Trypanocidal activity of isolated naphthoquinones from Tabebuia and some heterocyclic derivatives: A review from an interdisciplinary study

Naphthoquinones isolated from the wood of trees of the families Bignoniacea e and Verbenaceae have been subjected to an interdisciplinary study since t he seventies, when Dr. Benjamin Gilbert, at the Federal University of Rio d e Janeiro, launched a program on the chemistry of natural products active a gainst endemic diseases. In this paper we describe the synthesis of five na phthoimidazoles, derived from this program and their activity towards T. cr uzi, the etiologic agent of Chagas disease. We also review the influence of chemical structure on trypanocidal action of naphthoquinones and of derive d heterocycles with imidazole, oxazole, phenoxazine, indole, dipyrane and c yclopentene rings. The overall analysis corroborates the tendency of trypan ocidal activity in compounds with an imidazole or oxazole ring linked to a naphthopyrane structure. Two naphthoimidazoles presented higher activities (14.5x and 34.8x) than the standard crystal violet. Emphasis is given to th e biodiversity of the Brazilian flora as a starting point for the developme nt of an autonomous and creative medicinal chemistry.