New Limonene-Hybrid Derivatives with Anti-T. cruzi Activity

G. ÁLVAREZ, A. GERPE, D. BENITEZ, F. GARIBOTTO, S. ZACCHINO, C. S. GRAEBIN, R. GOMES DA ROSA, V. L. EIFLER-LIMA, M. GONZÁLEZ, AND H. CERECETTO.

LETTERS IN DRUG DESIGN & DISCOVERY

BENTHAM SCIENCE PUBL LTD

Año: 2010 vol. 7 p. 452 - 460

1570-1808

The development of hybrid compounds containing limonene- and recognized anti-T. cruzi-heterocycleframeworks is described. The six new compounds displayed broad antitrypanosomal activities having 5-nitrofuran and 5- nitroindazole derivatives, the best profiles. In addition, a 5-nitroindazole derivative evaluated against a panel of fungi exhibited relevant activities. Knowing that free-radical-production operates as one of the mechanisms of action on these heterocycles, we studied a potential extra-mechanism, membrane-sterols changes. Non-relevant T. cruzi squalene accumulation was observed for any of the tested hybrid-limonene derivatives.T. cruzi-heterocycleframeworks is described. The six new compounds displayed broad antitrypanosomal activities having 5-nitrofuran and 5- nitroindazole derivatives, the best profiles. In addition, a 5-nitroindazole derivative evaluated against a panel of fungi exhibited relevant activities. Knowing that free-radical-production operates as one of the mechanisms of action on these heterocycles, we studied a potential extra-mechanism, membrane-sterols changes. Non-relevant T. cruzi squalene accumulation was observed for any of the tested hybrid-limonene derivatives.T. cruzi squalene accumulation was observed for any of the tested hybrid-limonene derivatives.