Synthesis and biological profiling of 6- or 7-(het)aryl-7-deazapurine 4′-C-methylribonucleosides

Nauš, Petr; Caletková, Oľga; Perlíková, Pavla; Slavětínská, Lenka Poštová; Tloušťová, Eva; Hodek, Jan; Weber, Jan; Džubák, Petr; Hajdúch, Marián; Hocek, Michal

doi:10.1016/j.bmc.2015.10.040

Cited by 16 publications

(10 citation statements)

References 45 publications

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“…Submicromolar cytotoxicities were observed among 2′‐fluorinated analogues of 5‐iodotubercidin 16a and 16b and 7‐vinyl‐7‐deazaadenine 2′‐fluoronucleoside 17 also showed moderate (micromolar) cytotoxic activity . Introduction of 4′‐ C ‐methyl group into 7‐hetaryl‐7‐deazaadenosines led to complete loss of cytotoxic effect with the only exception of 2‐benzofuryl derivative 18 with modest (micromolar) activity . In conclusion, likewise among naturally occurring cytotoxic 7‐deazapurine nucleosides, modifications of the ribose moiety in 7‐substituted 7‐deazapurine nucleosides mostly result in significant decrease of cytotoxic activities.…”

Section: Cytotoxic Nucleosidesmentioning

confidence: 81%

“…48 Introduction of 4 ′ -C-methyl group into 7-hetaryl-7-deazaadenosines led to complete loss of cytotoxic effect with the only exception of 2-benzofuryl derivative 18 with modest (micromolar) activity. 49 In conclusion, likewise among naturally occurring cytotoxic 7-deazapurine nucleosides, modifications of the ribose moiety in 7-substituted 7-deazapurine nucleosides mostly result in significant decrease of cytotoxic activities.…”

Section: Synthetic Nucleosides With C7 and C8 Substituentsmentioning

confidence: 91%

“…Also, the ribonucleoside moiety was shown to be crucial for keeping the potency of 6-hetaryl-7-deazapurine nucleosides as all of the sugar-modified derivatives, such as 33a-33e and 34, were devoid of any cytotoxic activity. 49,75,76 ( Fig. 9).…”

Section: Synthetic Nucleosides With C6 Substituentsmentioning

confidence: 96%

“…Several fluorinated 7-deazapurine nucleosides showed activity against human immunodeficiency virus (HIV). Submicromolar anti-HIV activities and no cytotoxicity were observed for derivatives 78 143 (EC 50 = 0.5 M) and 79 49 (EC 50 = 0.71 M) indicating that this class of nucleosides might bring more interesting anti-HIV candidates in the future. Compound 80 bearing a 7-(pyridine-2-yl)vinyl group showed promising results against influenza A virus (EC 50/H1N1 strain = 5.88 M and EC 50/H3N2 strain = 6.95 M) and low toxicity (CC 50 > 100 M).…”

Section: Nucleosides With Antiviral Activities Against Other Virusesmentioning

confidence: 97%

“…Only some modest (micromolar) activity of 2‐fluoro derivative 32a was observed, more bulky 2‐chloro‐ ( 32b ), 2‐amino‐ ( 32c ), and 2‐methyl ( 32d ) derivatives were inactive. Also, the ribonucleoside moiety was shown to be crucial for keeping the potency of 6‐hetaryl‐7‐deazapurine nucleosides as all of the sugar‐modified derivatives, such as 33a ‐ 33e and 34 , were devoid of any cytotoxic activity . (Fig.…”

Section: Cytotoxic Nucleosidesmentioning

confidence: 99%

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Pyrrolo[2,3‐d]pyrimidine (7‐deazapurine) as a privileged scaffold in design of antitumor and antiviral nucleosides

Perlíková

Hocek

2017

Medicinal Research Reviews

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Abstract7‐Deazapurine (pyrrolo[2,3‐d]pyrimidine) nucleosides are important analogues of biogenic purine nucleosides with diverse biological activities. Replacement of the N7 atom with a carbon atom makes the five‐membered ring more electron rich and brings a possibility of attaching additional substituents at the C7 position. This often leads to derivatives with increased base‐pairing in DNA or RNA or better binding to enzymes. Several types of 7‐deazapurine nucleosides with potent cytostatic or cytotoxic effects have been identified. The most promising are 7‐hetaryl‐7‐deazaadenosines, which are activated in cancer cells by phosphorylation and get incorporated both to RNA (causing inhibition of proteosynthesis) and to DNA (causing DNA damage). Mechanism of action of other types of cytostatic nucleosides, 6‐hetaryl‐7‐deazapurine and thieno‐fused deazapurine ribonucleosides, is not yet known. Many 7‐deazaadenosine derivatives are potent inhibitors of adenosine kinases. Many types of sugar‐modified derivatives of 7‐deazapurine nucleosides are also strong antivirals. Most important are 2′‐C‐methylribo‐ or 2′‐C‐methyl‐2′‐fluororibonucleosides with anti‐HCV activities (several compounds underwent clinical trials). Some underexplored areas of potential interest are also outlined.

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Section: Cytotoxic Nucleosidesmentioning

confidence: 81%

Section: Synthetic Nucleosides With C7 and C8 Substituentsmentioning

confidence: 91%

Section: Synthetic Nucleosides With C6 Substituentsmentioning

confidence: 96%

Section: Nucleosides With Antiviral Activities Against Other Virusesmentioning

confidence: 97%

Section: Cytotoxic Nucleosidesmentioning

confidence: 99%

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Pyrrolo[2,3‐d]pyrimidine (7‐deazapurine) as a privileged scaffold in design of antitumor and antiviral nucleosides

Perlíková

Hocek

2017

Medicinal Research Reviews

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Covalent Modification of Nucleobases using Water‐Soluble Palladium Catalysts

Shaughnessy

2022

The Chemical Record

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Nucleosides represent one of the key building blocks of biochemistry. There is significant interest in the synthesis of nucleoside-derived materials for applications as probes, biochemical models, and pharmaceuticals. Palladium-catalyzed cross-coupling reactions are effective methods for making covalent modification of carbon and nitrogen sites on nucleobases under mild conditions. Water-soluble catalysts derived from palladium and hydrophilic ligands, such as tris(3-sulfonatophenyl)phosphine trisodium (TPPTS), are efficient catalysts for a range of coupling reactions of unprotected halonucleosides. Over the past two decades, these methods have been extended to direct functionalization of halonucleotides, as well as RNA and DNA oligonucleotides (ONs) containing halogenated bases. These methods can be run under biocompatible conditions, including examples of Suzuki coupling of modified DNA in whole cells and tissue samples. In this account, development of this methodology by our group and others is highlighted along with the extension of these catalyst systems to modification of nucleotides and ONs.

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Application of Water-Soluble Palladium-Catalyst Systems for Introduction of C C Bonds in Nucleosides

Shaughnessy

2018

Palladium-Catalyzed Modification of Nucleosides, Nucleotides and Oligonucleotides

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Synthesis and biological profiling of 6- or 7-(het)aryl-7-deazapurine 4′-C-methylribonucleosides

Cited by 16 publications

References 45 publications

Pyrrolo[2,3‐d]pyrimidine (7‐deazapurine) as a privileged scaffold in design of antitumor and antiviral nucleosides

Pyrrolo[2,3‐d]pyrimidine (7‐deazapurine) as a privileged scaffold in design of antitumor and antiviral nucleosides

Covalent Modification of Nucleobases using Water‐Soluble Palladium Catalysts

Application of Water-Soluble Palladium-Catalyst Systems for Introduction of C C Bonds in Nucleosides

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