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. // SYNTHESIS-STUTTGART. - 2013. - V. 45, l. 2. - P. 272-280.

ISSN/EISSN:

0039-7881 / нет данных

Type:

Article

Abstract:

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-(beta-D-ribofuranosyl)benzimidazoles was observed. The formation of the regioisomeric 6- methoxy-, 6-ethoxy-, or 6-isopropoxy-substituted 1-(2-deoxy-beta-D-ribofuranosyl)-5-fluorobenzimidazoles was observed in the trans-2-deoxyribosylation reaction of the corresponding bases. The predominant or exclusive formation of the regioisomeric N-1-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.

Author keywords:

5,6-disubstituted benzimidazoles; purine nucleoside phosphorylase; substrate properties; transglycosylation reaction; nucleosides HUMAN CYTOMEGALOVIRUS; ENZYMATIC TRANSGLYCOSYLATION; ANTIVIRAL DRUGS; MARIBAVIR; BIOTECHNOLOGY

DOI:

10.1055/s-0032-1317782

Web of Science ID:

ISI:000313362800019

Соавторы в МНС:

—

Другие поля

Поле	Значение
Month	JAN
Publisher	GEORG THIEME VERLAG KG
Address	RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
Language	English
Keywords-Plus	HUMAN CYTOMEGALOVIRUS; ENZYMATIC TRANSGLYCOSYLATION; ANTIVIRAL DRUGS; MARIBAVIR; BIOTECHNOLOGY
Research-Areas	Chemistry
Web-of-Science-Categories	Chemistry, Organic
Author-Email	imikhailopulo@gmail.com
ResearcherID-Numbers	Miroshnikov, Anatoly/G-5017-2017
Funding-Acknowledgement	International Science and Technology Centre {[}B-1640]; Ministry of Education and Science of Russian Federation {[}02.740.11.0260]; KU Leuven {[}GOA 10/14]
Funding-Text	Financial support by the International Science and Technology Centre (project \#B-1640), the Ministry of Education and Science of Russian Federation, State Contract 02.740.11.0260, and the KU Leuven (GOA 10/14) are gratefully acknowledged. The authors are indebted to Dr. Roman S. Esipov (Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow) for supplying the recombinant E. coli nucleoside phosphorylases.
Number-of-Cited-References	28
Usage-Count-Since-2013	13
Journal-ISO	Synthesis
Doc-Delivery-Number	068JK