title: Synthesis and tripanocidal activity of ferrocenyl and benzyl diamines against Trypanosoma brucei and Trypanosoma cruzi.
abstract: Trypanosoma brucei and Trypanosoma cruzi are the etiologic agents of sleeping sickness and Chagas disease, respectively, two of the 17 preventable tropical infectious diseases (NTD) which have been neglected by governments and organizations working in the health sector, as well as pharmaceutical industries. High toxicity and resistance are problems of the conventional drugs employed against trypanosomiasis, hence the need for the development of new drugs with trypanocidal activity. In this work we have evaluated the trypanocidal activity of a series of N1,N2-dibenzylethane-1,2-diamine hydrochlorides (benzyl diamines) and N1-benzyl,N2-methyferrocenylethane-1,2-diamine hydrochlorides (ferrocenyl diamines) against T. brucei and T. cruzi parasite strains. We show that incorporation of the ferrocenyl group into the benzyl diamines increases the trypanocidal activity. The molecules exhibit potential trypanocidal activity in vitro against all parasite strains. Cytotoxicity assay was also carried out to evaluate the toxicity in HepG2 cells.
authors.affiliation: Departamento de Ciências Biológicas, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista 'Júlio de Mesquita Filho', Rodovia Araraquara-Jaú Km 01-Campus, Araraquara 14.801-902, Brazil; Instituto de Química, Universidade Estadual Paulista 'Júlio de Mesquita Filho', Rua Prof. Francisco Degni, 55, Araraquara 14.800-900, Brazil. Electronic address: avellangel@gmail.com.
authors.forename: Angela Maria Arenas
authors.initials: AM
authors.lastname: Velásquez
authors.affiliation: Instituto de Química, Universidade Federal Fluminense, Campus do Valonguinho-Centro, Niterói 24.020-150, Brazil.
authors.forename: Acácio Ivo
authors.initials: AI
authors.lastname: Francisco
authors.affiliation: Departamento de Ciências Biológicas, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista 'Júlio de Mesquita Filho', Rodovia Araraquara-Jaú Km 01-Campus, Araraquara 14.801-902, Brazil.
authors.forename: Andréa Akiko Nakaima
authors.initials: AA
authors.lastname: Kohatsu
authors.affiliation: Departamento de Ciências Biológicas, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista 'Júlio de Mesquita Filho', Rodovia Araraquara-Jaú Km 01-Campus, Araraquara 14.801-902, Brazil.
authors.forename: Flavia Alves de Jesus
authors.initials: FA
authors.lastname: Silva
authors.affiliation: Departamento de Ciências Biológicas, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista 'Júlio de Mesquita Filho', Rodovia Araraquara-Jaú Km 01-Campus, Araraquara 14.801-902, Brazil; Instituto de Química, Universidade Estadual Paulista 'Júlio de Mesquita Filho', Rua Prof. Francisco Degni, 55, Araraquara 14.800-900, Brazil.
authors.forename: Danilo Fernando
authors.initials: DF
authors.lastname: Rodrigues
authors.affiliation: Instituto de Química, Universidade Federal Fluminense, Campus do Valonguinho-Centro, Niterói 24.020-150, Brazil.
authors.forename: Rafaela Gomes da Silva
authors.initials: RG
authors.lastname: Teixeira
authors.affiliation: Departamento de Fármacos e Medicamentos, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista 'Júlio de Mesquita Filho', Rodovia Araraquara-Jaú Km 01-Campus, Araraquara 14.801-902, Brazil.
authors.forename: Bruna Galdorfini
authors.initials: BG
authors.lastname: Chiari
authors.affiliation: Departamento de Fármacos e Medicamentos, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista 'Júlio de Mesquita Filho', Rodovia Araraquara-Jaú Km 01-Campus, Araraquara 14.801-902, Brazil.
authors.forename: Maria Gabriela José
authors.initials: MG
authors.lastname: de Almeida
authors.affiliation: Departamento de Fármacos e Medicamentos, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista 'Júlio de Mesquita Filho', Rodovia Araraquara-Jaú Km 01-Campus, Araraquara 14.801-902, Brazil.
authors.forename: Vera Lucia Borges
authors.initials: VL
authors.lastname: Isaac
authors.affiliation: Instituto de Química, Universidade Federal Fluminense, Campus do Valonguinho-Centro, Niterói 24.020-150, Brazil.
authors.forename: Maria D
authors.initials: MD
authors.lastname: Vargas
authors.affiliation: Departamento de Ciências Biológicas, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista 'Júlio de Mesquita Filho', Rodovia Araraquara-Jaú Km 01-Campus, Araraquara 14.801-902, Brazil. Electronic address: reginacicarelli@gmail.com.
authors.forename: Regina Maria Barretto
authors.initials: RM
authors.lastname: Cicarelli
mesh_terms: D001593:Benzyl Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D003959:Diamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005296:Ferrous Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D000075163:Metallocenes; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014346:Trypanosoma brucei brucei / Q000187:drug effects*; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D001593:Benzyl Compounds; D003959:Diamines; D005296:Ferrous Compounds; D000075163:Metallocenes; D014344:Trypanocidal Agents; C004998:ferrocene
keywords: Benzyl diamines; Chagas disease; Ferrocenyl diamines; Sleeping sickness