RESUMEN
A new self-assembly method is used to rapidly functionalize the surface of liposomes without perturbing the membrane integrity or causing leakage of the aqueous contents. The key molecule is a cholesterol-squaraine-PEG conjugate with three important structural elements: a cholesterol membrane anchor, a fluorescent squaraine docking station that allows rapid and high-affinity macrocycle threading, and a long PEG-2000 chain to provide steric shielding of the decorated liposome. The two-step method involves spontaneous insertion of the conjugate into the outer leaflet of pre-formed liposomes followed by squaraine threading with a tetralactam macrocycle that has appended targeting ligands. A macrocycle with six carboxylates permitted immobilization of intact fluorescent liposomes on the surface of cationic polymer beads, whereas a macrocycle with six zinc(II)-dipicolylamine units enabled selective targeting of anionic membranes, including agglutination of bacteria in the presence of human cells.
Asunto(s)
Colorantes Fluorescentes/química , Liposomas/química , Polietilenglicoles/química , Aglutinación , Colesterol/química , Ciclobutanos/química , Transferencia Resonante de Energía de Fluorescencia , Humanos , Células Jurkat , Ligandos , Liposomas/metabolismo , Microscopía Fluorescente , Compuestos Organometálicos/química , Fenoles/química , Fosfatidilcolinas/química , Picolinas/química , Polímeros/química , Staphylococcus aureus/química , Staphylococcus aureus/metabolismoRESUMEN
This study measured the antiplasmodial activity of nine zinc-dipicolylamine (ZnDPA) complexes against three strains of Plasmodium falciparum, the causative parasite of malaria. Growth inhibition assays showed significant activity against all tested strains, with 50% inhibitory concentrations between 5 and 600nM and almost no toxic effect against host cells including healthy red blood cells. Fluorescence microscopy studies with a green-fluorescent ZnDPA probe showed selective targeting of infected red blood cells. The results suggest that ZnDPA coordination complexes are promising antiplasmodial agents with potential for targeted malaria treatment.
Asunto(s)
Antimaláricos/química , Complejos de Coordinación/química , Compuestos Organometálicos/química , Picolinas/química , Animales , Antimaláricos/síntesis química , Antimaláricos/uso terapéutico , Antimaláricos/toxicidad , Células CHO , Proliferación Celular/efectos de los fármacos , Complejos de Coordinación/síntesis química , Complejos de Coordinación/uso terapéutico , Complejos de Coordinación/toxicidad , Cricetinae , Cricetulus , Eritrocitos/efectos de los fármacos , Eritrocitos/parasitología , Hemólisis/efectos de los fármacos , Humanos , Malaria/tratamiento farmacológico , Microscopía Fluorescente , Plasmodium falciparum/efectos de los fármacosRESUMEN
Crystals of the title compound, C(18)H(30)N(6)·2H(2)O, are composed of units of diimidazo[c,h][1,6]diazecine and two water mol-ecules. The asymmetric unit contains one half-molecule of diazecine and one uncoordinated water molecule in a general position. The complete ten-membered heterocycle is generated by an inversion center.The organic residue and water mol-ecules form a two-dimensional hydrogen-bonded network. The 1,6-diazecine ring shows a chair conformation, with angles and distances in normal ranges.