Fe(III)-Salicylhydroxamic acid complex as a potential therapeutic agent: Synthesis, Kinetic evaluation, and molecular targeting in hepatocellular carcinoma

Hepatocellular carcinoma (HCC), a leading cause of cancer-related mortality worldwide, driven by complex molecular alterations, including dysregulation of iron metabolism, oxidative stress, and redox imbalance, which promote tumor progression via iron-dependent oncogenic pathways. The conventional therapies for HCC face limitations including drug resistance and systemic toxicity, necessitating the development of novel multi-targeted therapeutic agents. In this context, the Fe (III)-salicylhydroxamic acid (Fe (III)-SHA) complex, synthesized through a simple aqueous-ethanol procedure, emerges as a promising redox-active compound with potential anticancer activity. This study investigates the redox kinetics of Fe (III)-SHA upon reduction by ascorbic acid and evaluates its therapeutic potential against key HCC-associated proteins: EGFR, BRAF, VEGFR3, and UFO, using computational drug discovery approaches. Kinetic profiling revealed a pH-dependent second-order reaction with a maximum rate constant (k₂) of 16.26 M⁻¹s⁻¹ at pH 5.0, indicating efficient redox reactivity under physiologically relevant conditions. Molecular docking studies demonstrated strong binding affinities, particularly with VEGFR3 (-7.6 kcal/mol), and stable interactions involving hydrogen bonding, hydrophobic forces, and metal coordination. Pharmacokinetic preclinical analysis confirmed favorable drug-like properties, including high solubility, gastrointestinal absorption, and a bioavailability score of 0.55. Collectively, these findings support the dual role of Fe (III)-SHA in modulating redox balance and targeting multiple oncogenic proteins, positioning it as a potential multi-target anticancer “ drug candidate ” for HCC treatment. While the current results are limited to redox kinetics and computational analyses, this work provides a strong rationale for further biological investigation and future in vitro and in vivo validation of Fe (III)-SHA as a drug candidate for HCC therapy.