Synthesis and antiprotozoal activity of naphthofuranquinones and naphthothiophenequinones containing a fused thiazole ring.
The synthesis of tetracyclic quinones 10a,b, 14a,b, 19a,b and 20a,b is described. The preparations involve regioselective Diels-Alder reactions via trapping the thiazole o-quinodimethane 9 with several benzofuranquinones and benzothiophenequinones. The structure of the regioisomers was assigned through 2D NMR 1H-13C HMBC experiments performed on 10a and 14a. Compounds 10a,b, 14a as well as phenol 1 and the starting quinones 2, 5, 7 and 15 are evaluated against Leishmania sp., Toxoplasma gondii and THP-1 cells. Almost all the tested compounds exhibit significant antiprotozoal activities with lower cytotoxicities than the reference compounds. Among them, quinones 2 and 14a possess the best activities towards L. donovani and T. gondii with the lowest toxicities.
Tapia
Ricardo A
RA
Facultad de Química, Pontificia Universidad Católica de Chile, Correo 22, Santiago, Chile. rtapia@puc.cl
Alegria
Luz
L
Pessoa
Carlos D
CD
Salas
Cristian
C
Cortés
Manuel J
MJ
Valderrama
Jaime A
JA
Sarciron
Marie Elisabeth
ME
Pautet
Félix
F
Walchshofer
Nadia
N
Fillion
Houda
H
D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D005663:Furans / Q000737:chemistry; D006801:Humans; D007893:Leishmania donovani / Q000187:drug effects*; D015394:Molecular Structure; D022423:Myeloid Cells / Q000187:drug effects / Q000469:parasitology; D009285:Naphthoquinones / Q000138:chemical synthesis* / Q000494:pharmacology; D021261:Parasitic Sensitivity Tests; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry; D013876:Thiophenes / Q000737:chemistry; D014122:Toxoplasma / Q000187:drug effects*
D000981:Antiprotozoal Agents; D005663:Furans; D009285:Naphthoquinones; D013844:Thiazoles; D013876:Thiophenes