Synthesis and tripanocidal activity of ferrocenyl and benzyl diamines against Trypanosoma brucei and Trypanosoma cruzi

• Published in: Bioorganic & medicinal chemistry letters Vol. 24; no. 7; pp. 1707 - 1710
• Main Authors: Velásquez, Angela Maria Arenas, Francisco, Acácio Ivo, Kohatsu, Andréa Akiko Nakaima, Silva, Flavia Alves de Jesus, Rodrigues, Danilo Fernando, Teixeira, Rafaela Gomes da Silva, Chiari, Bruna Galdorfini, de Almeida, Maria Gabriela José, Isaac, Vera Lucia Borges, Vargas, Maria D., Cicarelli, Regina Maria Barretto
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-04-2014
• Subjects: Benzyl Compounds - chemical synthesis; Benzyl Compounds - chemistry; Benzyl Compounds - pharmacology; Benzyl diamines; Cell Survival - drug effects; Chagas disease; Diamines - chemical synthesis; Diamines - chemistry; Diamines - pharmacology; Dose-Response Relationship, Drug; Ferrocenyl diamines; Ferrous Compounds - chemical synthesis; Ferrous Compounds - chemistry; Ferrous Compounds - pharmacology; Hep G2 Cells; Humans; Metallocenes; Molecular Structure; Parasitic Sensitivity Tests; Sleeping sickness; Structure-Activity Relationship; Trypanocidal Agents - chemical synthesis; Trypanocidal Agents - chemistry; Trypanocidal Agents - pharmacology; Trypanosoma brucei; Trypanosoma brucei brucei - drug effects; Trypanosoma cruzi; Trypanosoma cruzi - drug effects; Chagas disease; Sleeping sickness; Benzyl diamines; Ferrocenyl diamines
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2014.02.046

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.