Inevitable emergence of multi-drug resistant strains to current available drugs makes an impetus for finding new therapeutic agents against herpes simplex virus (HSV). In this study, a series of novel derivatives of Biginelli-type pyrimidines were evaluated as potential anti-HSV-1 compounds by plaque reduction method. The cellular toxicity was assessed by XTT proliferation assay. The time course of anti-HSV activity of the most active compound was studied to show the anti-viral effect in various intervals of replication cycle. Compounds 2, 6, 8, 11, 12, 17, 18, 20, and 40 had the highest activity for inhibition of HSV. Compound 40 inhibited HSV replication with IC50 of 0.9 μmol/l and had CC50 of up to 100 μmol/l. This compound was a noteworthy inhibitor against HSV with TI value of 111. Compound 20 also showed considerable inhibitory activity with IC50 of 1.8 μmol/l. Result of time-of-addition study showed that compound 40 inhibits HSV replication at a stage after entry of virions to the target cells. Analysis of structure of the studied compounds demonstrated clear relationships with their anti-HSV effects. Some of the compounds seem to be promising candidates for future anti-HSV drug discovery researches. Structural manipulation based on the obtained structure-activity relationships would propose some new leads for anti-HSV drug discovery programs. © 2012 Springer Science+Business Media, LLC.
|EMTREE drug terms:||antivirus agentpyrimidine derivative|
|EMTREE medical terms:||animal cellantiviral activityarticleBiginelli reactioncell assaycell proliferationconcentration responsecontrolled studydrug cytotoxicitydrug effectHerpes simplex virus 1IC 50nonhumanstructure activity relationtarget cellvirionvirus entryvirus inhibitionvirus replication|
Majidzadeh-A, K.; Tasnim Biotechnology Research Center, AJA University of Medical Sciences, Iran; email:[email protected]
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