Polymers Fight HIV: Potent (Pro)Drugs Identified Through Parallel Automated Synthesis

Zuwała, Kaja; Smith, Anders; Postma, Almar; Guerrero‐Sánchez, Carlos; Ruiz-Sanchis, Pau; Melchjorsen, Jesper; Tolstrup, Martin; Zelikin, Alexander N.

doi:10.1002/adhm.201400148

Cited by 18 publications

(23 citation statements)

References 31 publications

(28 reference statements)

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“…Against HIV, the polymers were employed to prevent infectivity of the replication-competent HIV-1 in TZM-bl cells using luciferase expression as a read-out 17 (Fig. 2C).…”

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confidence: 99%

Macromolecular prodrugs of ribavirin: towards a treatment for co-infection with HIV and HCV

et al. 2015

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“…Against HIV, the polymers were employed to prevent infectivity of the replication-competent HIV-1 in TZM-bl cells using luciferase expression as a read-out 17 (Fig. 2C).…”

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confidence: 99%

Macromolecular prodrugs of ribavirin: towards a treatment for co-infection with HIV and HCV

et al. 2015

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“…Zuwala et al [ 51 ], have also utilized acrylate derivatives in synthesizing two polymers. The group synthesized conjugates with poly(methacrylic acid) (PMAA) and HPMA ( 14 and 15 in Figure 8 , respectively), and claimed that the PMAA-AZT conjugate resulted in a longer duration of action when compared to the pristine drug.…”

Section: Macromolecular Prodrugsmentioning

confidence: 99%

Advanced Prodrug Strategies in Nucleoside and Non-Nucleoside Antiviral Agents: A Review of the Recent Five Years

2017

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Background: Poor pharmacokinetic profiles and resistance are the main two drawbacks from which currently used antiviral agents suffer, thus make them excellent targets for research, especially in the presence of viral pandemics such as HIV and hepatitis C. Methods: The strategies employed in the studies covered in this review were sorted by the type of drug synthesized into ester prodrugs, targeted delivery prodrugs, macromolecular prodrugs, other nucleoside conjugates, and non-nucleoside drugs. Results: Utilizing the ester prodrug approach a novel isopropyl ester prodrug was found to be potent HIV integrase inhibitor. Further, employing the targeted delivery prodrug zanamivir and valine ester prodrug was made and shown a sole delivery of zanamivir. Additionally, VivaGel, a dendrimer macromolecular prodrug, was found to be very efficient and is now undergoing clinical trials. Conclusions: Of all the strategies employed (ester, targeted delivery, macromolecular, protides and nucleoside analogues, and non-nucleoside analogues prodrugs), the most promising are nucleoside analogues and macromolecular prodrugs. The macromolecular prodrug VivaGel works by two mechanisms: envelope mediated and receptor mediated disruption. Nucleotide analogues have witnessed productive era in the recent past few years. The era of non-interferon based treatment of hepatitis (through direct inhibitors of NS5A) has dawned.

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“…The PMAA-AZT polymer conjugates thereby offer a combination therapeutic whereby the drug and polymer inhibit HIV infectivity through different mechanisms. [116] Another example of a reverse transcriptase inhibitor that has been conjugated to a polymer is stavudine (Figure 4), which has been conjugated to chitosan. [117] In comparison to stavudine loaded chitosan nanoparticles, the chitosan phosphoester conjugated stavudine showed lower but sustained drug release rates at pH 1.1 (simulated gastric juice) and pH 7.4 (extracellular fluids).…”

Section: Polymer-reverse Transcriptase Inhibitor Conjugatesmentioning

confidence: 99%

“…In contrast, copolymers consisting of 2‐hydroxypropyl‐methacrylamide (HPMA) and AZT side chain modified methacrylate did not exhibit any dual activity. The PMAA‐AZT polymer conjugates thereby offer a combination therapeutic whereby the drug and polymer inhibit HIV infectivity through different mechanisms . Another example of a reverse transcriptase inhibitor that has been conjugated to a polymer is stavudine (Figure ), which has been conjugated to chitosan .…”

Section: Polymeric Anti‐hiv Therapeuticsmentioning

confidence: 99%

Polymeric Anti‐HIV Therapeutics

Danial

Klok

2014

Macromolecular Bioscience

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The scope of this review is to highlight the application of polymer therapeutics in an effort to curb the transmission and infection of the human immunodeficiency virus (HIV). Following a description of the HIV life cycle, the use of approved antiretroviral drugs that inhibit critical steps in the HIV infection process is highlighted. After that, a comprehensive overview of the structure and inhibitory properties of polymeric anti‐HIV therapeutic agents is presented. This overview will include inhibitors based on polysaccharides, synthetic polymers, dendritic polymers, polymer conjugates as well as polymeric DC‐SIGN antagonists. The review will conclude with a section that discusses the applications of polymers and polymer conjugates as systemic and topical anti‐HIV therapeutics.

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Polymers Fight HIV: Potent (Pro)Drugs Identified Through Parallel Automated Synthesis

Cited by 18 publications

References 31 publications

Macromolecular prodrugs of ribavirin: towards a treatment for co-infection with HIV and HCV

Macromolecular prodrugs of ribavirin: towards a treatment for co-infection with HIV and HCV

Advanced Prodrug Strategies in Nucleoside and Non-Nucleoside Antiviral Agents: A Review of the Recent Five Years

Polymeric Anti‐HIV Therapeutics

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