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Journal article
Novel Imino Sugar Derivatives Demonstrate Potent Antiviral Activity against Flaviviruses
Antimicrobial agents and chemotherapy, v 53(4), pp 1501-1508
Apr 2009
PMID: 19223639
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Imino sugars, such as N-butyl-deoxynojirimycin and N-nonyl-deoxynojirimycin (NNDNJ), are glucose analogues that selectively inhibit cellular α-glucosidase I and II in the endoplasmic reticulum and exhibit antiviral activities against many types of enveloped viruses. Although these molecules have broad-spectrum antiviral activity, their development has been limited by a lack of efficacy and/or selectivity. We have previously reported that a DNJ derivative with a hydroxylated cyclohexyl side chain, called OSL-95II, has an antiviral efficacy similar to that of NNDNJ but significantly less toxicity. Building upon this observation, a family of imino sugar derivatives containing an oxygenated side chain and terminally restricted ring structures were synthesized and shown to have low cytotoxicity and superior antiviral activity against members of the Flaviviridae family, including bovine viral diarrhea virus, dengue virus (DENV), and West Nile virus. Of particular interest is that several of these novel imino sugar derivatives, such as PBDNJ0801, PBDNJ0803, and PBDNJ0804, potently inhibit DENV infection in vitro, with 90% effective concentration values at submicromolar concentrations and selectivity indices greater than 800. Therefore, these compounds represent the best in their class and may offer realistic candidates for the development of antiviral therapeutics against human DENV infections.
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Details
- Title
- Novel Imino Sugar Derivatives Demonstrate Potent Antiviral Activity against Flaviviruses
- Creators
- Jinhong Chang - Drexel UniversityLijuan Wang - Drexel UniversityDongling Ma - Drexel UniversityXiaowang Qu - Drexel UniversityHaitao Guo - Drexel UniversityXiaodong Xu - Hepatitis B FoundationPeter M Mason - The University of Texas Medical Branch at GalvestonNigel Bourne - The University of Texas Medical Branch at GalvestonRobert Moriarty - University of Illinois at ChicagoBaohua Gu - Drexel UniversityJu-Tao Guo - Drexel UniversityTimothy M Block - Drexel University
- Publication Details
- Antimicrobial agents and chemotherapy, v 53(4), pp 1501-1508
- Publisher
- American Society for Microbiology
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000264356000028
- Scopus ID
- 2-s2.0-65649146500
- Other Identifier
- 991019168222304721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Microbiology
- Pharmacology & Pharmacy