Synthesis of Acyclic Selenonucleoside Phosphonates as Potential Antiviral Agents

Sahu, Pramod K.; Kim, Gyudong; Nayak, Akshata; Ahn, Ji Yoon; Ha, Min Woo; Park, Cheonhyoung; Yu, Jinha; Park, Hyeung‐geun; Jeong, Lak Shin

doi:10.1002/ajoc.201500421

Cited by 9 publications

(3 citation statements)

References 14 publications

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“…There is a growing body of evidence that resistance to antiviral drugs has become a major ongoing clinical issue. Besides, the discovery of novel molecules to treat viral infections has attracted considerable attention due to the high prevalence of these diseases, the appearance of new viral strains and re-emergence of some viruses, and the limited treatments available. − It is worth mentioning that a plethora of research is dedicated toward the synthesis of novel Se derivatives of a wide range of antivirals and the study of their pharmacological activities. − …”

Section: Selenized Small Molecule Drugsmentioning

confidence: 99%

Selenization of Small Molecule Drugs: A New Player on the Board

Morán-Serradilla,

Plano,

Sanmartín

et al. 2024

J. Med. Chem.

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There is an urgent need to develop safer and more effective modalities for the treatment of a wide range of pathologies due to the increasing rates of drug resistance, undesired side effects, poor clinical outcomes, etc. Throughout the years, selenium (Se) has attracted a great deal of attention due to its important role in human health. Besides, a growing body of work has unveiled that the inclusion of Se motifs into a great number of molecules is a promising strategy for obtaining novel therapeutic agents. In the current Perspective, we have gathered the most recent literature related to the incorporation of different Se moieties into the scaffolds of a wide range of known drugs and their feasible pharmaceutical applications. In addition, we highlight different representative examples as well as provide our perspective on Se drugs and the possible future directions, promises, opportunities, and challenges of this ground-breaking area of research. ■ SIGNIFICANCE • Significance: The development of novel compounds for the treatment of numerous pathologies has become a priority due to the lack of effective therapeutic options. • Impact: This work highlights the potential of incorporating Se moieties into the scaffold of several drugs to develop novel safer bioactive compounds. • Innovation: This Perspective discusses the development of selenoderivatives of a wide array of drugs and their biological applications and proposes novel avenues to continue exploring this outstanding research area.

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Section: Selenized Small Molecule Drugsmentioning

confidence: 99%

Selenization of Small Molecule Drugs: A New Player on the Board

Morán-Serradilla,

Plano,

Sanmartín

et al. 2024

J. Med. Chem.

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“…Selenium was also introduced in the sugar moieties of various nucleoside derivatives and in the acyclic chain of antiviral acyclic compounds. − For example, selenium analogs of acyclovir and ganciclovir exhibited potent activity against herpes simplex virus and human cytomegalovirus . Recently, increased attention was focused on the photophysics of 6-selanylguanine, which is necessary for the further structural study of DNA/RNA duplexes containing aforementioned nucleobases. − …”

Section: Introductionmentioning

confidence: 99%

Synthesis of 6-Selanyl-2-triazolylpurine Derivatives Using 2,6-Bistriazolylpurines as Starting Materials

Ritere,

Jeminejs,

Bizde̅na

et al. 2024

ACS Omega

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Two pathways toward 6-selanyl-2-triazolylpurine derivatives were designed. The first method involved the synthesis of 2-chloro-6-selanylpurine derivatives, further S N Ar reaction with NaN 3 , and following CuAAC using different alkynes. The second method was based on the synthesis of 2,6-bistriazolylpurine derivatives as starting materials followed by S N Ar reaction with commercial or in situ generated selenols as nucleophiles. A series of 2-chloro-6-selanylpurine derivatives were obtained in yields up to 84%. It was found that in the latter compounds, 6-selanyl moiety was the better leaving group compared to 2-chlorosubstituent in S N Ar reactions. On the other hand, the S N Ar reaction between 2,6-bistriazolylpurines and selenols or diselenides was successful, and 13 examples of 6-selanyl-2-triazolylpurine derivatives were obtained in yields up to 87%. This direct approach for the Se−C bond formation proved the ability of the 1,2,3-triazolyl ring at the C6 position of purine to act as a good leaving group.

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“…[1][2][3] Notably, this technique has been applied for the investigation of ribozymes, [4] riboswitches, [5] homo-DNA, [6] and for HIV-1 drug discovery. [7] Besides their application in X-ray crystallography, selenium-modified nucleic acids are potential therapeutics for the treatment of cancer, [8,9] as well as viral [10][11][12] or bacterial infections. [13] In addition, they have attracted interest as diagnostic agents.…”

Section: Introductionmentioning

confidence: 99%

Optimized Biocatalytic Synthesis of 2‐Selenopyrimidine Nucleosides by Transglycosylation**

et al. 2021

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Selenium‐modified nucleosides are powerful tools to study the structure and function of nucleic acids and their protein interactions. The widespread application of 2‐selenopyrimidine nucleosides is currently limited by low yields in established synthetic routes. Herein, we describe the optimization of the synthesis of 2‐Se‐uridine and 2‐Se‐thymidine derivatives by thermostable nucleoside phosphorylases in transglycosylation reactions using natural uridine or thymidine as sugar donors. Reactions were performed at 60 or 80 °C and at pH 9 under hypoxic conditions to improve the solubility and stability of the 2‐Se‐nucleobases in aqueous media. To optimize the conversion, the reaction equilibria in analytical transglycosylation reactions were studied. The equilibrium constants of phosphorolysis of the 2‐Se‐pyrimidines were between 5 and 10, and therefore differ by an order of magnitude from the equilibrium constants of any other known case. Hence, the thermodynamic properties of the target nucleosides are inherently unfavorable, and this complicates their synthesis significantly. A tenfold excess of sugar donor was needed to achieve 40−48 % conversion to the target nucleoside. Scale‐up of the optimized conditions provided four Se‐containing nucleosides in 6–40 % isolated yield, which compares favorably to established chemical routes.

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Synthesis of Acyclic Selenonucleoside Phosphonates as Potential Antiviral Agents

Cited by 9 publications

References 14 publications

Selenization of Small Molecule Drugs: A New Player on the Board

Selenization of Small Molecule Drugs: A New Player on the Board

Synthesis of 6-Selanyl-2-triazolylpurine Derivatives Using 2,6-Bistriazolylpurines as Starting Materials

Optimized Biocatalytic Synthesis of 2‐Selenopyrimidine Nucleosides by Transglycosylation**

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