This study reports the systematic evaluation of ferrocenylmethylcyanophenyl (FcCN) and ferrocenylmethylcyanophenylacetamide (FcCNCO) derivatives as dual anti-inflammatory and antidiabetic agents. The FcCN derivatives were synthesized via nucleophilic substitution of aminobenzonitrile on methylenic carbons adjacent to quaternary ammonium centers, followed by acylation with acetic anhydride to yield the corresponding FcCNCO derivatives. These well-established reactions constitute a reliable and reproducible synthetic framework for the preparation of the target compounds. In vitro assays demonstrated that Fc2CNCO exhibited superior anti-inflammatory activity (IC50 = 4.17 µM) compared to diclofenac (IC50= 6.40 µM), while Fc4CNCO strongly inhibited α-amylase (IC50 = 1.15 µM), approaching the potency of acarbose (IC50= 0.33 µM). Molecular docking and 100 ns molecular dynamics simulations confirmed stable protein–ligand interactions, consistent with the experimental results, and highlighted the key roles of hydrogen bonding, hydrophobic contacts, and π–stacking in driving selectivity. Structure–activity relationship analysis revealed substitution-dependent trends: ortho-acetamide substitution enhanced anti-inflammatory potency, whereas para-substitution favored α-amylase inhibition. These findings establish ferrocenyl scaffolds as promising multifunctional drug leads and provide rational design principles for future agents targeting comorbid inflammatory and metabolic disorders.
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