Synthesis, Characterization, and Pharmacological Evaluation of Novel Ferrocene-Based Compounds with Anti-Inflammatory and Antihypothyroid Activities

Abstract

The present study evaluated the pharmacological potential of newly synthesized ferrocenebased compounds as anti-thyroid agents using both in vivo and in silico approaches. Experimental hypothyroidism was induced in male Wistar rats using benzylthiouracil (BTU), followed by treatment with three ferrocene derivatives (FMA, FCMphA, and FCMphB) and comparison with levothyroxine as a reference drug. Physiological, biochemical, hormonal, oxidative stress, and histopathological parameters were assessed. In addition, ADMET prediction and molecular docking studies targeting thyroid hormone receptors (T3 and T4) were performed to evaluate pharmacokinetic properties and binding affinity. The results confirmed successful induction of hypothyroidism, as evidenced by increased TSH levels, decreased T3 and T4 concentrations, oxidative stress, and histopathological alterations in thyroid, liver, and kidney tissues. Treatment with ferrocene derivatives, particularly FMA and FCMphB, significantly improved thyroid hormone balance, reduced oxidative stress markers, enhanced antioxidant enzyme activities (GSH, SOD, CAT), and preserved tissue architecture. Moreover, the synthesized compounds exhibited no significant hepatic, renal, or hematological toxicity. In silico analysis revealed favorable drug-likeness and ADMET profiles for the ferrocene derivatives. Molecular docking studies demonstrated strong binding affinities toward thyroid hormone receptors, especially for FMA and FCMphB, with binding energies comparable to or better than levothyroxine. Overall, these findings suggest that ferrocene-based compounds possess promising therapeutic potential as anti-thyroid agents through antioxidant, metabolic, and receptor-mediated mechanisms.