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International Journal of Molecular... Dec 2022Purine nucleosides represent an interesting group of nitrogen heterocycles, showing a wide range of biological effects. In this study, we designed and synthesized a...
Purine nucleosides represent an interesting group of nitrogen heterocycles, showing a wide range of biological effects. In this study, we designed and synthesized a series of 6,9-disubstituted and 2,6,9-trisubstituted purine ribonucleosides via consecutive nucleophilic aromatic substitution, glycosylation, and deprotection of the ribofuranose unit. We prepared eight new purine nucleosides bearing unique adamantylated aromatic amines at position 6. Additionally, the ability of the synthesized purine nucleosides to form stable host-guest complexes with β-cyclodextrin (β-CD) was confirmed using nuclear magnetic resonance (NMR) and mass spectrometry (ESI-MS) experiments. The in vitro antiproliferative activity of purine nucleosides and their equimolar mixtures with β-CD was tested against two types of human tumor cell line. Six adamantane-based purine nucleosides showed an antiproliferative activity in the micromolar range. Moreover, their effect was only slightly suppressed by the presence of β-CD, which was probably due to the competitive binding of the corresponding purine nucleoside inside the β-CD cavity.
Topics: Humans; Adamantane; Purine Nucleosides; beta-Cyclodextrins; Cell Line, Tumor; Nucleosides
PubMed: 36499470
DOI: 10.3390/ijms232315143 -
Molecules (Basel, Switzerland) Mar 2015Transition metal-catalyzed modifications of the activated heterocyclic bases of nucleosides as well as DNA or RNA fragments employing traditional cross-coupling methods... (Review)
Review
Transition metal-catalyzed modifications of the activated heterocyclic bases of nucleosides as well as DNA or RNA fragments employing traditional cross-coupling methods have been well-established in nucleic acid chemistry. This review covers advances in the area of cross-coupling reactions in which nucleosides are functionalized via direct activation of the C8-H bond in purine and the C5-H or C6-H bond in uracil bases. The review focuses on Pd/Cu-catalyzed couplings between unactivated nucleoside bases with aryl halides. It also discusses cross-dehydrogenative arylations and alkenylations as well as other reactions used for modification of nucleoside bases that avoid the use of organometallic precursors and involve direct C-H bond activation in at least one substrate. The scope and efficiency of these coupling reactions along with some mechanistic considerations are discussed.
Topics: Carbon; Catalysis; Hydrogen; Purine Nucleosides; Pyrimidine Nucleosides
PubMed: 25789821
DOI: 10.3390/molecules20034874 -
Annals of the New York Academy of... 1990
Review
Topics: Adenosine; Adenosine Triphosphate; Animals; Central Nervous System; Neurotransmitter Agents; Purine Nucleosides; Purine Nucleotides; Receptors, Purinergic
PubMed: 1981308
DOI: 10.1111/j.1749-6632.1990.tb37664.x -
Current Pharmaceutical Design 2002The synthesis and the pharmacological activity of alkynyl derivatives of adenosine (Ado) and N-ethylcarboxamidoadenosine (NECA), that have been tested on adenosine... (Review)
Review
The synthesis and the pharmacological activity of alkynyl derivatives of adenosine (Ado) and N-ethylcarboxamidoadenosine (NECA), that have been tested on adenosine receptors from different sources, have been reviewed. Most of compounds have been characterized in the last ten years by using radioligand binding assays on rat brain membranes and functional studies on different animal models. More recently, the four human adenosine receptor subtypes have been stably transfected into Chinese hamster ovary (CHO) cells allowing for comparative studies in a similar cellular background, utilizing radioligand binding studies (A(1), A(2A), A(3)) or adenylate cyclase activity assays (A(2B)). From the whole pattern of studies the following structure-activity relationships have been drown: The activities of 2-alkynylAdos resulted slightly