Synthesis and anti-herpes simplex viral activity of glycoglycerolipids

Abstract

This research was aimed to study the synthesis and anti-herpes simplex viral activity of glycoglycerolipids. A series of monoglycosyl glycerides bearing either glucose or galactose and related derivatives were synthesized. Thirty monoglycosyl glycerides bearing various chain lengths of saturated and unsaturated fatty acids were successfully prepared. Three monoglycerides and one diglyceride were also synthesized. Preliminary structure-activity relationships were reported. The chemical structures of the synthesized compounds were confirmed by spectroscopic techniques and elemental analysis. The anti-HSV activity was determined via the plaque reduction assay. Among the compounds synthesized, 1,2-di-O-linolenoyl-3-O-beta-D-glucopyranosyl-sn-glycerol shows the highest inhibitory activity against HSV-1 and HSV-2 with the IC[subscript 50] values of 16.1 and 23.9 micro-M, respectively. A study of the structure-activity relationships of these synthetic compounds indicates that the fatty acyl moieties are critical for inhibitory action with higher activity displayed as the acyl groups become more olefinic in character. The sugar moiety is also important for anti-HSV action; however, the type of sugar (glucose or galactose) exhibits no different activity. The stereochemistry at C-2 of the glycerol backbone displays no significant effect on anti-HSV activity.