Abstract
Cost and toxicity problems associated with highly active antiretroviral therapy (HAART) in HIV/AIDS treatment could be alleviated by using designed multiple ligands (DMLs). Dual inhibitors of HIV reverse transcriptase (RT) and integrase (IN) were rationally designed by introducing a diketoacid (DKA) functionality into the tolerant C-5 site of RT inhibitor delavirdine. The resulting compounds all demonstrate good activity against both RT and IN in enzymatic assays and HIV in cell-based assay, whereas their C-7 regioisomers are all inactive in these assays. Balanced activities were observed with C-3 halogenated inhibitors.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3587-3595 |
| Number of pages | 9 |
| Journal | Bioorganic and Medicinal Chemistry |
| Volume | 16 |
| Issue number | 7 |
| DOIs | |
| State | Published - Apr 1 2008 |
Bibliographical note
Funding Information:This research was supported by the Center for Drug Design at the University of Minnesota. We thank Dr. Eric Bennett for discussion, Dr. Christine Salomon for IN assay and Christine Dreis for RT assay. We also thank Roger Ptak at Southern Research Institute for cell-based assay, Dr. Robert Craigie of NIH for the integrase plasmid and Dr. William Shannon for consultation and discussion.
Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.
UN SDGs
This output contributes to the following UN Sustainable Development Goals (SDGs)
-
SDG 3 Good Health and Well-being
Keywords
- Dual inhibitors
- HIV
- Integrase
- Reverse transcriptase
Fingerprint
Dive into the research topics of 'Design and synthesis of dual inhibitors of HIV reverse transcriptase and integrase: Introducing a diketoacid functionality into delavirdine'. Together they form a unique fingerprint.Cite this
- APA
- Standard
- Harvard
- Vancouver
- Author
- BIBTEX
- RIS