Design and synthesis of dual inhibitors of HIV reverse transcriptase and integrase: Introducing a diketoacid functionality into delavirdine

Zhengqiang Wang; Robert Vince

doi:10.1016/j.bmc.2008.02.007

Design and synthesis of dual inhibitors of HIV reverse transcriptase and integrase: Introducing a diketoacid functionality into delavirdine

Zhengqiang Wang, Robert Vince

Research output: Contribution to journal › Article › peer-review

52 Scopus citations

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	https://doi.org/10.1016/j.bmc.2008.02.007
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.

Keywords

Dual inhibitors
HIV
Integrase
Reverse transcriptase

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bmc.2008.02.007

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title = "Design and synthesis of dual inhibitors of HIV reverse transcriptase and integrase: Introducing a diketoacid functionality into delavirdine",

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.",

keywords = "Dual inhibitors, HIV, Integrase, Reverse transcriptase",

author = "Zhengqiang Wang and Robert Vince",

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.",

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doi = "10.1016/j.bmc.2008.02.007",

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AU - Vince, Robert

N1 - 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.

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AB - 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.

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KW - HIV

KW - Integrase

KW - Reverse transcriptase

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Design and synthesis of dual inhibitors of HIV reverse transcriptase and integrase: Introducing a diketoacid functionality into delavirdine

Abstract

Bibliographical note

Keywords

UN SDGs

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