Synthesis and anti-Trypanosoma cruzi activity of derivatives from nor-lapachones and lapachones.
New naphthoquinone derivatives were synthesized and assayed against bloodstream trypomastigote forms of Trypanosoma cruzi, the etiological agent of Chagas' disease. The compounds were rationalized based on hybrid drugs and appear as important compounds against this parasite. From nor-lapachol were prepared five substituted ortho-naphthofuranquinones, a non-substituted para-naphthofuranquinone, a new oxyrane and an azide and from alpha-lapachone a new non-substituted para-naphthofuranquinone. Other five substituted ortho-naphthofuranquinones recently designed as cytotoxic, were also evaluated. The most active compounds were the ortho naphthofuranquinones 3-(4-methoxyphenylamino)-2,3-dihydro-2,2-dimethylnaphtho[1,2-b]furan-4,5-dione and 3-(3-nitrophenylamino)-2,3-dihydro-2,2-dimethylnaphtho[1,2-b]furan-4,5-dione with trypanocidal activity higher than that of benznidazole, the standard drug. The compounds were rationalized based on hybrid drugs and appear as important compounds against T. cruzi. The trypanocidal activity of these substances endowed with redox properties representing a good starting point for a medicinal chemistry program aiming the chemotherapy of Chagas' disease.
da Silva Júnior
Eufrânio N
EN
Departamento de Química Orgânica, Instituto de Química, UFF, 24020-150 Niterói, RJ, Brazil.
de Souza
Maria Cecília B V
MC
Fernandes
Michelle C
MC
Menna-Barreto
Rubem F S
RF
Pinto
Maria do Carmo F R
Mdo C
de Assis Lopes
Francisco
F
de Simone
Carlos Alberto
CA
Andrade
Carlos Kleber Z
CK
Pinto
Antônio V
AV
Ferreira
Vitor F
VF
de Castro
Solange L
SL
D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D015394:Molecular Structure; D009285:Naphthoquinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D021261:Parasitic Sensitivity Tests; D013237:Stereoisomerism; D014349:Trypanosoma cruzi / Q000187:drug effects*
D000981:Antiprotozoal Agents; D009285:Naphthoquinones; C415043:alpha-lapachone