Design of xanthone propionate photolabile protecting group releasing acyclovir for the treatment of ocular herpes simplex virus.
We have attached the antiviral drug acyclovir (ACV) to a xanthone photolabile protecting group (or photocage) through the O6 position of acyclovir, a procedure designed for the treatment of ocular herpes simplex virus infections. Acyclovir is photoreleased from the photocage, under physiological conditions, with a quantum yield (Φ(ACV release)) of 0.1-0.3 and an uncaging cross section (Φ·ε) of 450-1350 M cm(-1). We demonstrate that this photorelease method outcompetes alternative reaction pathways, such as protonation. Furthermore, complete release of the drug is theoretically possible given a sufficient dose of light . Surprisingly the acyclovir photocage, also showed some antiviral activity towards HSV-1.
Department of Chemistry, University of Ottawa, Ottawa, Canada.
Jessie A
JA
Blake
Bettina
B
Bareiss
Liliana
L
Jimenez
May
M
Griffith
J C
JC
Scaiano
D000212:Acyclovir / Q000737:chemistry / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000737:chemistry / Q000627:therapeutic use*; D016849:Keratitis, Herpetic / Q000188:drug therapy*; D015394:Molecular Structure; D010782:Photolysis; D011422:Propionates / Q000138:chemical synthesis / Q000737:chemistry*; D014466:Ultraviolet Rays; D044004:Xanthones / Q000138:chemical synthesis / Q000737:chemistry*
D000998:Antiviral Agents; D011422:Propionates; D044004:Xanthones; C009689:xanthone; D000212:Acyclovir