Targeting redox balance: antioxidant effects of thiosemicarbazones on human peripheral blood

Abstract

Introduction. Thiosemicarbazones represent a class of organic compounds with well-documented pharmacological properties, including antitumor, antimicrobial, and antiviral activities. Contemporary research highlights their role in modulating cellular redox equilibrium through antioxidant pathway regulation. The growing interest in copper-based coordination complexes with thiosemicarbazones is driven by the unique redox flexibility and high biocompatibility of copper ions, properties that underlie their potential in therapeutic and diagnostic applications. This investigation assessed the capacity of specific local bioactive thiosemicarbazones to impact the antioxidant system using in vitro methodologies. Material and methods. Peripheral blood samples from ten healthy volunteers were used to evaluate in vitro the influence of 10 copper-based coordination complexes with thiosemicarbazones at concentrations of 10.0 μM/L and 1.0 μM/L on antioxidant markers ‒ total antioxidant activity (via ABTS assay), total antioxidant capacity, antioxidant substance mass, and antioxidants total activity. Results. Data indicated that targeted copper-based coordination complexes with thiosemicarbazones affect general antioxidant markers. The study demonstrates that thiosemicarbazones exhibit concentration- and structure-dependent redox modulation, disclosing distinct mechanisms of action across three structural classes – benzothiazole, phenyl, and allyl thiosemicarbazone derivatives. Structural optimization (e.g., benzothiazole with methoxy groups) yields compounds like MG-22 that maintain redox equilibrium, while pro-oxidant variants (CMA-18) offer therapeutic potential through selective oxidative cytotoxicity. Conclusions. Copper-based coordination complexes with thiosemicarbazones represent a promising class of redox modulators with tunable biological effects. Their bidirectional activity, manifested by stimulation or inhibition of antioxidant mechanisms, confirms the potential of these derivatives as selective therapeutic agents. When these results are integrated in the context of personalized medicine, thiosemicarbazones become valuable candidates in the development of therapeutic strategies aimed at maintaining cellular homeostasis, especially in pathologies characterized by increased oxidative stress, such as cancer and neurodegenerative diseases.