78582-01-1Relevant articles and documents
Chemo-enzymatic synthesis and biological evaluation of 5,6-disubstituted benzimidazole ribo- and 2′-deoxyribonucleosides
Konstantinova, Irina D.,Selezneva, Olga M.,Fateev, Ilja V.,Balashova, Tamara A.,Kotovskaya, Svetlana K.,Baskakova, Zoya M.,Charushin, Valery N.,Baranovsky, Alexander V.,Miroshnikov, Anatoly I.,Balzarini, Jan,Mikhailopulo, Igor A.
, p. 272 - 280 (2013)
A number of new 5,6-disubstituted benzimidazoles have been prepared and their substrate properties for recombinant E. coli purine nucleoside phosphorylase (PNP; the product of the deoD gene) in the transglycosylation reaction were investigated. The heterocyclic bases showed good substrate activity for PNP and the ribo- and 2-deoxyribonucleosides were synthesized. The predominant (OMe and OEt) or exclusive (Oi-Pr, morpholino, and N-methylpiperazino) formation of the 5-substituted 6-fluoro-1-(β-d- ribofuranosyl)benzimidazoles was observed. The formation of the regioisomeric 6- methoxy-, 6-ethoxy-, or 6-isopropoxy-substituted 1-(2-deoxy-β-d- ribofuranosyl)-5-fluorobenzimidazoles was observed in the trans-2- deoxyribosylation reaction of the corresponding bases. The predominant or exclusive formation of the regioisomeric N1-nucleosides with bulky 5-substituents of 6-fluorobenzimidazole points to a large hydrophobic pocket in the E. coli PNP active site that can accommodate these groups. The biological activity of the synthesized nucleosides was studied and revealed no inhibitory activity against a broad variety of DNA and RNA viruses. The compounds also lacked significant cytotoxicity. Georg Thieme Verlag Stuttgart New York.
