S-(4-Methoxyphenyl)-4-methoxybenzenesulfonothioate as a Promising Lead Compound for the Development of a Renal...

Area of Science:

• Medicinal Chemistry
• Cancer Biology
• Organic Synthesis

Background:

• Organosulfur compounds exhibit cytotoxic effects on various cancer cell lines.
• Disulfides and thiosulfonates induce apoptosis, endoplasmic reticulum stress, and the unfolded protein response.

Purpose of the Study:

• Synthesize and evaluate novel organosulfur compounds for anti-cancer activity.
• Investigate the mechanism of action, including tubulin polymerization inhibition and cytotoxicity.

Main Methods:

• Synthesis of three p-substituted symmetric diaryl disulfides and three diaryl thiosulfonates.
• Assay of tubulin polymerization inhibition.
• Cytotoxic activity assessment against seven human cancer cell lines and one non-tumor cell line.

Main Results:

• S-(4-methoxyphenyl)-4-methoxybenzenesulfonothioate (compound 6) inhibited tubulin polymerization.
• Compound 6 demonstrated significant antiproliferative effects, particularly against the 786-0 cell line, with high selectivity.
• Compound 6 induced caspase-3 activation and G2/M cell-cycle arrest in 786-0 cells, leading to complete proliferation inhibition and cell death.

Conclusions:

• Compound 6 is a potent anti-cancer agent with a promising selectivity profile.
• The mechanism involves tubulin polymerization inhibition, apoptosis induction, and cell-cycle arrest.
• Organosulfur compounds, particularly diaryl thiosulfonates, represent a valuable class for cancer therapy development.