Isomeric Naphtho-Fused 7-Deazapurine Nucleosides and Nucleotides: Synthesis, Biological Activity, Photophysical Properties and Enzymatic Incorporation to Nucleic Acids

0495509 - ÚOCHB 2019 RIV DE eng J - Journal Article
Ghosh, Ketaki - Perlíková, Pavla - Havlíček, Vojtěch - Yang, Chao - Pohl, Radek - Tloušťová, Eva - Hodek, Jan - Gurská, S. - Džubák, P. - Hajdúch, M. - Hocek, Michal
Isomeric Naphtho-Fused 7-Deazapurine Nucleosides and Nucleotides: Synthesis, Biological Activity, Photophysical Properties and Enzymatic Incorporation to Nucleic Acids.
European Journal of Organic Chemistry. Roč. 2018, č. 37 (2018), s. 5092-5108. ISSN 1434-193X. E-ISSN 1099-0690
R&D Projects: GA ČR(CZ) GA16-00178S; GA TA ČR(CZ) TE01020028; GA MŠMT(CZ) LO1304; GA MŠMT(CZ) LM2015064
Grant - others:AV ČR(CZ) AP1501
Program: Akademická prémie - Praemium Academiae
Institutional support: RVO:61388963
Keywords : nucleosides * nucleotides * fused heterocycles * cytostatics * antiviral agents
OECD category: Organic chemistry
Impact factor: 3.029, year: 2018

Two series of substituted benzo[g]- or benzo[e]pyrimido[4,5-b]indole (naphtho-fused 7-deazapurine) ribonucleosides were synthesized. The heterocyclic nucleobases were obtained by Negishi cross-coupling reaction of zincated pyrimidines with naphthyl iodides, nucleophilic substitution to tetrazoles/azides and thermal cyclization or photocyclization. Nucleosides were obtained by glycosylation followed by substitution reactions and deprotection. Resulting ribonucleosides were tested for their cytotoxic activity against cancer cell lines and antiviral activities. Some derivatives showed micromolar cytotoxic activities and moderate anti-hepatitis C virus activities. Naphtho-fused 7-deazapurine 2-deoxyribonucleoside triphosphate was successfully incorporated into DNA oligonucleotides by KOD XL DNA polymerase. Fluorescence properties of naphtho-fused 7-deazapurine nucleosides and oligonucleotides were also studied.
Permanent Link: http://hdl.handle.net/11104/0288477