Journal article
Polybiguanides, particularly polyethylene hexamethylene biguanide, have activity against human immunodeficiency virus type 1
Biomedicine & pharmacotherapy, v 59(8), pp 438-445
2005
PMID: 16154720
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Polyhexamethylene biguanide (PHMB) is a polybiguanide (PBG) oligomer with antimicrobial activity that is used extensively and safely as a disinfectant. The reported mechanism of PHMB antimicrobial activity, which involves interactions with cell membrane components, suggested that PHMB or other PBG-based compounds might also have antiviral or virucidal activity against the human immunodeficiency virus type 1 (HIV-1). PHMB had modest
in vitro activity against both cell-free and cell-associated HIV-1, as well as the ability to interfere with viral binding and entry. However, PHMB was comparable in cytotoxicity to the spermicidal agent nonoxynol-9 (N-9), a compound that has been characterized in previous studies as generally cytotoxic and detrimental to cervicovaginal epithelial integrity. To identify structural variants of PHMB with greater anti-HIV-1 activity and/or less cytotoxicity, modified versions of PHMB incorporating length changes in the hydrocarbon linker units were synthesized and evaluated for
in vitro cytotoxicity and inhibition of HIV-1 infectivity. These experiments demonstrated that the PHMB variant polyethylene hexamethylene biguanide (PEHMB) was just as active against HIV-1 as PHMB, yet was much less cytotoxic than either N-9 or PHMB, resulting in an
in vitro therapeutic index (TI) approximately 114-fold greater than the TI of N-9. PEHMB, which has been identified in these studies as a promising microbicidal candidate in this family of compounds, will be the focus of further
in vitro and
in vivo evaluations of anti-HIV-1 activity, toxicity, and mechanisms of action.
Metrics
Details
- Title
- Polybiguanides, particularly polyethylene hexamethylene biguanide, have activity against human immunodeficiency virus type 1
- Creators
- Fred C Krebs - Department of Microbiology and Immunology, and Center for Sexually Transmitted Disease, Center for Molecular Therapeutics, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129 USAShendra R Miller - Department of Microbiology and Immunology, and Center for Sexually Transmitted Disease, Center for Molecular Therapeutics, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129 USAMary Lee Ferguson - Department of Microbiology and Immunology, and Center for Sexually Transmitted Disease, Center for Molecular Therapeutics, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129 USAMohamed Labib - Novaflux Biosciences, Inc., 1 Wall Street, Princeton, NJ 08540 USARobert F Rando - Novaflux Biosciences, Inc., 1 Wall Street, Princeton, NJ 08540 USABrian Wigdahl - Department of Microbiology and Immunology, and Center for Sexually Transmitted Disease, Center for Molecular Therapeutics, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129 USA
- Publication Details
- Biomedicine & pharmacotherapy, v 59(8), pp 438-445
- Publisher
- Elsevier SAS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000232464500003
- Scopus ID
- 2-s2.0-25644439332
- Other Identifier
- 991014877705604721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Medicine, Research & Experimental
- Pharmacology & Pharmacy