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Toward a novel metal-based chemotherapy against t... [J Med Chem. 2004] - PubMed - NCBI

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Abstract

J Med Chem. 2004 Oct 7;47(21):5204-9.

Toward a novel metal-based chemotherapy against tropical diseases. 7. Synthesis and in vitro antimalarial activity of new goldchloroquine complexes.
Navarro M, Vsquez F, Snchez-Delgado RA, Prez H, Sinou V, Schrvel J.
Transition Metal Chemistry and Inmunoparasitology Laboratories, Instituto Venezolano de Investigaciones Cientificas (IVIC), Apartado 28127, 1020-A Caracas,Venezuela.

Abstract
A number of new Au(I) and Au(III) complexes of chloroquine (CQ) have been prepared, characterized, and evaluated in vitro against several strains of Plasmodium falciparum. [(CQ)Au(PPh(3))][NO(3)] (2) was synthesized by reaction of AuCl(PPh(3)) with AgNO(3) followed by treatment with CQ. Similar reactions of AuCl(PR(3)) (R = Me, Et) with KPF(6) and CQ yielded [(CQ)Au(PMe(3))][PF(6)] (3), and [(CQ)Au(PEt(3))][PF(6)] (4), respectively. KAuCl(4) reacted with CQ to produce the Au(III) complex [(CQ)(2)Au(Cl)(2)]Cl (5), which in turn formed [(CQ)Au(Cl)(SR)(Et(2)O)]Cl (6) by reaction with 1-thiobeta-d-glucose-2,3,4,6-tetraacetate (SRH). The new compounds were characterized by a combination of elemental analysis, fast atom bombardment mass spectrometry (FAB-MS), and NMR spectroscopy. All the complexes display in vitro activity against CQ-sensitive and CQ-resistant strains of Plasmodium falciparum. The highest activity for this series was obtained for complex 4, which is 5 times more active than chloroquine diphosphate (CQDP) against the CQ-resistant strain FcB1. On preincubation of noninfected red blood cells with complexes 1, 5, and 6, protection against subsequent infection was observed in some cases. No clear structure-activity correlations could be established for this series of compounds.
PMID: 15456263 [PubMed - indexed for MEDLINE]

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www.ncbi.nlm.nih.gov/pubmed/15456263

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