higher at A(1) and lower at A(3) and A(2B) subtypes than the corresponding NECA derivatives, whereas the affinities at A(2A) subtype are similar for the two series of nucleosides. The presence of a methyl group on N(6) of the 2-alkynyladenosines, inducing a contemporary increase in affinity at the human A(3) receptor and a decrease at the other subtypes, resulted in a relevant increase in A(3) selectivity. In particular, 2-phenylethynyl-N(6)-methylAdo showed an A(3) affinity in the low nanomolar range (K(i) A(3) = 3.4 nM), and about 500 fold A(1)/A(3) and about 2500 fold A(2A)/A(3) selectivity. The presence of a hydroxyl group in some alkynyl side chains led to potent inhibitors of platelet aggegation induced by ADP. -Introduction of particular substituents, such as the racemic 2-phenylhydroxypropynyl group, both in adenosine and in NECA analogues, led to highly potent, non selective agonists at all the four subtypes. For the potency at A(2B) receptor it seems to be very important the type of alkynyl chain in 2-position and the presence of the carboxyamido group on the sugar; in fact, the (S)-2-phenylhydroxypropynylNECA [(S)-PHPNECA, EC(50) A(2B) = 220 nM] proved to be one of the most potent A(2B) agonist reported so far. The introduction of alkynyl chain in 8-position of adenosine led to very selective ligands for the A(3) receptor subtype. These nucleosides behave as adenosine antagonists, since they do not stimulate basal [(35)S]GTPgammaS binding, but inhibit NECA-stimulated binding.
Topics: Animals; Humans; Purine Nucleosides; Purinergic P1 Receptor Agonists; Receptors, Purinergic P1
PubMed: 12369946
DOI: 10.2174/1381612023392856 -
Chemical Communications (Cambridge,... Aug 2015C-H bond functionalisation of heteroarenes, especially nucleosides, has received a lot of attention in the past few years. This review describes the state-of the art in... (Review)
Review
C-H bond functionalisation of heteroarenes, especially nucleosides, has received a lot of attention in the past few years. This review describes the state-of the art in this area with a global aspiration for possibly functionalising purine and pyrimidine moieties in more complex biomolecular systems, such as DNA/RNA in the near future.'
Topics: Carbon; Catalysis; Chemistry Techniques, Synthetic; DNA; Purine Nucleosides; Pyrimidine Nucleosides; RNA
PubMed: 26050746
DOI: 10.1039/c5cc03416g -
Biochemical Pharmacology Jun 1980
Review
Topics: Adenosine; Animals; Electric Stimulation; Humans; Neuroeffector Junction; Neurons; Purine Nucleosides; Purine Nucleotides; Purines; Synaptic Transmission
PubMed: 6250541
DOI: 10.1016/0006-2952(80)90117-3 -
Nature Jun 2020The nature of the first genetic polymer is the subject of major debate. Although the 'RNA world' theory suggests that RNA was the first replicable information carrier of...
The nature of the first genetic polymer is the subject of major debate. Although the 'RNA world' theory suggests that RNA was the first replicable information carrier of the prebiotic era-that is, prior to the dawn of life-other evidence implies that life may have started with a heterogeneous nucleic acid genetic system that included both RNA and DNA. Such a theory streamlines the eventual 'genetic takeover' of homogeneous DNA from RNA as the principal information-storage molecule, but requires a selective abiotic synthesis of both RNA and DNA building blocks in the same local primordial geochemical scenario. Here we demonstrate a high-yielding, completely stereo-, regio- and furanosyl-selective prebiotic synthesis of the purine deoxyribonucleosides: deoxyadenosine and deoxyinosine. Our synthesis uses key intermediates in the prebiotic synthesis of the canonical pyrimidine ribonucleosides (cytidine and uridine), and we show that, once generated, the pyrimidines persist throughout the synthesis of the purine deoxyribonucleosides, leading to a mixture of deoxyadenosine, deoxyinosine, cytidine and uridine. These results support the notion that purine deoxyribonucleosides and pyrimidine ribonucleosides may have coexisted before the emergence of life.
