Synthesis and anti-proliferative activity of 3′-deoxy-3′-fluoro-3′- C -hydroxymethyl-pyrimidine and purine nucleosides

Bhuma, Naresh; Burade, Sachin S.; Bagade, Aditi V.; Kumbhar, Navanath; Kodam, Kisan M.; Dhavale, Dilip D.

doi:10.1016/j.tet.2017.09.006

Cited by 8 publications

(6 citation statements)

References 33 publications

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“…12. 6-(4-Fluorophenyl)-N9-(2 0 ,3 0 ,5 0 -tri-O-acetyl-3 0 -C-ethynylb-D-ribofuranosyl)-purine(12) 12 was prepared according to General procedure A. 7 (0.22 g, 0.5 mmol) gave rise to 12 (0.075 g, 0.152 mmol) as a slightly yellow foam in 30% yield.…”

mentioning

confidence: 99%

Synthesis of a 3′-C-ethynyl-β-d-ribofuranose purine nucleoside library: Discovery of C7-deazapurine analogs as potent antiproliferative nucleosides

Hulpia

Noppen

Schols

et al. 2018

European Journal of Medicinal Chemistry

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A focused nucleoside library was constructed around a 3'-C-ethynyl-d-ribofuranose sugar scaffold, which was coupled to variously modified purine nucleobases. The resulting nucleosides were probed for their ability to inhibit tumor cell proliferation, as well as for their activity against a panel of relevant human viruses. While C6-aryl substituted purine nucleosides were found to be weakly active, several C7-substituted 7-deazapurine nucleosides elicited potent antiproliferative activity. Their activity spectrum was evaluated in the NCI-60 tumor cell line panel indicating activity against several solid tumor derived cell lines. Analog 32, equipped with a 7-deaza 7-chloro-6-amino-purin-9-yl base was evaluated in a metastatic breast tumor (MDA-MB-231-LM2) xenograft model. It inhibited both tumor growth and reduced the formation of lung metastases as revealed by BLI analysis. The dideazanucleoside analog 66 showed interesting activity against hCMV. These results highlight the potential advantages of recombining known sugar and nucleobase motifs as a library design strategy to discover novel antiviral or antitumor agents.

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confidence: 99%

Synthesis of a 3′-C-ethynyl-β-d-ribofuranose purine nucleoside library: Discovery of C7-deazapurine analogs as potent antiproliferative nucleosides

Hulpia

Noppen

Schols

et al. 2018

European Journal of Medicinal Chemistry

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“…Hydrolysis of compound 191 followed by acetylation led to compound 192 and this on condensation with different suitable protected nucleobases provide desired compounds 193 – 196 after deprotection (Scheme 16). These were tested for their antiproliferative activity against MDA‐MB‐231, L‐132, HeLa, neural cell lines and found to be moderately active [40] …”

Section: Sugar Fragment Modified Analoguesmentioning

confidence: 99%

“…These were tested for their antiproliferative activity against MDA-MB-231, L-132, HeLa, neural cell lines and found to be moderately active. [40] A new synthetic route to the synthesis of 2'-deoxy- ). These compounds did not show any biological activities.…”

Section: R E V I E W T H E C H E M I C a L R E C O R Dmentioning

confidence: 99%

Fluorinated Nucleosides: Synthesis, Modulation in Conformation and Therapeutic Application

Pal

Chandra

Patel

et al. 2022

The Chemical Record

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Over the last twenty years, fluorination on nucleoside has established itself as the most promising tool to use to get biologically active compounds that could sustain the clinical trial by affecting the pharmacodynamics and pharmacokinetic properties. Due to fluorine's inherent unique properties and its judicious introduction into the molecule, makes the corresponding nucleoside metabolically very stable, lipophilic, and opens a new site of intermolecular binding. Fluorination on various nucleosides has been extensively studied as a result, a series of fluorinated nucleosides come up for different therapeutic uses which are either approved by the FDA or under the advanced stage of the clinical trial. Here in this review, we are summarizing the latest development in the chemistry of fluorination on nucleoside that led to varieties of new analogs like carbocyclic, acyclic, and conformationally biased nucleoside and their biological properties, the influence of fluorine on conformation, oligonucleotide stability, and their use in therapeutics.

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“…The molecular structure generation and optimization calculations were carried out with the help of Spartan’14 (Wavefunction, Inc.) software . Similar computational studies have been performed for structural elucidations of fluorinated nucleosides and fluorinated furanoid sugar amino acids and for understanding the mechanism of transmembrane ion transport. − A total of 10 different conformer complexes were obtained, out of which the stable complex of PVD–NTO possessing the lowest energy (−2928.25 kJ/mol) was subjected for full geometry optimization by the ab initio Hartree–Fock (6-31G** basis set) method using Gaussian 16 software . The optimized complex of PVD–NTO was analyzed for intramolecular as well as intermolecular hydrogen-bonding interactions.…”

Section: Experimental Sectionmentioning

confidence: 99%

NTO Sensing by Fluorescence Quenching of a Pyoverdine Siderophore—A Mechanistic Approach

et al. 2020

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In this study, a siderophore, pyoverdine (PVD), has been isolated from Pseudomonas sp. and used to develop a fluorescence quenching-based sensor for efficient detection of nitrotriazolone (NTO) in aqueous media, in contrast to other explosives such as research department explosive (RDX), picric acid, and trinitrotoulene (TNT). The siderophore PVD exhibited enhanced fluorescence quenching above 50% at 470 nm for a minimal concentration (38 nM) of NTO. The limit of detection estimated from interpolating the graph of fluorescence intensity (at 470 nm) versus NTO concentration is found to be 12 nM corresponding to 18% quenching. The time delay fluorescence spectroscopy of the PVD–NTO solution showed a negligible change of 0.09 ns between the minimum and maximum NTO concentrations. The in silico absorption at the emission peak of static fluorescence remains invariant upon the addition of NTO. The computational studies revealed the formation of inter- and intramolecular hydrogen-bonding interactions between the energetically stable complexes of PVD and NTO. Although the analysis of Stern–Volmer plots and computational studies imply that the quenching mechanism is a combination of both dynamic and static quenching, the latter is dominant over the earlier. The static quenching is attributed to ground-state complex formation, as supported by the computational analysis.

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Synthesis and anti-proliferative activity of 3′-deoxy-3′-fluoro-3′- C -hydroxymethyl-pyrimidine and purine nucleosides

Cited by 8 publications

References 33 publications

Synthesis of a 3′-C-ethynyl-β-d-ribofuranose purine nucleoside library: Discovery of C7-deazapurine analogs as potent antiproliferative nucleosides

Synthesis of a 3′-C-ethynyl-β-d-ribofuranose purine nucleoside library: Discovery of C7-deazapurine analogs as potent antiproliferative nucleosides

Fluorinated Nucleosides: Synthesis, Modulation in Conformation and Therapeutic Application

NTO Sensing by Fluorescence Quenching of a Pyoverdine Siderophore—A Mechanistic Approach

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