Novel Central Nervous System (CNS)-Targeting Protease Inhibitors for Drug-Resistant HIV Infection and HIV-Associated CNS Complications-Reference-Cited by-同舟云学术

Novel Central Nervous System (CNS)-Targeting Protease Inhibitors for Drug-Resistant HIV Infection and HIV-Associated CNS Complications

Published:2019-07 Issue:7 Volume:63 Page:
ISSN:0066-4804
Container-title:Antimicrobial Agents and Chemotherapy
language:en
Short-container-title:Antimicrob Agents Chemother

Author:

Amano Masayuki¹²^ORCID,Salcedo-Gómez Pedro Miguel¹²,Yedidi Ravikiran S.³^ORCID,Zhao Rui¹²,Hayashi Hironori¹²,Hasegawa Kazuya⁴,Nakamura Tomofumi¹²,Martyr Cuthbert D.⁵⁶,Ghosh Arun K.⁵⁶,Mitsuya Hiroaki¹²³⁷^ORCID

Affiliation:

1. Department of Infectious Diseases, Kumamoto University School of Medicine, Kumamoto, Japan

2. Department of Hematology, Kumamoto University School of Medicine, Kumamoto, Japan

3. Experimental Retrovirology Section, HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

4. Protein Crystal Analysis Division, Japan Synchrotron Radiation Research Institute, Hyogo, Japan

5. Department of Chemistry, Purdue University, West Lafayette, Indiana, USA

6. Department of Medicinal Chemistry, Purdue University, West Lafayette, Indiana, USA

7. National Center for Global Health and Medicine Research Institute, Tokyo, Japan

Abstract

There is currently no specific therapeutics for the HIV-1-related central nervous system (CNS) complications. Here we report that three newly designed CNS-targeting HIV-1 protease inhibitors (PIs), GRL-083-13, GRL-084-13, and GRL-087-13, which contain a P1-3,5- bis -fluorophenyl or P1- para -monofluorophenyl ring, and P2- bis -tetrahydrofuran ( bis -THF) or P2-tetrahydropyrano-tetrahydrofuran ( Tp -THF), with a sulfonamide isostere, are highly active against wild-type HIV-1 strains and primary clinical isolates (50% effective concentration [EC 50 ], 0.0002 to ∼0.003 μM), with minimal cytotoxicity.

Funder

HHS | National Institutes of Health

Ministry of Health, Labour and Welfare

Ministry of Education, Culture, Sports, Science and Technology

National Center for Global Health and Medicine

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

Link

https://journals.asm.org/doi/pdf/10.1128/AAC.00466-19

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