Journal
JOURNAL OF INORGANIC BIOCHEMISTRY
Volume 103, Issue 1, Pages 128-134Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jinorgbio.2008.09.018
Keywords
2'-Deoxyguanosine analogue; Acyclovir-antiherpes agent; Palladium(II) complex; HSV-1 inhibitory activity
Funding
- Spanish Ministerio de Ciencia y Tecnologia [BQU/CTQ-2005-01834]
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Cytotoxicity and herpes simplex virus (HSV-1) inhibitory activity of acyclovir (ACV), 9-[(2-hydroxyethoxy)methyljguanine, and the palladium(II) coordination complex cis-[PdCl2(H2O)(N7-ACV)] center dot ACV center dot xH(2)O have been tested in African green monkey kidney (Vero line) epithelial cell cultures. The N(7) position of ACV represents the preferred binding site to afford a pseudo-chelate N7/O6 Pd(II) complex involving H-bonds with the cis H2O molecule. The Pd(II)-ACV complex has been structurally characterized by FTIR and H-1 NMR spectroscopy techniques, chemical composition was measured by elemental analysis, and the thermoanalytical study was performed by TG/DTA. The recognition of secondary ACV molecules by the Pd(II) derivative promotes cooperatively potent HSV-1 inhibitory activity which, in turn, strongly depends on concentration conditions. At the optimal concentration of 10 mu M, this complex exhibits antiviral efficiency in vitro, approximately hundred-fold (ca. 1.87 log(10)) more effective in herpes-infected cells when compared with that of the parent ACV molecules. The molecular-level observation of noticeable modifications caused by the complex on the morphology of the plasmid pBR322 DNA was monitored by AFM, whose mutual interaction evolves to eventually afford DNA condensates upon increasing the period of incubation. (c) 2008 Elsevier Inc. All rights reserved.
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