title: Synthesis and biological evaluation of novel ferrocene-naphthoquinones as antiplasmodial agents.
abstract: This work deals with the synthesis and evaluation of new compounds designed by combination of 1,4-naphthoquinone and ferrocene fragments in a 3-ferrocenylmethyl-2-hydroxy-1,4-naphthoquinone arrangement. A practical coupling reaction between 2-hydroxy-1,4-naphthoquinone and ferrocenemethanol derivatives has been developed. This procedure can be carried out "on-water", at moderate temperatures and without auxiliaries or catalysts, with moderate to high yields. The synthesized derivatives have shown significant in vitro antiplasmodial activity against chloroquine-sensitive and resistant Plasmodium falciparum strains and it has been shown that this activity is not related to the inhibition of biomineralization of ferriprotoporphyrin IX. Binding energy calculations and docking of these compounds to cytochrome b in comparison with atovaquone have been performed.
authors.affiliation: Centro de Investigaciones en Productos Naturales and Escuela de Química, Universidad de Costa Rica, San Pedro 2060, San José, Costa Rica. Electronic address: pedro.garcia_b@ucr.ac.cr.
authors.forename: Pedro M
authors.initials: PM
authors.lastname: García-Barrantes
authors.forename: Guy V
authors.initials: GV
authors.lastname: Lamoureux
authors.forename: Alice L
authors.initials: AL
authors.lastname: Pérez
authors.forename: Rory N
authors.initials: RN
authors.lastname: García-Sánchez
authors.forename: Antonio R
authors.initials: AR
authors.lastname: Martínez
authors.forename: Arturo
authors.initials: A
authors.lastname: San Feliciano
mesh_terms: D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005296:Ferrous Compounds / Q000737:chemistry / Q000494:pharmacology*; D000075163:Metallocenes; D008958:Models, Molecular; D015394:Molecular Structure; D009285:Naphthoquinones / Q000737:chemistry / Q000494:pharmacology*; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*
chemical_list: D000962:Antimalarials; D005296:Ferrous Compounds; D000075163:Metallocenes; D009285:Naphthoquinones; C004998:ferrocene
keywords: Antimalarial; FBIT; Ferrocene; Lawsone; Naphthoquinone; On-water reactions; SI; ferriprotoporphyrin IX biomineralization inhibition test; selectivity index