Virtual Screening of Acyclovir Derivatives as Potential Antiviral Agents: Design, Synthesis, and Biological Evaluation of New Acyclic Nucleoside ProTides

Derudas, Marco; Vanpouille, Christophe; Carta, Davide; Zicari, Sonia; Andrei, Gracíela; Snoeck, Robert; Brancale, Andrea; Margolis, Leonid; Balzarini, Jan; McGuigan, Christopher

doi:10.1021/acs.jmedchem.7b01009

Cited by 14 publications

(9 citation statements)

References 23 publications

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“…While virtual screening of compounds that are active against mutant RT forms is not widely used, an application of molecular docking to virtual screening of compounds, active against wild-type of RT can be performed [ 75 , 76 , 77 , 78 , 79 , 80 , 81 ]. Typically such studies provide some insights into intermolecular interactions affecting both wild-type and mutant enzymes.…”

Section: Resultsmentioning

confidence: 99%

Molecular Docking Studies of HIV-1 Resistance to Reverse Transcriptase Inhibitors: Mini-Review

2018

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Currently, millions of people are living with human immunodeficiency virus type 1 (HIV-1), which causes acquired immunodeficiency syndrome. However, the spread of the HIV-1 resistance to antiviral agents is the major problem in the antiretroviral therapy and medical management of HIV-infected patients. HIV-1 reverse transcriptase (RT) is one of the key viral targets for HIV-1 inhibition. Therefore, the studies on the combatting the HIV resistance that occurs due to the structural changes in RT, are in great demand. This work aims to provide an overview of the state-of-the-art molecular docking approaches applied to the studies of the HIV-1 resistance, associated with RT structure changes. We have reviewed recent studies using molecular docking with mutant forms of RT. The work discusses the modifications of molecular docking, which have been developed to find the novel molecules active against resistance mutants of RT and/or recombinant strains of HIV-1. The perspectives of the existing algorithms of molecular docking to the studies on molecular mechanisms of resistance and selection of the correct binding poses for the reverse transcriptase inhibitors are discussed.

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Section: Resultsmentioning

confidence: 99%

Molecular Docking Studies of HIV-1 Resistance to Reverse Transcriptase Inhibitors: Mini-Review

2018

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“…To overcome the cytotoxicity observed with these prodrugs, very recently a virtual screening on a library of ACV derivatives was reported. 168 Docking experiments with a database of 3600 compounds against three different enzymes encompassing HIV reverse transcriptase, adenylate or guanylate kinase, and a model of DNA polymerase γ resulted in the selection of five NAs as potentially strong RT inhibitors and weak cellular DNA polymerase inhibitors including GCV, PCV, 6-Cl-PCV, 6-OMe-PCV and 2′-SH-GCV. Several phosphoramidate prodrugs of the selected NAs were synthesized and assessed for their potency against HIV, HSV, VZV, and HCMV.…”

Section: Protide Approach Application To Antiviral Nucleosidesmentioning

confidence: 99%

“…As reported before, over the last 20 years, ANPs have emerged as a novel class of clinically effective antiviral agents. 168 Explorations of various types of nucleoside phosphonate prodrugs have also led to the design and development of their aryloxyamidate prodrugs. ProTides originally designed to deliver nucleoside monophosphates, have also been successfully applied to nucleoside phosphonates.…”

Section: Protide Approach Application To Antiviral Nucleosidesmentioning

confidence: 99%

Phosphoramidates and phosphonamidates (ProTides) with antiviral activity

Ślusarczyk

Serpi

Pertusati

2018

Antivir Chem Chemother

105

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Following the first report on the nucleoside phosphoramidate (ProTide) prodrug approach in 1990 by Chris McGuigan, the extensive investigation of ProTide technology has begun in many laboratories. Designed with aim to overcome limitations and the key resistance mechanisms associated with nucleoside analogues used in the clinic (poor cellular uptake, poor conversion to the 5'-monophosphate form), the ProTide approach has been successfully applied to a vast number of nucleoside analogues with antiviral and anticancer activity. ProTides consist of a 5'-nucleoside monophosphate in which the two hydroxyl groups are masked with an amino acid ester and an aryloxy component which once in the cell is enzymatically metabolized to deliver free 5'-monophosphate, which is further transformed to the active 5'-triphosphate form of the nucleoside analogue. In this review, the seminal contribution of Chris McGuigan's research to this field is presented. His technology proved to be extremely successful in drug discovery and has led to two Food and Drug Administration-approved antiviral agents.

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“…7 Many studies have shown that purine derivatives adjacent to heteroatoms have potential drug activity, such as 9-(tetrahydrofuryl)adenine (9-THF-Ade), A 3 adenosine receptor antagonist, and antiviral active molecule (Scheme 1b). 8…”

Section: Introductionmentioning

confidence: 99%

Cross dehydrogenation coupling reaction of purine derivatives with thioethers

2022

Org. Biomol. Chem.

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Virtual Screening of Acyclovir Derivatives as Potential Antiviral Agents: Design, Synthesis, and Biological Evaluation of New Acyclic Nucleoside ProTides

Cited by 14 publications

References 23 publications

Molecular Docking Studies of HIV-1 Resistance to Reverse Transcriptase Inhibitors: Mini-Review

Molecular Docking Studies of HIV-1 Resistance to Reverse Transcriptase Inhibitors: Mini-Review

Phosphoramidates and phosphonamidates (ProTides) with antiviral activity

Cross dehydrogenation coupling reaction of purine derivatives with thioethers

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