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Drug Discovery Today Jun 2021In recent years, many studies have shown that adenosine has efficacy for treating cancer. More importantly, some adenosine analogs have been successfully marketed to... (Review)
Review
In recent years, many studies have shown that adenosine has efficacy for treating cancer. More importantly, some adenosine analogs have been successfully marketed to fulfill anticancer purposes. In this review, we summarize the anticancer effects of adenosine and its analogs in clinical trials and preclinical studies, with focus on their anticancer mechanisms. In addition, we link the anticancer activities of adenosine analogs with their structures through structure-activity relationship (SAR) analysis, and highlight additional promising anticancer drug candidates. We hope that this review will be of help in understanding the importance of adenosine and its analogs with anticancer activities and directing future research and development of such compounds.
Topics: Adenosine; Animals; Antineoplastic Agents; Drug Development; Humans; Neoplasms; Structure-Activity Relationship
PubMed: 33639248
DOI: 10.1016/j.drudis.2021.02.020 -
Current Protocols in Nucleic Acid... Jun 20206-Methylpurine (MeP) is a cytotoxic adenine analog that does not exhibit selectivity when administered systemically and could be very useful in a gene therapy approach...
6-Methylpurine (MeP) is a cytotoxic adenine analog that does not exhibit selectivity when administered systemically and could be very useful in a gene therapy approach to cancer treatment involving Escherichia coli purine nucleoside phosphorylase (PNP). 9-(6-Deoxy-β-D-allofuranosyl)-6-methylpurine [methyl(allo)-MePR, 18] and 9-(6-deoxy-α-L-talofuranosyl)-6-methylpurine [methyl(talo)-MePR, 21] were synthesized as potential prodrugs for MeP in the E. coli PNP/prodrug cancer gene therapy approach. The detailed syntheses of [methyl(allo)-MePR] and [methyl(talo)-MePR] are described. The glycosyl donors, 1,2-di-O-acetyl-3,5-di-O-benzyl-α-D-allofuranose (12) and 1-O-acetyl-3-O-benzyl-2,5-di-O-benzoyl-α-L-talofuranose (16) were prepared from 1,2:5,6-di-O-isopropylidene-α-D-glucofuranose (4) in nine and eleven steps, respectively. Vorbrüggen coupling of the latter glycosyl donors with 6-methylpurine (3), followed by deprotection of the sugar hydroxyl groups, gave the title compounds in good overall yields. © 2020 by John Wiley & Sons, Inc. Basic Protocol 1: Preparation of 6-methylpurine Basic Protocol 2: Preparation of the D-allofuranose derivative (12) Basic Protocol 3: Preparation of 6-deoxy-α-L-talofuranoside Basic Protocol 4: Preparation of methyl(allo)-MePR (18) Basic Protocol 5: Preparation of methyl(talo)-MePR (21).
Topics: Chromatography, Thin Layer; Mass Spectrometry; Proton Magnetic Resonance Spectroscopy; Purine Nucleosides; Structure-Activity Relationship
PubMed: 32255553
DOI: 10.1002/cpnc.105 -
Trends in Genetics : TIG Nov 2022A recent study by Hu et al. describes N-methyladenosine (mA)-selective allyl chemical labeling and sequencing (mA-SAC-seq), which allows for quantitative,...
A recent study by Hu et al. describes N-methyladenosine (mA)-selective allyl chemical labeling and sequencing (mA-SAC-seq), which allows for quantitative, stoichiometric, and positional analyses of mA at single-nucleotide resolution across the whole transcriptome level. Information on the mA stoichiometry will provide additional layers of gene regulatory pathways mediated by mA modification during diverse molecular, cellular, and physiological events.
