Chemical reactivity studies with naphthoquinones from tabebuia with anti-trypanosomal efficacy

The biological activities of the naphthoquinones lapachol and its cyclizati on product beta -lapachone, extracted from trees of the genus Tabebuia, hav e been intensively studied. Given continuity to the studies about heterocyc lic derivatives obtained from the reaction of these naphtoquinones with ami no-containing reagents, 22 derivatives of beta -lapachone, nor-beta -lapach one and lapachol were synthesised and their activities against trypomastigo te forms of T. cruzi were evaluated. The compounds were grouped as oxazolic , imidazolic, phenoxazinic, indolic, pyranic and cyclopentenic derivatives. The variability of the new structures is based on the great electrophilici ty of 1,3-quinoidal carbonyls towards reagents containing nitrogen or carbo n as nucleophilic centres. In relation to the trypanocidal activity of the synthesised compounds, in view of their structural diversity, tendencies on ly could be verified. Among the cyclofunctionalised products the oxazolic a nd imidazolic derivatives showed +/- 1.5 to 34.8 times higher activity than crystal violet, the standard drug for the sterilization of stored blood. T hese results corroborate the tendency of trypanocidal activity in imidazoli c skeletons, and indicate that this moiety could be used as a guide for arc hitectural delineation of molecules with potential value for the chemothera py of Chagas disease.