New iminodibenzyl derivatives with anti-leishmanial activity

Author(s)

Arndt, Anderson ; Liria, Cleber Wanderlei ; Yokoyama-Yasunaka, Jenicer K. U. ; Teresa Machini, M. ; Bortolin Uhana, Silvia Reni ; Esposito, Breno Pannia

• Document type: Journal article
• Source: Journal of Inorganic Biochemistry; v. 172, p. 9-15, JUL 2017.
• Web of Science Citations: 1

Abstract

Leishmaniasis is an infection caused by protozoa of the genus Leishmania and transmitted by sandflies. Current treatments are expensive and time-consuming, involving Sb(V)-based compounds, lipossomal amphotericin B and miltefosine. Recent studies suggest that inhibition of trypanothione reductase (TR) could be a specific target in the development of new drugs because it is essential and exclusive to trypanosomatids. This work presents the synthesis and characterization of new iminodibenzyl derivatives (dado) with ethylenediamine (ea), ethanolamine (en) and diethylenetriamine (dien) and their copper(II) complexes. Computational methods indicated that the complexes were highly lipophilic. Pro-oxidant activity assays by oxidation of the dihydrorhodamine (DHR) fluorimetric probe showed that {[}Cu(dado-ea)](2+) has the highest rate of oxidation, independent of H2O2 concentration. The toxicity to L. amazonensis promastigotes and RAW 264,7 macrophages was assessed, showing that dado-en was the most active new compound. Complexation to copper did not have an appreciable effect on the toxicity of the compounds. (AU)

• FAPESP's process: 16/03709-9 - Modulation of the levels and reactivity of physiological iron by mean of new natural or bifunctional chelators: possible applications in human health
• Grantee: Breno Pannia Esposito
• Support Opportunities: Regular Research Grants
• FAPESP's process: 11/50318-1 - Development of compounds with pharmacological or medicinal interest and of systems for their transport, detection and recognition in biological media
• Grantee: Ana Maria da Costa Ferreira
• Support Opportunities: Research Projects - Thematic Grants