New platinum(iv)-aminoxyl complexes (PACs) 2a,b, bearing an aminoxyl radical with antioxidant properties in the equatorial position and axial dichloroacetate ligands capable of inhibiting the energy production in tumor cells through aerobic glycolysis were synthesized. Complexes 2a,b are characterized by moderate lipophilicity (log Pow ∼2) and differ in the redox properties of aminoxyls. The cytotoxicity of complexes 2a,b was studied on tumor (HeLa, HepG2, MCF-7) and non-cancer cells Vero in comparison with cisplatin (CP), satraplatin (JM216), and previously described PNCs 3a,b bearing axial acetate ligands. The cytotoxicity of 2a,b for tumor cells (IC50 19–171 µmol L−1) is 2–11 times higher than that of complexes 3a,b and comparable to IC50 values for CP and JM216 (10–187 µmol L−1). For non-cancer cells Vero, the cytotoxicity of 2a,b (62–124 µmol L−1) is significantly lower as compared to CP and JM216 (17.6–33 µmol L−1).

We studied the possibility of inhibition of histone deacetylases (HDAC) in the nuclear extract of HeLa cells by N1-hydroxy-N4-(pyridin-4-yl)succinamide (compound 1). Compound 1 inhibits HDAC and showed low toxicity for A-172, HepG2, HeLa, MCF-7, and Vero cells. HeLa cells were most sensitive to the compound. Increasing the interval between administration of compound 1 and the chemotherapeutic agent to 8 h led to an increase in the cytotoxic effect of cisplatin (actinomycin D) on HeLa cells. The combination of compound 1 with cisplatin (actinomycin D) reduced the cytotoxic effect of these drugs for non-tumor Vero cells.

Synthesis, spectral properties, and photodynamic activity of water-soluble amino acid fullerene C-60 derivatives (AFD) and four original AFD-PPa dyads, obtained by covalent addition of dye pyropheophorbide (PPa) to AFD, were studied. In aqueous solution, these AFD-PPa dyads form nanoassociates as a result of self-assembly. In this case, a significant change in the absorption spectra and strong quenching of the dye fluorescence in the structure of the dyads were observed. A comparison of superoxide or singlet oxygen generation efficiency of the studied compounds in an aqueous solution showed the photodynamic mechanism switching from type II (singlet oxygen generation of the native dye) to I type (superoxide generation of dyads). All dyads have pronounced phototoxicity on cells Hela with IC50 9.2 mu M, 9.2 mu M, 12.2 mu M for dyads Val-C-60-PPa, Ala-C-60-PPa and Pro-C-60-PPa, respectively. Such facilitation of type I photodynamic mechanism could be perspective against hypoxic tumors. (C) 2021 Published by Elsevier B.V.

We performed a comparative study of the cytotoxicity of cisplatin, JM216 complex, and aminonitroxyl platinum(IV) complexes for HeLa cells grown in monolayer and 3D culture. The growth dynamics of spheroids was studied and optimal conditions for evaluation of cytotoxicity were determined. Spheroids were less sensitive to the test compounds than cells in a monolayer. The resistance index (RI) of spheroids was determined as the ratio of IC50 for spheroids to IC50 for monolayer culture. Resistance index was 5.0±1.5 for cisplatin and ranged from 1.8 to 2.3 for platinum(IV) complexes. The observed differences are related to different physicochemical properties of the complexes and different mechanisms of their penetration into cells.

The synthesis of water-soluble dyads PFD-Chl(1), PFD-Chl(Zn) and PFD-Chl(2) based on a polyanionic fullerene [60] derivative PFD covalently linked to chlorin e 6 was described. Photophysical properties, generation of superoxide and singlet oxygen in water and liposomes, and photodynamic activity on HeLa cancer cells of obtained dyads were analyzed. The significant influence of linker length between fullerene[60] core and dye, presence of metal (Zn) atom in chlorin moiety on photophysical properties, and photodynamic activity of the dyads was demonstrated. All dyads exhibit quenching of chlorin fluorescence by 7-120 times due to the electron transfer from the dye to fullerene and they formed nanoassociates in aqueous solutions with an effective radius in the range of 30-500 nm due to their pronounced amphiphilic properties. Such nanoassociates were able to effectively interact with membranes of liposomes, which led to a sharp increase of fluorescence signal. This effect could be applied for the design of various fullerene-based nanoscale switch-off systems. The dyad PFD-Chl(1) - with the shortest linker and metal-free dye - had the superoxide generation efficiency 5.6 and 3.4 times higher compared to free chlorin Ce6 in water and liposomes, respectively, while its singlet oxygen generation was reduced. The phototoxicity of this dyad in HeLa cells was almost equal to that of the native chlorin, despite the reduction of singlet oxygen generation efficiency. Upon the incorporation of zinc atom into a chlorin moiety of this dyad, photodynamic activity and phototoxicity of PFD-Chl(Zn) dyad became negligible. The PFD-Chl(2) dyad - with the longest linker and metal-free chlorin - had about two times lower photodynamic activity and phototoxicity compared to Ce6 due to weak interaction between fullerene core and the dye. A significant increase of the type I pathway efficiency, demonstrated in the PFD-Chl(1) dyad, could be applied for the creation of photosensitizers, highly effective against hypoxic tumors. The demonstrated approach opens up vast opportunities for a directional design of highly efficient fullerene-based water-soluble photosensitizers for photodynamic therapy.

The beginning of the Scottish Reformation was connected with a new stage in understanding the essence of human and his moral nature. The experience of the end of time and the extremity of human existence intensified the search for symbolic truths and the struggle for its interpretations. The outbreaks of witchcraft panic in Early Modern Scotland became the consequences of those crucial changes. The ideas about evil magic, witches and their patrons were based on the concept of evil, perceived as a violation of moral prohibitions, rebellion aimed at destruction of preset order, as well as affective behavior and refusal of self-control. In the second half of the 16th century, the Reformation in Scotland returned the devil to the area of actual religious experiences. The article analyzes the devil’s myth in three of its aspects: ethos, gnosis and praxis. The ethical aspect of the devil is evil following from the imperfect human nature and generating a misfortune, as well as personification of all the troubles and injustices of the world. The gnostic aspect of the devil is the source for new forms of knowledge, the mysteries of the universe, opposing God's will and tempting the human pride. Finally, the devil in practical terms is identified with individual vices and affects, as well as with tabooed social practices. The study of experiencing sin and covenanting with the devil is associated with a difficult methodological problem: how much is knowable such private thing as faith? The task of reconstructing deep layers of thinking may be solved by analyzing personal letters and diaries. doi 10.17072/ 2219-3111-2018-2-21-30

We studied the function of the antioxidant system in tumor cell lines MCF-7 and H1299 that differ by the state of tumor suppressor gene p53. Exposure to different classes of cytotoxic compounds induced several types of antioxidant system responses that depend on the type of cell line. The effects of platinum(II) and platinum(IV) complexes on activity of antioxidant enzymes vary, which can be explained by differences in their accumulation and biotransformation in tumor cells. Triazole and oxazolidinone derivatives had little effect on activity of superoxide dismutase and catalase in H1299 cells, but increased superoxide dismutase activity in MCF-7 cells.