Healthy lifestyle: Philosophical dimension

Introduction. The article deals with the issue of “healthy lifestyle” as a multidimensional phenomenon that requires complexity in the research process, and also substantiates the need to overcome the limitations of private scientifi c methodology. Philosophical understanding of the problem of health and the phenomenon of a healthy lifestyle is carried out in the modern context of the development of knowledge. Theoretical analysis. To substantiate the integrity, the intellectual potential of the philosophical tradition is involved, a critical analysis of the one-dimensionality of natural-scientifi c ideas about the corporeality of a person is carried out. The multifunctionality of a healthy lifestyle and its integration into the cultural and mental basis of modern civilization are analyzed. The potential of the ideas of idealism, realism, pragmatism and existentialism for the study of the problem of education and human development is revealed. The valeological component of life and health of the population of the country is indicated. The author’s vision of the phenomenon of a healthy lifestyle, as one of the phenomena of social life, is proposed. The role of education in the formation of a healthy lifestyle of the younger generation is determined. The consequences of the application of body-oriented practices as a new direction of culture are shown. Conclusion. It is generalized that a healthy lifestyle is a safe state of human existence. The necessity of creating a philosophy of a healthy lifestyle is substantiated

New Hybrid Compounds Combining Fragments of Usnic Acid and Thioether Are Inhibitors of Human Enzymes TDP1, TDP2 and PARP1

Tyrosyl-DNA phosphodiesterase 1 (TDP1) catalyzes the cleavage of the phosphodiester bond between the tyrosine residue of topoisomerase 1 (TOP1) and the 3′ phosphate of DNA in the single-strand break generated by TOP1. TDP1 promotes the cleavage of the stable DNA–TOP1 complexes with the TOP1 inhibitor topotecan, which is a clinically used anticancer drug. This article reports the synthesis and study of usnic acid thioether and sulfoxide derivatives that efficiently suppress TDP1 activity, with IC50 values in the 1.4–25.2 μM range. The structure of the heterocyclic substituent introduced into the dibenzofuran core affects the TDP1 inhibitory efficiency of the compounds. A five-membered heterocyclic fragment was shown to be most pharmacophoric among the others. Sulfoxide derivatives were less cytotoxic than their thioester analogs. We observed an uncompetitive type of inhibition for the four most effective inhibitors of TDP1. The anticancer effect of TOP1 inhibitors can be enhanced by the simultaneous inhibition of PARP1, TDP1, and TDP2. Some of the compounds inhibited not only TDP1 but also TDP2 and/or PARP1, but at significantly higher concentration ranges than TDP1. Leader compound 10a showed promising synergy on HeLa cells in conjunction with the TOP1 inhibitor topotecan