S‐(4‐Methoxyphenyl)‐4‐methoxybenzenesulfonothioate as a Promising Lead Compound for the Development of a Renal Carcinoma Agent

Abstract

Organosulfur compounds show cytotoxic potential towards many tumor cell lines. Disulfides and thiosulfonates act through apoptotic processes, inducing proteins associated with apoptosis, endoplasmic reticulum stress, and the unfolded protein response. Three p‐substituted symmetric diaryl disulfides and three diaryl thiosulfonates were synthesized and analyzed for inhibition of tubulin polymerization and for human cancer cell cytotoxic activity against seven tumor cell lines and a non‐tumor cell line. S‐(4‐methoxyphenyl)‐4‐methoxybenzenesulfonothioate (6) exhibited inhibition of tubulin polymerization and showed the best antiproliferative potential, especially against the 786‐0 cell line, being six times more selective as compared with the non‐tumor cell line. In addition, compound 6 was able to activate caspase‐3 after 24 and 48 h treatments of the 786‐0 cell line and induced cell‐cycle arrest in the G2/M stage at the highest concentration evaluated at 24 and 48 h. Compound 6 was able to cause complete inhibition of proliferation, inducing the death of 786‐0 cells, by increasing the number of cells at G2/M and greater activation of caspase‐3.

Switchable Synthesis of Sulfoxides, Sulfones and Thiosulfonates through Selectfluor-Promoted Oxidation with H2O as O-Source

“…Interestingly, when the reactions were conducted with thiophenol 4a and 1.5 equivalents of Selectfluor, thiosulfonate 5a was produced in almost quantitative yield in 5 minutes (Table 3; 5a, 99%). Thiosulfonates exhibited the unique therapeutic properties (e.g., antitumor activity, 23 antitubulin activity 24 ), but the mild and highly efficient synthetic methods, especially using thiophenols/thiols as raw material, remain to be developed. 25 For this reason, different reaction parameters, such as solvents and the dosage of H 2 O and Selectfluor, were further screened (see Supporting Information, Table S1).…”