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Richard W. Scott  - - - 
Top co-authors See all
William F. DeGrado

32 shared publications

University of California, San Francisco

Gill Diamond

14 shared publications

Department of Oral Biology, Rutgers New Jersey Dental School, Newark, NJ 07103, USA

Dahui Liu

12 shared publications

PolyMedix, Inc., Radnor, Pennsylvania 19087, United States

Lisa Kathleen Ryan

3 shared publications

The Public Health Research Institute Center, Rutgers New Jersey Medical School, Newark, NJ 07103, USA

Jeffrey C. Pelletier

2 shared publications

Fox Chase Chemical Diversity Center, Inc., 3805 Old Easton Road, Doylestown, Pennsylvania 18902, United States

7
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61
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Publication Record
Distribution of Articles published per year 
(2006 - 2018)
Total number of journals
published in
 
7
 
Publications See all
Article 1 Read 0 Citations Antifungal Potential of Host Defense Peptide Mimetics in a Mouse Model of Disseminated Candidiasis Mobaswar Hossain Chowdhury, Lisa Kathleen Ryan, Kartikeya Ch... Published: 27 February 2018
Journal of Fungi, doi: 10.3390/jof4010030
DOI See at publisher website ABS Show/hide abstract
Invasive candidiasis caused by Candida albicans and non-albicans Candida (NAC) present a serious disease threat. Although the echinocandins are recommended as the first line of antifungal drug class, resistance to these agents is beginning to emerge, demonstrating the need for new antifungal agents. Host defense peptides (HDP) exhibit potent antifungal activity, but as drugs they are difficult to manufacture efficiently, and they are often inactivated by serum proteins. HDP mimetics are low molecular weight non-peptide compounds that can alleviate these problems and were shown to be membrane-active against C. albicans and NAC. Here, we expand upon our previous works to describe the in vitro and in vivo activity of 11 new HDP mimetics that are active against C. albicans and NAC that are both sensitive and resistant to standard antifungal drugs. These compounds exhibit minimum inhibitory/fungicidal concentration (MIC/MFC) in the µg/mL range in the presence of serum and are inhibited by divalent cations. Rapid propidium iodide influx into the yeast cells following in vitro exposure suggested that these HDP mimetics were also membrane active. The lead compounds were able to kill C. albicans in an invasive candidiasis CD-1 mouse model with some mimetic candidates decreasing kidney burden by 3–4 logs after 24 h in a dose-dependent manner. The data encouraged further development of this new anti-fungal drug class for invasive candidiasis.
Article 0 Reads 2 Citations Potent in vitro and in vivo antifungal activity of a small molecule host defense peptide mimic through a membrane-active... Lorenzo P. Menzel, Hossain Mobaswar Chowdhury, Jorge Adrian ... Published: 28 June 2017
Scientific Reports, doi: 10.1038/s41598-017-04462-6
DOI See at publisher website PubMed View at PubMed ABS Show/hide abstract
Lethal systemic fungal infections of Candida species are increasingly common, especially in immune compromised patients. By in vitro screening of small molecule mimics of naturally occurring host defense peptides (HDP), we have identified several active antifungal molecules, which also exhibited potent activity in two mouse models of oral candidiasis. Here we show that one such compound, C4, exhibits a mechanism of action that is similar to the parent HDP upon which it was designed. Specifically, its initial interaction with the anionic microbial membrane is electrostatic, as its fungicidal activity is inhibited by cations. We observed rapid membrane permeabilization to propidium iodide and ATP efflux in response to C4. Unlike the antifungal peptide histatin 5, it did not require energy-dependent transport across the membrane. Rapid membrane disruption was observed by both fluorescence and electron microscopy. The compound was highly active in vitro against numerous fluconazole-resistant clinical isolates of C. albicans and non-albicans species, and it exhibited potent, dose-dependent activity in a mouse model of invasive candidiasis, reducing kidney burden by three logs after 24 hours, and preventing mortality for up to 17 days. Together the results support the development of this class of antifungal drug to treat invasive candidiasis.
Article 0 Reads 1 Citation Mimics of Host Defense Proteins; Strategies for Translation to Therapeutic Applications. Richard W Scott, Gregory N Tew Published: 13 July 2016
Current Topics in Medicinal Chemistry,
PubMed View at PubMed
Article 0 Reads 3 Citations Acinetobacter baumannii OxPhos inhibitors as selective anti-infective agents Harvey Rubin, Trevor Selwood, Takahiro Yano, Damian G. Weave... Published: 01 January 2015
Bioorganic & Medicinal Chemistry Letters, doi: 10.1016/j.bmcl.2014.11.020
DOI See at publisher website PubMed View at PubMed
Article 0 Reads 7 Citations Activity of Potent and Selective Host Defense Peptide Mimetics in Mouse Models of Oral Candidiasis Lisa K. Ryan, Katie B. Freeman, Jorge A. Masso-Silva, Klaudi... Published: 21 April 2014
Antimicrobial Agents and Chemotherapy, doi: 10.1128/AAC.02649-13
DOI See at publisher website PubMed View at PubMed
Article 0 Reads 20 Citations De Novo Design of Self-Assembling Foldamers That Inhibit Heparin–Protein Interactions Geronda L. Montalvo, Yao Zhang, Trevor M. Young, Michael J. ... Published: 11 February 2014
ACS Chemical Biology, doi: 10.1021/cb500026x
DOI See at publisher website PubMed View at PubMed
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