Antiviral Activities of 9- R -2-Phosphonomethoxypropyl Adenine (PMPA) and Bis(isopropyloxymethylcarbonyl)PMPA against Various Drug-Resistant Human Immunodeficiency Virus Strains-Reference-Cited by-同舟云学术

Antiviral Activities of 9- R -2-Phosphonomethoxypropyl Adenine (PMPA) and Bis(isopropyloxymethylcarbonyl)PMPA against Various Drug-Resistant Human Immunodeficiency Virus Strains

Published:1998-06 Issue:6 Volume:42 Page:1484-1487
ISSN:0066-4804
Container-title:Antimicrobial Agents and Chemotherapy
language:en
Short-container-title:Antimicrob Agents Chemother

Author:

Srinivas Ranga V.¹,Fridland Arnold¹²

Affiliation:

1. Department of Infectious Diseases, St. Jude Children’s Research Hospital,1 and

2. Department of Pharmacology, University of Tennessee,2 Memphis, Tennessee

Abstract

ABSTRACT 9- R -2-Phosphonomethoxypropyl adenine (PMPA) is an acyclic nucleoside phosphonate analog that has demonstrated efficacy against human immunodeficiency virus (HIV). We recently described the synthesis, metabolism, and biological activities of bis(isopropyloxymethylcarbonyl)PMPA [bis(poc)PMPA] as an orally bioavailable prodrug for PMPA. Among a large panel of drug-resistant HIV type 1 variants, only the K65R virus was resistant to PMPA. K65R virus also showed reduced susceptibility to bis(poc)PMPA, although the prodrug could still inhibit these viruses at submicromolar, nontoxic concentrations. Among a panel of seven primary clinical isolates from patients with diverse treatment histories, only one isolate showed reduced susceptibility to PMPA and was found to carry three mutations (M41L, T69N, R73K) in its reverse transcriptase catalytic domain.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

Link

https://journals.asm.org/doi/pdf/10.1128/AAC.42.6.1484

Reference41 articles.

1. Synthesis, in vitro evaluation and oral bioavailability of [9-(2-phosphonylmethoxyethyl)adenine prodrugs.;Armilli M. N.;Antivir. Chem. Chemother.,1997

2. Balzarini J. De Clercq E. Acyclic purine nucleoside phosphonates as retrovirus inhibitors Antiviral chemotherapy. Jeffries D. J. De Clercq E. 1995 41 45 John Wiley & Sons Inc. New York N.Y

3. Bischofberger N. Naesens L. De Clercq E. Fridland A. Srinivas R. V. Robbins B. L. Arimilli M. Cundy K. Kim C. Lacy S. Lee W. Shaw J. Bis(POC)PMPA an orally bioavailable prodrug of the antiretroviral agent PMPA abstr. 214 Program and abstracts of the 4th Conference on Retroviruses and Opportunistic Infections 1997 104

4. Antiretroviral therapy for HIV infection in 1997. Updated recommendations of the International AIDS Society-USA Panel.;Carpenter C. C.;JAMA,1997

5. Cherrington J. M. Van Rompay K. K. A. Multao A. S. Marthas M. L. Berardi C. J. Telm S. Bischofberger N. Pedersen N. C. Phenotypic and genotypic characterization of simian immunodeficiency viruses (SIV) with reduced susceptibility to PMPA isolated after PMPA therapy abstr. 75. Program and abstracts of Fifth International Workshop on HIV Drug Resistance 1996

Cited by 91 articles. 订阅此论文施引文献订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献

1. Improved pharmacokinetics of tenofovir ester prodrugs strengthened the inhibition of HBV replication and the rebalance of hepatocellular metabolism in preclinical models;Frontiers in Pharmacology;2022-08-29

2. Phosphonates and Phosphonate Prodrugs in Medicinal Chemistry: Past Successes and Future Prospects;Frontiers in Chemistry;2022-05-20

3. Design, synthesis and antiviral evaluation of novel acyclic phosphonate nucleotide analogs with triazolo[4,5-b]pyridine, imidazo[4,5-b]pyridine and imidazo[4,5-b]pyridin-2(3H)-one systems;Nucleosides, Nucleotides & Nucleic Acids;2019-09-25

4. Rational Development of Liposomal Hydrogels: A Strategy for Topical Vaginal Antiretroviral Drug Delivery in the Context of HIV Prevention;Pharmaceutics;2019-09-18

5. Development and in vivo safety assessment of tenofovir-loaded nanoparticles-in-film as a novel vaginal microbicide delivery system;Acta Biomaterialia;2016-10