title: Coordination of lapachol to bismuth(III) improves its anti-inflammatory and anti-angiogenic activities.
abstract: Complex [Bi(Lp)(2)]Cl was obtained with 4-hydroxy-3-(3-methylbut-2-enyl)naphthalene-1,2-dione, "lapachol" (HLp). Lapachol, [Bi(Lp)(2)]Cl and BiCl(3) were evaluated in a murine model of inflammatory angiogenesis induced by subcutaneous implantation of polyether polyurethane sponge discs. Intraperitoneal (i.p.) administration of lapachol or [Bi(Lp)(2)]Cl reduced the hemoglobin content in the implants suggesting that reduction of neo-vascularization was caused by lapachol. In the per os treatment only [Bi(Lp)(2)]Cl decreased the hemoglobin content in the implants. Likewise, N-acetylglucosaminidase (NAG) activity decreased in the implants of the groups i.p. treated with lapachol and [Bi(Lp)(2)]Cl while in the per os treatment inhibition was observed only for [Bi(Lp)(2)]Cl. Histological analysis showed that the components of the fibro-vascular tissue (vascularization and inflammatory cell population) were decreased in lapachol- and complex-treated groups. Our results suggest that both lapachol and [Bi(Lp)(2)]Cl exhibit anti-angiogenic and anti-inflammatory activities which have been attributed to the presence of the lapachol ligand. However, coordination to bismuth(III) could be an interesting strategy for improvement of lapachol's therapeutic properties.
authors.affiliation: Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil.
authors.forename: Gabrieli L
authors.initials: GL
authors.lastname: Parrilha
authors.forename: Rafael P
authors.initials: RP
authors.lastname: Vieira
authors.forename: Paula P
authors.initials: PP
authors.lastname: Campos
authors.forename: Grácia Divina F
authors.initials: GD
authors.lastname: Silva
authors.forename: Lucienir P
authors.initials: LP
authors.lastname: Duarte
authors.forename: Silvia P
authors.initials: SP
authors.lastname: Andrade
authors.forename: Heloisa
authors.initials: H
authors.lastname: Beraldo
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000627:therapeutic use; D001729:Bismuth / Q000737:chemistry*; D020007:Implants, Experimental; D007249:Inflammation / Q000188:drug therapy; D008297:Male; D051379:Mice; D015394:Molecular Structure; D009285:Naphthoquinones / Q000737:chemistry / Q000627:therapeutic use
chemical_list: D020533:Angiogenesis Inhibitors; D000893:Anti-Inflammatory Agents; D009285:Naphthoquinones; C008252:lapachol; D001729:Bismuth