Synthesis of naphthofuranquinones with activity against Trypanosoma cruzi.
Four new naphthofuranquinones, obtained from 2-hydroxy-3-allyl-naphthoquinone (1) and nor-lapachol (2), have their structures established by physical and X-ray analysis and their activity evaluated against Trypanosoma cruzi. Compounds 3 and 4 were obtained by addition of iodine to 1 followed by cyclization generating a furan ring. Compound 5 was obtained through the acid-catalyzed reaction by dissolution of 1 in sulfuric acid. Compound 6 was synthesized by addition of bromine and aniline to 2. The IC(50)/24 h for 3-6 in assays with T. cruzi trypomastigotes was between 157 and 640 microM, while the value for crystal violet was 536.0 +/- 3.0 microM. Compounds 3-5 also inhibited epimastigote proliferation. The trypanocidal activity of the new naphthofuranquinones endowed with redox properties reinforces a rational approach in the chemotherapy of Chagas' disease.
Silva
Raphael S F
RS
Núcleo de Pesquisas em Produtos Naturais, CCS, Universidade Federal do Rio de Janeiro, Brazil.
Costa
Elaine M
EM
Trindade
Ursula L T
UL
Teixeira
Daniel V
DV
Pinto
Maria de Carmo F R
Mde C
Santos
Gustavo L
GL
Malta
Valeria R S
VR
De Simone
Carlos Alberto
CA
Pinto
Antonio Ventura
AV
de Castro
Solange L
SL
D000818:Animals; D003460:Crystallization; D018360:Crystallography, X-Ray; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008958:Models, Molecular; D009285:Naphthoquinones / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects*
D007202:Indicators and Reagents; D009285:Naphthoquinones; D014344:Trypanocidal Agents