In vitro activity of novel derivatives of 1,3-oxazole-4-carboxylate and 1,3-oxazole-4-carbonitrile against human cytomegalovirus

AbstractTen 5-functionalized derivatives of 1,3-oxazole-4-carboxylate and 1,3-oxazole-4-carbonitrile were synthesized and their antiviral activities against the human cytomegalovirus (HCMV) were evaluated in vitro. Bioassays showed that seven compounds exhibited considerably higher antiviral activity (EC50:  <  0.05 μM) against a normal laboratory HCMV strain (AD-169) in human foreskin fibroblast cells than Ganciclovir (EC50 = 0.32 μM), an anti-HCMV agent in clinical use. Additionally, the HCMV-resistant isolate (GDGr K17) was tested for sensitivity to 1,3-oxazole derivatives with most antiviral potency against the strain AD169. A one of them (5-((2-hydroxyethyl)(methyl)amino)-2-(4-methylphenyl)-1,3-oxazole-4-carbonitrile) showed very high potency (EC50:  <  0.05; CC50:>150  µM, and SI50 = 3125) towards the resistant isolate compared to standard drugs Cidofovir (EC50 = 0.10 µM, CC50:>30  µM and SI50:<4). But, in contrast to the primary assays, the antiviral activity of these compounds against both the normal strain and the resistant isolate of HCMV were considerably less than one of Cidofovir in secondary assay. These results provided evidence that derivatives of 1,3-oxazole could be useful for developing new anti-HCMV drugs.
Source: Medicinal Chemistry Research - Category: Chemistry Source Type: research