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Bioorganic & Medicinal Chemistry
Volume 15, Issue 14, 15 July 2007, Pages 4705-4713
 
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doi:10.1016/j.bmc.2007.05.005    How to Cite or Link Using DOI (Opens New Window)
Copyright © 2007 Elsevier Ltd All rights reserved.

Synthesis of neutral and cationic tripyridylporphyrin-d-galactose conjugates and the photoinactivation of HSV-1

João P.C. Toméa, Eduarda M.P. Silvaa, Ana M.V.M. Pereiraa, Cristina M.A. Alonsoa, Maria A.F. Faustinoa, Maria G.P.M.S. Nevesa, Augusto C. Toméa, José A.S. Cavaleiroa, Corresponding Author Contact Information, E-mail The Corresponding Author, Sabina A.P. Tavaresb, Ricardo R. Duarteb, Maria F. Caeiroc and Maria L. Valdeirab, maltese cross

aDepartment of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal bCenter of Molecular Pathogenesis, Faculty of Pharmacy, University of Lisbon, 1649-019 Lisbon, Portugal cUniversity of Lisbon, Faculty of Sciences, Department of Plant Biology, 1749-016 Lisbon, Portugal

Received 7 December 2006; 
revised 23 April 2007; 
accepted 2 May 2007. 
Available online 8 May 2007.

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Abstract

Neutral and cationic tripyridylporphyrin-d-galactose conjugates were synthesized and their antiviral activity against herpes simplex virus type 1 (HSV-1) was evaluated. At non-cytotoxic concentrations the studied compounds show significant antiviral activity after photoactivation. The influence of photoactivation on drug treated cells was also analyzed, at different times of infection with HSV-1, for a neutral (1b) and a cationic glycoporphyrin (3b) derivative. The results show that the inhibition of the viral yield is more dependent on photoactivation for compound 1b than for compound 3b. These two compounds also differ in the inhibitory effect during the viral replicative cycle: while compound 3b inhibits the viral yield at all the addition times assayed, compound 1b is more efficient in later times of infection.

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Keywords: Cationic porphyrins; Sugars; Antiviral compounds; HSV-1

Article Outline

1. Introduction
2. Chemistry
2.1. Results and discussion
3. Photophysical studies
3.1. Photostability of the compounds
3.2. Singlet oxygen production
4. Biological evaluation
4.1. Photocytotoxicity studies
4.2. Virucidal effect
4.3. Influence of the drug addition time on virus yield during infection
5. Discussion and conclusions
6. Experimental
6.1. General
6.2. Synthesis
6.2.1. 5-[4-(1,2:3,4-Di-O-isopropylidene-α-d-galactopyranosyl-6-oxycarbonyl)phenyl]-10,15,20-tri(4-pyridyl)porphyrin (1a)
6.2.2. 5-[4-(α/β-d-Galactopyranosyl-6-oxycarbonyl)phenyl]-10,15,20-tri(4-pyridyl)porphyrin (1b)
6.2.3. Methylation of porphyrins 1a and 1b
6.2.4. 5-[4-(1,2:3,4-Di-O-isopropylidene-α-d-galactopyranosyl-6-oxycarbonyl)phenyl]-10,15,20-Tris(N-methylpyridinium-4-yl)porphyrin tri-iodide (3a)
6.2.5. 5-[4-(α/β-d-Galactopyranosyl-6-oxycarbonyl)phenyl]-10,15,20-Tris(N-methylpyridinium-4-yl)porphyrin tri-iodide (3b)
6.3. Photostability of the porphyrin derivatives
6.4. Singlet oxygen generation
6.5. Photosensitizers
6.6. Cells and virus
6.7. Photocytotoxicity
6.8. Virucidal effect
6.9. Influence of the drug addition time on virus yield during infection
Acknowledgements
References






 
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