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.

Misael Ferreira ¹, Laura Sartori Assunção ², Adny Henrique Silva ³, Fabíola Branco Filippin-Monteiro ⁴, Tânia Beatriz Creczynski-Pasa ², Marcus Mandolesi Sá ⁵

Affiliations

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: marcus.sa@ufsc.br.

PMID: 28222315 DOI: 10.1016/j.ejmech.2017.02.013

Abstract

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.

Keywords

Allylic bromides; Antitumor activity; DNA fragmentation; Isothiouronium salts; Leukemia.

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