title: Allylic isothiouronium salts: The discovery of a novel class of thiourea analogues with antitumor activity.
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.
authors.affiliation: Departamento de Química, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-900, Brazil.
authors.forename: Misael
authors.initials: M
authors.lastname: Ferreira
authors.affiliation: Departamento de Ciências Farmacêuticas, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-900, Brazil.
authors.forename: Laura Sartori
authors.initials: LS
authors.lastname: Assunção
authors.affiliation: Departamento de Bioquímica, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-900, Brazil.
authors.forename: Adny Henrique
authors.initials: AH
authors.lastname: Silva
authors.affiliation: Departamento de Análises Clínicas, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-900, Brazil.
authors.forename: Fabíola Branco
authors.initials: FB
authors.lastname: Filippin-Monteiro
authors.affiliation: Departamento de Ciências Farmacêuticas, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-900, Brazil.
authors.forename: Tânia Beatriz
authors.initials: TB
authors.lastname: Creczynski-Pasa
authors.affiliation: Departamento de Química, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-900, Brazil. Electronic address: marcus.sa@ufsc.br.
authors.forename: Marcus Mandolesi
authors.initials: MM
authors.lastname: Sá
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D006801:Humans; D007550:Isothiuronium / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013890:Thiourea / Q000031:analogs & derivatives*
chemical_list: D000970:Antineoplastic Agents; D007550:Isothiuronium; D013890:Thiourea
keywords: Allylic bromides; Antitumor activity; DNA fragmentation; Isothiouronium salts; Leukemia