Synthesis, Antioxidant, and Antidiabetic Potential of Ferrocenylmethylnucleobase Compounds: In Vitro, In Silico Molecular Docking, DFT Calculation, and Molecular Dynamic Simulations

ABSTRACT This study presents the synthesis and characterization of a novel series of ferrocenylmethylnucleobase compounds, namely, FcMeAd, FcMeCy, FcMeTh, and (FcMe)₂Ad with promising antioxidant and antidiabetic properties. Spectroscopic techniques confirmed their sandwich‐like geometry, with the nucleobase moiety coordinated to the ferrocene unit. Density functional theory (DFT) optimization revealed alignment with existing crystallographic data and indicated low frontier molecular orbital (FMO) energy gaps, suggesting facile intramolecular charge transfer and potential biological activity. The antidiabetic activity was evaluated in vitro through inhibition assays targeting α‐glucosidase and α‐amylase enzymes, which was supported by in silico molecular docking studies. Among the compounds, FcMeTh exhibited the highest antidiabetic and antioxidant properties due to the presence of carbonyl and amide functionalities, along with an electron‐donating methyl group. Molecular dynamics (MD) simulations confirmed high binding affinity and structural stability of the docked compounds, with strong interactions with the target enzymes, further validating the potential of these compounds as effective inhibitors. Pharmacokinetic and ADMET evaluations indicated their nontoxic, noncarcinogenic nature and suitability for oral administration. The combined in vitro and in silico findings, including the critical insights from MD simulations, suggest that these ferrocenylmethylnucleobase compounds, especially FcMeTh, possess enhanced antioxidant and antidiabetic properties. This highlights their potential as promising therapeutic agents for managing oxidative stress and Type 2 diabetes.