Topics: Adenosine; Nucleotides; Transcriptome
PubMed: 35792016
DOI: 10.1016/j.tig.2022.06.009 -
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 -
Biochemical and Biophysical Research... Oct 2023Hematological malignancies(HMs) are highly heterogeneous diseases with globally rising incidence. Despite major improvements in the management of HMs, conventional... (Review)
Review
Hematological malignancies(HMs) are highly heterogeneous diseases with globally rising incidence. Despite major improvements in the management of HMs, conventional therapies have limited efficacy, and relapses with high mortality rates are still frequent. Cordycepin, a nucleoside analog extracted from Cordyceps species, represents a wide range of therapeutic effects, including anti-inflammatory, anti-tumor, and anti-metastatic activities. Cordycepin induces apoptosis in different subtypes of HMs by triggering adenosine receptors, death receptors, and several vital signaling pathways such as MAPK, ERK, PI3K, AKT, and GSK-3β/β-catenin. This review article summarizes the impact of utilizing cordycepin on HMs, and highlights its potential as a promising avenue for future cancer research based on evidence from in vitro and in vivo studies, as well as clinical trials.
Topics: Humans; Glycogen Synthase Kinase 3 beta; Hematologic Neoplasms; Deoxyadenosines; Apoptosis
PubMed: 37634411
DOI: 10.1016/j.bbrc.2023.08.014 -
Purinergic Signalling Jun 2022Quorum sensing indicates a communication process between bacteria based on a coordinate variation in gene expression aimed at coordinating a collective comportment...
Quorum sensing indicates a communication process between bacteria based on a coordinate variation in gene expression aimed at coordinating a collective comportment related to the bacterial population density. Increasing pieces of evidence pointed out that a quorum-sensing system can be a regulatory program also used in the immune field to organize the density of the various immune cell populations and to calibrate their responses. In particular, such equilibrium is achieved by the ability of immune cells to perceive the density of their own populations or those of other cells in their environment, through the release of several mediators able to finely shape the cell density via coordinated changes in gene expression and protein signaling. In this regard, adenosine displays the typical characteristics of a mediator involved in the regulation of quorum sensing, thus suggesting a putative role of this nucleoside in shaping the balance between diverse immune cell populations.
Topics: Adenosine; Quorum Sensing; Signal Transduction
PubMed: 35501535
DOI: 10.1007/s11302-022-09866-2 -
Cancer Gene Therapy Jun 2024RNA modification, especially N6-methyladenosine, 5-methylcytosine, and N7-methylguanosine methylation, participates in the occurrence and progression of cancer through... (Review)
Review
RNA modification, especially N6-methyladenosine, 5-methylcytosine, and N7-methylguanosine methylation, participates in the occurrence and progression of cancer through multiple pathways. The function and expression of these epigenetic regulators have gradually become a hot topic in cancer research. Mutation and regulation of noncoding RNA, especially lncRNA, play a major role in cancer. Generally, lncRNAs exert tumor-suppressive or oncogenic functions and its dysregulation can promote tumor occurrence and metastasis. In this review, we summarize N6-methyladenosine, 5-methylcytosine, and N7-methylguanosine modifications in lncRNAs. Furthermore, we discuss the relationship between epigenetic RNA modification and lncRNA interaction and cancer progression in various cancers. Therefore, this review gives a comprehensive understanding of the mechanisms by which RNA modification affects the progression of various cancers by regulating lncRNAs, which may shed new light on cancer research and provide new insights into cancer therapy.
Topics: Humans; Neoplasms; RNA, Long Noncoding; Epigenesis, Genetic; Gene Expression Regulation, Neoplastic; Adenosine; Animals; RNA Processing, Post-Transcriptional
PubMed: 38351139
DOI: 10.1038/s41417-024-00734-2 -
International Journal of Molecular... May 2022Epitranscriptomic modifications can affect every aspect of RNA biology, including stability, transport, splicing, and translation, participate in global intracellular... (Review)
Review
Epitranscriptomic modifications can affect every aspect of RNA biology, including stability, transport, splicing, and translation, participate in global intracellular mRNA metabolism, and regulate gene expression and a variety of biological processes. N6-methyladenosine (m6A) as the most prevalent modification contributes to normal embryonic brain development and memory formation. However, changes in the level of m6A modification and the expression of its related proteins cause abnormal nervous system functions, including brain tissue development retardation, axon regeneration disorders, memory changes, and neural stem cell renewal and differentiation disorders. Recent studies have revealed that m6A modification and its related proteins play key roles in the development of various neuropsychiatric disorders, such as depression, Alzheimer's disease, and Parkinson's disease. In this review, we summarize the research progresses of the m6A modification regulation mechanism in the central nervous system and discuss the effects of gene expression regulation mediated by m6A modification on the biological functions of the neuropsychiatric disorders, thereby providing some insight into new research targets and treatment directions for human diseases.
