2 articles
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.
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.
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.
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.
Identification, study and testing of new remedies for treatment approaches of diseases, resulting from imbalance between oxidants and antioxidants in favor of oxidants, with potentially destructive potential and pathogenesis in liver disorders is of particular interest due to the increase in incidence and severity of these pathologies.
The action of novel local copper coordination compounds, thiosemicarbazide derivatives - CMD-4, CMJ-33 and CMT-67, was evaluated in experiments on white rats after subcutaneous administration in two different doses (0.1 and 1.0 µM / kg) 3 times a week for 30 days. The main indices of oxidative stress were evaluated: the level of malonic dialdehyde (MDA), nitric oxide derivatives (NO), S-nitrosothiols, advanced glycation end products (AGEs), advanced oxidation protein products (AOPP) and ischemia-modified proteins (IMP), and antioxidant system: - superoxidismutase (SOD) and catalase activity (CAT), the level of histidine (His) and total antioxidant activity (TAA) in liver tissue of white rats.
The administration of CC resulted in the reduction of oxidative stress indices - MDA, AGEs and S-nitrosothiols, which denotes the antioxidant effect of the studied compounds. The level of NO and AOPP derivatives does not change substantially. When administering CMD-4 (1 µM / kg), SOD activity and catalase function decreased markedly. Changes in the content of His and TAA have been shown to be inconclusive, maintaining within the limits of the values recorded in the control group.
The elucidation of the modifications of the free radicals processes in liver tissues, which are the basis of the CC action, broadens the theoretical knowledge about the biological properties of a number of chemical compounds; as well provide new possibilities to explore perspective objects in order to obtain new efficient drug preparations.