We discussed and summarized the latest data from the global literature on the action of polyphenolic antioxidants and their metal complexes. The review also includes a summary of the outcomes of theoretical computations and our many years of experimental experience. We employed various methods, including spectroscopy (FT-IR, FT-Raman, NMR, UV/Vis), X-ray diffraction, thermal analysis, quantum calculations, and biological assays (DPPH, ABTS, FRAP, cytotoxicity, and genotoxicity tests). According to our research, the number and position of hydroxyl groups in aromatic rings, as well as the delocalization of electron charge and conjugated double bonds, have a major impact on the antioxidant effectiveness of the studied compounds. Another important factor is metal complexation, whereby high ionic potential metals (e.g., Fe(III), Cr(III), Cu(II)) enhance antioxidant properties by stabilizing electron charge, while the low ionic potential metals (e.g., Ag(I), Hg(II), Pb(II)) reduce efficacy by disrupting electron distribution. However, we observed no simple correlation between ionic potential and antioxidant capacity. This paper gives insights that will aid in identifying new, effective antioxidants, which are vital for nutrition and the prevention of neurodegenerative illnesses. Our results outline the connections between biological activity and molecular structure, offering a foundation for the methodical design of antioxidants. Our review also shows in detail how we use various complementary methods to assess the impact of metals on the electronic systems of ligands. This approach moves beyond the traditional “trial and error” method, allowing for the more efficient and rational development of future antioxidants.

Since the beginning of the human immunodeficiency virus (HIV) epidemic, many groups of drugs characterized by diverse mechanisms of action have been developed, which can suppress HIV viremia. 3-O-(3′,3′-Dimethylsuccinyl) betulinic acid, known as bevirimat (BVM), was the first compound in the class of HIV maturation inhibitors. In the present work, phosphate and phosphonate derivatives of 3-carboxyacylbetulinic acid were synthesized and evaluated for anti-HIV-1 activity. In vitro studies showed that 30-diethylphosphonate analog of BVM (compound 14a) has comparable effects to BVM (half maximal inhibitory concentrations (IC₅₀) equal to 0.02 μM and 0.03 μM, respectively) and is also more selective (selectivity indices: 3450 and 967, respectively). To investigate the possible mechanism of antiviral effect of 14a, molecular docking was carried out on the C-terminal domain (CTD) of HIV-1 capsid (CA)–spacer peptide 1 (SP1) fragment of Gag protein, designated as CTD-SP1, which was described as a molecular target for maturation inhibitors. Compared with interactions between BVM and the protein, an increased number of strong interactions between ligand 14a and protein, generated by the phosphonate group, was observed.

Isothiocyanates (R-NCS) are sulphur-containing phytochemicals. The main source are plants of the Brassicaceae family. The best known plant-derived isothiocyanate is sulforaphane that has exhibited anticancer activity in both in vivo and in vitro studies. Recent attempts to expand their use in cancer therapy involve combining them with standard chemotherapeutics in order to increase their therapeutic efficacy. The aim of this paper is to determine the impact of sulforaphane and its natural analog alyssin on the anticancer activity of the well-known anticancer drug 5-fluorouracil. The type of drug-drug interactions was determined in prostate and colon cancer cell lines. Confocal microscopy, western blot and flow cytometry methods were employed to determine the mechanism of cytotoxic and cytostatic action of the combinations. The study revealed that additive or synergistic interactions were observed between 5-fluorouracil and both isothiocyanates, which enhanced the anticancer activity of 5-fluorouracil, particularly in colon cancer cell lines. An increased cytostatic effect was observed in case of alyssin while for sulforaphane the synergistic interaction with 5-fluorouracil involved an intensification of apoptotic cell death.

Lupane-type pentacyclic triterpenes such as betulin and betulinic acid play an important role in the search for new therapies that would be effective in controlling viral infections. The aim of this study was the synthesis and evaluation of in vitro anti-HIV-1 activity for phosphate derivatives of 3-carboxyacylbetulin 3–5 as well as an in silico study of new compounds as potential ligands of the C-terminal domain of the HIV-1 capsid–spacer peptide 1 (CA-CTD-SP1) as a molecular target of HIV-1 maturation inhibitors. In vitro studies showed that 28-diethoxyphosphoryl-3-O-(3′,3′-dimethylsuccinyl)betulin (compound 3), the phosphate analog of bevirimat (betulinic acid derivative, HIV-1 maturation inhibitor), has IC₅₀ (half maximal inhibitory concentration) equal to 0.02 μM. Compound 3 inhibits viral replication at a level comparable to bevirimat and is also more selective (selectivity indices = 1250 and 967, respectively). Molecular docking was used to examine the probable interaction between the phosphate derivatives of 3-carboxyacylbetulin and C-terminal domain (CTD) of the HIV-1 capsid (CA)–spacer peptide 1 (SP1) fragment of Gag protein, designated as CTD-SP1. Compared with interactions between bevirimat (BVM) and the protein, an increased number of strong interactions between ligand 3 and the protein, generated by the phosphate group, were observed. These compounds might have the potential to also inhibit SARS-CoV2 proteins, in as far as the intrinsically imprecise docking scores suggest.