Allylic isothiouronium salts: The discovery of a novel class of thiourea analogues with antitumor activity
- Eur J Med Chem. 2017 Mar 31:129:151-158. doi: 10.1016/j.ejmech.2017.02.013.
- 1. Departamento de Química, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-900, Brazil.
- 2. Departamento de Ciências Farmacêuticas, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-900, Brazil.
- 3. Departamento de Bioquímica, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-900, Brazil.
- 4. Departamento de Análises Clínicas, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-900, Brazil.
- 5. Departamento de Química, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-900, Brazil. Electronic address: [email protected].
A series of 28 aryl- and alkyl-substituted isothiouronium salts were readily synthesized in high yields through the reaction of allylic bromides with thiourea, N-monosubstituted thioureas or thiosemicarbazide. The S-allylic isothiouronium salts substituted with aliphatic groups were found to be the most effective against leukemia cells. These compounds combine high antitumor activity and low toxicity toward non-tumoral cells, with selectivity index higher than 20 in some cases. Furthermore, the selected isothiouronium salts induced G2/M cell cycle arrest and cell death, possibly by Apoptosis. Therefore, these compounds can be considered as a promising class of antitumor agents due to the potent cytostatic activity associated with high selectivity.