Topics: Adenosine; Axons; Humans; Nerve Regeneration; RNA
PubMed: 35682599
DOI: 10.3390/ijms23115922 -
Medicinal Chemistry (Shariqah (United... 2023A new family of purine nucleoside cholinesterase inhibitors was disclosed by us, with potency and selectivity over acetylcholinesterase or butyrylcholinesterase...
BACKGROUND
A new family of purine nucleoside cholinesterase inhibitors was disclosed by us, with potency and selectivity over acetylcholinesterase or butyrylcholinesterase controlled by tuning structural and stereochemical features of nucleosides with perbenzylated glycosyl moieties.
OBJECTIVE
Design, synthesis, and biological evaluation of new purine nucleosides were used to investigate glycon protecting group pattern required for anticholinesterase activity and selectivity.
METHODS
Regioselective chemistry to introduce methyl/benzyl groups in glycon donors and Nglycosylation was used to acquire the target nucleosides. Evaluation of their biological potential and selectivity as cholinesterase inhibitors was performed.
RESULTS
Synthetic strategies chosen resulted in high glycon donor's overall yield and regio- and stereoselectivity was found in N-glycosylation reaction. Some of the new nucleosides are cholinesterase inhibitors and selectivity for butyrylcholinesterase was also achieved.
CONCLUSION
N-glycosylation reaction was stereoselective for the β-anomers while regioselectivity was achieved for the N isomers when glycon positions 2 and 3 were methylated. Cholinesterase inhibition was found when the 2,3-di-O-benzyl-4-O-methyl pattern is present in the sugar moiety. Amongst the new compounds, the two most promising ones showed micromolar inhibition (mixed inhibition), being one of them selective for butyrylcholinesterase inhibition.
Topics: Cholinesterase Inhibitors; Butyrylcholinesterase; Purine Nucleosides; Acetylcholinesterase; Nucleosides; Structure-Activity Relationship
PubMed: 35638283
DOI: 10.2174/1871520622666220527150712 -
Methods in Molecular Biology (Clifton,... 2021The conversion of adenosine to inosine (A to I) by RNA editing represents a common posttranscriptional mechanism for diversification of both the transcriptome and...
The conversion of adenosine to inosine (A to I) by RNA editing represents a common posttranscriptional mechanism for diversification of both the transcriptome and proteome, and is a part of the cellular response for innate immune tolerance. Due to its preferential base-pairing with cytosine (C), inosine (I) is recognized as guanosine (G) by reverse transcriptase, as well as the cellular splicing and translation machinery. A-to-I editing events appear as A-G discrepancies between genomic DNA and cDNA sequences. Molecular analyses of RNA editing have leveraged these nucleoside differences to quantify RNA editing in ensemble populations of RNA transcripts and within individual cDNAs using high-throughput sequencing or Sanger sequencing-derived analysis of electropherogram peak heights. Here, we briefly review and compare these methods of RNA editing quantification, as well as provide experimental protocols by which such analyses may be achieved.
Topics: Adenosine; DNA, Complementary; Genome, Human; High-Throughput Nucleotide Sequencing; Humans; Inosine; RNA Editing; Transcriptome
PubMed: 32729077
DOI: 10.1007/978-1-0716-0787-9_7