Design, synthesis, and in vitro biological evaluation of novel 6-methyl-7-substituted-7-deaza purine nucleoside analogs as anti-influenza A agents

Lin, Cai; Sun, Chenghai; Liu, Xiao; Zhou, Yiqian; Hussain, Muzammal; Wan, Junting; Li, Minke; Li, Xue; Jin, Ruiliang; Tu, Zhengchao; Zhang, Jiancun

doi:10.1016/j.antiviral.2016.01.005

Cited by 23 publications

(15 citation statements)

References 26 publications

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“…During more recent years, 2ʹ‐substituted carba‐nucleoside analogues , C‐3ʹ‐modified analogues , and 6‐methyl‐7‐substituted‐7‐deaza purine nucleoside analogues were reported to have anti‐influenza activity comparable to 2ʹ‐FdG. The antiviral activity of 2ʹ‐FdG and analogues is dependent on intracellular conversion to the active nucleoside 5ʹ‐triphosphate form.…”

Section: Strategies To Interfere With the Influenza Virus Polymerasementioning

confidence: 99%

“…161 The identity of the amino acid changes in this mutant polymerase was not disclosed, which is unfortunate since this insight could be very helpful to explain the role of specific residues in the catalytic or other functional domain of PB1, as identified in the recent crystallographic studies. 23,24,56,58 During more recent years, 2ʹ-substituted carba-nucleoside analogues, 100 C-3ʹ-modified analogues, 102 and 6-methyl-7-substituted-7-deaza purine nucleoside analogues 103 were reported to have anti-influenza activity comparable to 2ʹ-FdG. The antiviral activity of 2ʹ-FdG and analogues is dependent on intracellular conversion to the active nucleoside 5ʹ-triphosphate form.…”

Section: ʹ-Deoxy-2ʹ-fluoroguanosine and Other Nucleoside Analoguesmentioning

confidence: 99%

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The Influenza Virus Polymerase Complex: An Update on Its Structure, Functions, and Significance for Antiviral Drug Design

Stevaert

Naesens

2016

Medicinal Research Reviews

136

151

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Influenza viruses cause seasonal epidemics and pandemic outbreaks associated with significant morbidity and mortality, and a huge cost. Since resistance to the existing anti‐influenza drugs is rising, innovative inhibitors with a different mode of action are urgently needed. The influenza polymerase complex is widely recognized as a key drug target, given its critical role in virus replication and high degree of conservation among influenza A (of human or zoonotic origin) and B viruses. We here review the major progress that has been made in recent years in unravelling the structure and functions of this protein complex, enabling structure‐aided drug design toward the core regions of the PA endonuclease, PB1 polymerase, or cap‐binding PB2 subunit. Alternatively, inhibitors may target a protein–protein interaction site, a cellular factor involved in viral RNA synthesis, the viral RNA itself, or the nucleoprotein component of the viral ribonucleoprotein. The latest advances made for these diverse pharmacological targets have yielded agents in advanced (i.e., favipiravir and VX‐787) or early clinical testing, besides several experimental inhibitors in various stages of development, which are all covered here.

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Section: Strategies To Interfere With the Influenza Virus Polymerasementioning

confidence: 99%

Section: ʹ-Deoxy-2ʹ-fluoroguanosine and Other Nucleoside Analoguesmentioning

confidence: 99%

The Influenza Virus Polymerase Complex: An Update on Its Structure, Functions, and Significance for Antiviral Drug Design

Stevaert

Naesens

2016

Medicinal Research Reviews

136

151

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“…Submicromolar anti‐HIV activities and no cytotoxicity were observed for derivatives 78 (EC 50 = 0.5 μM) and 79 (EC 50 = 0.71 μM) 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 μM and EC 50/H3N2 strain = 6.95 μM) and low toxicity (CC 50 > 100 μM) . This derivative could serve as a basis for further lead optimization studies with an aim of developing novel anti‐influenza A virus agents.…”

Section: Nucleosides With Antiviral Activitiesmentioning

confidence: 97%

“…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: 98%

“…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). 143 This derivative could serve as a basis for further lead optimization studies with an aim of developing novel anti-influenza A virus agents.…”

Section: Nucleosides With Antiviral Activities Against Other Virusesmentioning

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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Recent Efforts in Identification of Privileged Scaffolds as Antiviral Agents

Yadav,

Singh,

Sharma

et al. 2023

Chemistry & Biodiversity

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Viral infections are the most important health concern nowdays to mankind, which is unexpectedly increasing the health complications and fatality rate worldwide. The recent viral infection outbreak develops a pressing need for small molecules that can be quickly deployed for the control/treatment of re‐emerging or new emerging viral infections. Numerous viruses, including the human immunodeficiency virus (HIV), hepatitis, influenza, SARS‐CoV‐1, SARS‐CoV‐2, and others are still challanging due to emerging resistant to known drugs. Therefore, there is alway a need to search for new antiviral small molecules who can combat viral infection with new mode of action. This review highlighted rececnt progress on development of new antiviral molecule based on natural product inspired scafflods. Herein, structure activity relationship of the FDA approved drugs alongwith the molecular docking studies of selected compounds have been discussed against several target proteins. The findings of new small molecules as neuraminidase inhibtors, other than known drug scafflods, Anti‐HIV and SARS‐CoV are incorporated in this review paper.

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Design, synthesis, and in vitro biological evaluation of novel 6-methyl-7-substituted-7-deaza purine nucleoside analogs as anti-influenza A agents

Cited by 23 publications

References 26 publications

The Influenza Virus Polymerase Complex: An Update on Its Structure, Functions, and Significance for Antiviral Drug Design

The Influenza Virus Polymerase Complex: An Update on Its Structure, Functions, and Significance for Antiviral Drug Design

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

Recent Efforts in Identification of Privileged Scaffolds as Antiviral Agents

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