S-(4-Methoxyphenyl)-4-methoxybenzenesulfonothioate as a Promising Lead Compound for the Development of a Renal Carcinoma Agent |
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| Authors: | Camilla I. Nantes Ingrid D. Pereira Ruoli Bai Dr. Ernest Hamel James C. Burnett Rodrigo J. de Oliveira Prof. Maria de F. C. Matos Prof. Adilson Beatriz Murilo K. A. Yonekawa Prof. Renata T. Perdomo Prof. Dênis P. de Lima Prof. Danielle Bogo Prof. Edson dos A. dos Santos |
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| Affiliation: | 1. Laboratório de Biologia Molecular e Culturas Celulares Faculdade de Ciências Farmacêuticas, Alimentos e Nutrição, Universidade Federal de Mato Grosso do Sul, Av. Costa e Silva s/n, Cidade Universitária, CEP 79070–900 Campo Grande – MS, Brazil;2. Laboratório de Pesquisa 4 - Instituto de Química, Universidade Federal de Mato Grosso do Sul, Av. Senador Müller, 1555, CEP 79070–900 Campo Grande – MS, Brazil;3. Screening Technologies Branch, Developmental Therapeutics Program Division of Cancer Treatment and Diagnosis, Frederick National Laboratory National Cancer Institute (NCI), Frederick, MD 21702 USA;4. Computational Drug Development Group, Screening Technologies Branch Developmental Therapeutics Program Division of Cancer Treatment and Diagnosis Frederick National Laboratory, National Cancer Institute (NCI), Frederick, MD 21702 USA;5. Centro de Estudos e Células Tronco Terapia Celular e Genética Toxicológica, Universidade Federal de Mato Grosso do Sul, CeTroGen NHU, Campo Grande – MS, Brazil;6. Laboratório de Bioquímica Geral e de Microrganismos Instituto de Biociências, Universidade Federal de Mato Grosso do Sul Av. Costa e Silva s/n, Cidade Universitária, CEP 79070–900 Campo Grande – MS, Brazil |
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| 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. |
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| Keywords: | Disulfides thiosulfonates tubulin 786-0 cells caspase-3 |
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