ABSTRACT
By screening a library of sulphated compounds of low molecular weight, we have found that several cyclitol derivatives, each modified with two sulphate groups in addition to pyrrole and various aromatic moieties, inhibited infectivity of herpes simplex virus (HSV) at concentrations approximately 100 times lower than those toxic for cultured cells. These disulphated cyclitols interfered with HSV-1 attachment to cells, and efficiently reduced the cell-to-cell spread of the virus. This effect is most likely due to their low molecular weight and associated with the compounds' capability to access the narrow intercellular spaces. Furthermore, these disulphated cyclitols also inactivated infectivity of HSV. However, the virus-inactivating activities of these compounds were to some extent diminished in the presence of human cervical secretions or other protein-rich solutions suggesting that disulphated cyclitols may have some features of surfactant-type virucides. In conclusion, this new class of anti-HSV compounds offers potential for further development.
Subject(s)
Antiviral Agents/pharmacology , Polysaccharides/pharmacology , Simplexvirus/drug effects , Animals , Cell Line , Chlorocebus aethiops , Magnetic Resonance Spectroscopy , Simplexvirus/growth & development , Simplexvirus/isolation & purification , Viral Plaque AssayABSTRACT
Palladium[0]-mediated Ullmann cross-coupling of 1-bromo-2-nitrobenzene (1 R = H) and its derivatives with a range of beta-halo-enals, -enones, or -esters readily affords the corresponding beta-aryl derivatives, which are converted into the corresponding quinolines, 2-quinolones, phenanthridines, or 6(5H)-phenanthridinones on reaction with dihydrogen in the presence of Pd on C or with TiCl(3) in aqueous acetone. [reaction: see text]
ABSTRACT
Treatment of readily available o-(buta-1,3-diyn-1-yl-)-substituted N-aryl ureas such as 1 with the Au(I)-catalyst 11 affords, via a twofold cyclization process, the isomeric pyrimido[1,6-a]indol-1(2H)-one 3 in good yield.