Topics: Adenosine; Cytidine; DNA; Evolution, Chemical; Origin of Life; Oxidation-Reduction; Purine Nucleosides; Pyrimidine Nucleosides; RNA; Uridine
PubMed: 32494078
DOI: 10.1038/s41586-020-2330-9 -
Advances in Enzyme Regulation
Review
Topics: Adenosine Deaminase; Antineoplastic Agents; Phosphotransferases; Purine Nucleosides; Purine-Nucleoside Phosphorylase; Thioinosine; Vidarabine
PubMed: 211817
DOI: 10.1016/0065-2571(78)90077-8 -
The Journal of Physical Chemistry. B Oct 2018The chemical difference between DNA and RNA nucleosides is their 2'-hydrogen versus 2'-hydroxyl substituents. Modification of the ribosyl moiety at the 2'-position and...
The chemical difference between DNA and RNA nucleosides is their 2'-hydrogen versus 2'-hydroxyl substituents. Modification of the ribosyl moiety at the 2'-position and 2'-O-methylation in particular, is common among natural post-transcriptional modifications of RNA. 2'-Modification may alter the electronic properties and hydrogen-bonding characteristics of the nucleoside and thus may lead to enhanced stabilization or malfunction. The structures and relative glycosidic bond stabilities of the protonated forms of the 2'-O-methylated purine nucleosides, 2'-O-methyladenosine (Adom) and 2'-O-methylguanosine (Guom), were examined using two complementary tandem mass spectrometry approaches, infrared multiple photon dissociation action spectroscopy and energy-resolved collision-induced dissociation. Theoretical calculations were also performed to predict the structures and relative stabilities of stable low-energy conformations of the protonated forms of the 2'-O-methylated purine nucleosides and their infrared spectra in the gas phase. Low-energy conformations highly parallel to those found for the protonated forms of the canonical DNA and RNA purine nucleosides are also found for the protonated 2'-O-methylated purine nucleosides. Importantly, the preferred site of protonation, nucleobase orientation, and sugar puckering are preserved among the DNA, RNA, and 2'-O-methylated variants of the protonated purine nucleosides. The 2'-substituent does however influence hydrogen-bond stabilization as the 2'-O-methyl and 2'-hydroxyl substituents enable a hydrogen-bonding interaction between the 2'- and 3'-substituents, whereas a 2'-hydrogen atom does not. Further, 2'-O-methylation reduces the number of stable low-energy hydrogen-bonded conformations possible and importantly inverts the preferred polarity of this interaction versus that of the RNA analogues. Trends in the CID values extracted from survival yield analyses of the 2'-O-methylated and canonical DNA and RNA forms of the protonated purine nucleosides are employed to elucidate their relative glycosidic bond stabilities. The glycosidic bond stability of Adom is found to exceed that of its DNA and RNA analogues. The glycosidic bond stability of Guom is also found to exceed that of its DNA analogue; however, this modification weakens this bond relative to its RNA counterpart. The glycosidic bond stability of the protonated purine nucleosides appears to be correlated with the hydrogen-bond stabilization of the sugar moiety.
Topics: Adenosine; Guanosine; Methylation; Models, Molecular; Molecular Conformation; Ribose; Tandem Mass Spectrometry; Thermodynamics
PubMed: 30203656
DOI: 10.1021/acs.jpcb.8b07687 -
Organic Letters Jun 2003[reaction: see text] The title compound, a constitutional isomer of the natural nucleobase 2,6-diaminopurine, undergoes regioselective electrophilic substitutions at...
[reaction: see text] The title compound, a constitutional isomer of the natural nucleobase 2,6-diaminopurine, undergoes regioselective electrophilic substitutions at carbon C-9.
Topics: 2-Aminopurine; Aza Compounds; Crystallography, X-Ray; Purine Nucleosides; Purines; Spectrophotometry, Ultraviolet
PubMed: 12790530
DOI: 10.1021/ol030044n