successfully and characterized by melting point, FT-IR, 1H NMR and 13C NMR spectroscopy. The pharmacokinetic results showed that all the compounds adhered to Lipinski's Rule, expected to be well-absorbed from the gut with high topological polar descriptors. The present research represents a preliminary evaluation of the anticancer activity and requires further investigations by in vitro and / or in vivo studies.