Trypanocidal activity of synthetic heterocyclic derivatives of active quinones from Tabebuia sp.
Continuing a program on the chemistry and biological activity of compounds from the Brazilian flora, the lytic activity against bloodstream forms of T. cruzi of nine new heterocyclic naphthooxazole and naphthoimidazole derivatives obtained from the reaction of naphtoquinones isolated from Tabebuia sp. (Tecoma) with amino-containing reagents has been studied. Also for the first time the biological activity of allyl derivatives of lawsone, a natural quinone from Lausonia alba inactive against T. cruzi, is reported. The introduction of an allyl group in lawsone gives rise to O-allyl-lawsone and C-allyl-lawsone that showed activity against the parasite, with ID50 values of 420.7 +/- 71.1 and 330.7 +/- 62.4 mumol/l, respectively. The trypanocidal activity of the naphtho heterocyclics synthesized from the original quinones showed no concordant behavior in relation to the parent compound. Six of nine of the synthesized compounds presented lower ID50 values than crystal violet, indicating a general trend of activity among naphthalenic heterocyclics of the oxazole/imidazole type. However, their chemical structures do not endow them with the capacity of free radical generation by biological reduction as the quinoidal moiety, nor do they have chemical reducible appendage like the nitro group of nifurtimox and benznidazole, responsible for such behaviour. As a hypothesis, the pattern of their biological actions should be focused in other aspects of their chemical structures. Because of their polycyclic planar topology, these derivatives are potential candidates for experimental tests as DNA intercalating agents.
Pinto
A V
AV
Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Brazil.
Pinto
C N
CN
Pinto
M do C
Mdo C
Rita
R S
RS
Pezzella
C A
CA
de Castro
S L
SL
D000818:Animals; D001938:Brazil; D014355:Chagas Disease / Q000188:drug therapy / Q000469:parasitology; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D007364:Intercalating Agents / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D009285:Naphthoquinones / Q000138:chemical synthesis / Q000494:pharmacology; D010946:Plants, Medicinal / Q000737:chemistry*; D011809:Quinones / Q000138:chemical synthesis* / Q000302:isolation & purification / Q000494:pharmacology; D013055:Spectrophotometry, Infrared; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000187:drug effects
D006571:Heterocyclic Compounds; D007364:Intercalating Agents; D009285:Naphthoquinones; D011809:Quinones; D014344:Trypanocidal Agents; C005090:lawsone