RESUMEN
Antiherpetic activity of the double and triple combinations, including original connections 15Lys-bis-Nt and phosphate of acycloguanosine (P-ACG), was studied in vitro. For the first time, it was demonstrated that in case of their combined use with known antiherpetic agents, whose activity does not depend on TK of HSV (PFA, AraA, CDV, Rib, GLN, αa-IFN), synergistic or additive effects of interaction was observed. The antiviral effect of the tested combinations was studied on the model of ACG-resistant viral strain. The tested combinations could be of interest for practical medicine.
Asunto(s)
Herpes Simple/tratamiento farmacológico , Simplexvirus/efectos de los fármacos , Simplexvirus/genética , Replicación Viral/efectos de los fármacos , Aciclovir/administración & dosificación , Animales , Antivirales/administración & dosificación , Chlorocebus aethiops , Farmacorresistencia Viral/efectos de los fármacos , Farmacorresistencia Viral/genética , Sinergismo Farmacológico , Herpes Simple/genética , Herpes Simple/virología , Simplexvirus/crecimiento & desarrollo , Células VeroRESUMEN
New non-nucleoside esters of phosphoric acid containing various hydrophobic groups, namely (1) N-(2-tripticencarbonyl)-4-aminobutyl; (2) 5-phenylsubstituted N-(2,4-dinitrophenyl)-4-aminobutyl; (3) N-(4-phenylbenzoyl)- and N-(4-(N-benzylamino)benzoyl)-2-aminoethyl groups, as well as (4) diphenylmethyl and fluorenyl groups were synthesized and studied as substrates of terminal deoxynucleotidyl transferase. With the exception of the two latter derivatives, all the analogues displayed substrate properties and could incorporate into the deoxyoligonucleotide 3'-end. As it was shown in biochemical experiments and by computer modeling, a linker joining the triphosphate and hydrophobic fragments of the molecule was necessary for these compounds to display substrate properties.