Synthesis and anti-herpes simplex viral activity of monoglycosyl diglycerides.
Based on the discovery of antiviral beta-galactosyl diglycerides from Clinacanthus nutans leaves, 19 monoglycosyl diglycerides were synthesized and examined for inhibitory effect on herpes simplex virus types 1 and 2 (HSV-1, HSV-2). A study of the structure-activity relationships of the synthetic monoglycosyl diglycerides indicated that the fatty acyl moieties were critical for inhibitory action with higher activity displayed as the acyl groups became more olefinic in character. The sugar moiety was also important for anti-HSV action; however, the type of sugar (glucose or galactose) did not affect activity. The stereochemistry at C-2 of the glycerol backbone displayed no significant effect on anti-HSV activity. Among the compounds synthesized, 1,2-O-dilinolenoyl-3-O-beta-D-glucopyranosyl-sn-glycerol showed the highest inhibitory activity against HSV-1 and HSV-2 with IC50 values of 12.5+/-0.5 and 18.5+/-1.5 microg/ml, respectively.
Janwitayanuchit
Wicharn
W
Faculty of Pharmaceutical Sciences, Chulalongkorn University Bangkok, 10330, Thailand.
Suwanborirux
Khanit
K
Patarapanich
Chamnan
C
Pummangura
Sunibhond
S
Lipipun
Vimolmas
V
Vilaivan
Tirayut
T
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D004075:Diglycerides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006031:Glycosylation; D018259:Herpesvirus 1, Human / Q000187:drug effects*; D018258:Herpesvirus 2, Human / Q000187:drug effects*; D020128:Inhibitory Concentration 50; D019906:Nuclear Magnetic Resonance, Biomolecular; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D004075:Diglycerides