Activity of a hydroxybibenzyl bryophyte constituent against Leishmania spp. and Trypanosoma cruzi: in silico, in vitro and in vivo activity studies.
The synthesis and potent antiprotozoal activity of 14-hydroxylunularin, a natural hydroxybibenzyl bryophyte constituent is reported. 14-hydroxylunularin was highly active in vitro assays against culture and intracellular forms of Leishmania spp. and Trypanosoma. cruzi, in absence of cytotoxicity against mammalian cells. Preliminary structure-activity relationship studies showed that the reported bioactivity depends on hybridization at the carbon-carbon bridge, position and number of free hydroxy group on the aromatic rings. The reported results were also in agreement with the in silico prediction using Non-Stochastic Quadratic Fingerprints-based algorithms. The same compound also showed antiprotozoal activity in Leishmania spp. infected mice by oral and subcutaneous administration routes, with an optimal treatment of a daily subcutaneous administration of 10 mg/kg of body weight for 15 days. This study suggested that 14-hydroxylunularin may be chosen as a new candidate in the development of leishmanicidal therapy.
Roldos
Virginia
V
Departamento de Química Orgánica, Facultad de Química, Universidad de la República, Av.Gral. Flores 2124, CC 1157, Montevideo 11800, Uruguay.
Nakayama
Hector
H
Rolón
Miriam
M
Montero-Torres
Alina
A
Trucco
Fernando
F
Torres
Susana
S
Vega
Celeste
C
Marrero-Ponce
Yovanni
Y
Heguaburu
Viviana
V
Yaluff
Gloria
G
Gómez-Barrio
Alicia
A
Sanabria
Luis
L
Ferreira
Maria Elena
ME
Rojas de Arias
Antonieta
A
Pandolfi
Enrique
E
D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D001632:Bibenzyls / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002417:Cattle; D002460:Cell Line; D019295:Computational Biology; D005110:Extracellular Space / Q000187:drug effects; D005260:Female; D020128:Inhibitory Concentration 50; D042541:Intracellular Space / Q000187:drug effects; D007891:Leishmania / Q000166:cytology / Q000187:drug effects*; D007896:Leishmaniasis / Q000188:drug therapy; D008297:Male; D051379:Mice; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D014349:Trypanosoma cruzi / Q000187:drug effects*
C533393:14-hydroxylunularin; D000981:Antiprotozoal Agents; D001632:Bibenzyls; D010636:Phenols