Sulfur-containing phenolic antioxidants increasing antitumor efficiency of cyclophosphamide and its combination with nitric oxide donor

Abstract

Due to the multifactorial nature of cancer diseases, investigations of combinations of the known cytostatics with substances that are chemosensitizers and act on various molecular target in the organism gain increasing significance. Polyfunctional compounds, whose molecules contain several reaction centers, serve as resources improving the efficiency of the chemosensitizing effect of various substances for chemotherapy by cytostatic agents. Classical representatives of such polyfunctional substances are sulfur-containing derivatives of alkylated phenols, the high oxidation activity of which is determined by a combination of the antiradical activity of the phenol fragments with the antiperoxide activity of the sulfur-containing groups. It is shown that the sulfur-containing phenolic antioxidant sodium S-[3-(3-tert-butyl-4-hydroxyphenyl) propyl] thiosulfate (TC-13) has no antitumor activity but enhances chemotherapeutic activity of cytostatic cyclophosphamide taken in a subtherapeutic dose, increasing the index of average life span of mice with leukemia P388 from 196 to 283%. In addition, a combination of TC-13 with the nitric oxide donor (NaNO₂) increases the antitumor activity of cytostatic cyclophosphamide by 110% for the same experimental model of mice at 50% survived animals.