This report describes the evaluation of N-thiolated beta-lactam antibiotics as potential anti-Bacillus agents. N-Thiolated beta-lactams are a new family of antibacterials that previously have been found to selectively inhibit the growth of Staphylococcus bacteria over many other genera of microbes. From the data presented herein, these lactams similarly inhibit a variety of Bacillus species, including Bacillus anthracis. The preliminary structure-activity studies suggest that there is a need to balance the lipophilic character of the C3/C4 groups in order to obtain optimal anti-Bacillus activity. Elongation or extensive branching of the organothio substituent diminishes antibacterial effects, with the sec-butylthio derivative providing the strongest activity.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bmcl.2006.01.070 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The impact of fatty acids on the antibacterial properties of N-thiolated β-lactams.
Bioorg Med Chem Lett
September 2011
Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, FL, USA.
Bacterial fatty acid synthesis (FAS) is a potentially important, albeit controversial, target for antimicrobial therapy. Recent studies have suggested that the addition of exogenous fatty acids (FAs) to growth media can circumvent the effects of FAS-targeting compounds on bacterial growth. Consequently, such agents may have limited in vivo applicability for the treatment of human disease, as free FAs are abundant within the body.
View Article and Find Full Text PDFPhysical properties and biological activity of poly(butyl acrylate-styrene) nanoparticle emulsions prepared with conventional and polymerizable surfactants.
Nanomedicine
December 2009
Center for Molecular Diversity in Drug Design, Discovery, and Delivery, Department of Chemistry, University of South Florida, Tampa, Florida, USA.
Unlabelled: Recent efforts in our laboratory have explored the use of polyacrylate nanoparticles in aqueous media as stable emulsions for potential applications in treating drug-resistant bacterial infections. These emulsions are made by emulsion polymerization of acrylated antibiotic compounds in a mixture of butyl acrylate and styrene (7:3 wt/wt) using sodium dodecyl sulfate as a surfactant. Prior work in our group established that the emulsions required purification to remove toxicity associated with extraneous surfactant present in the media.
View Article and Find Full Text PDFStudies on the antifungal properties of N-thiolated beta-lactams.
Bioorg Med Chem
August 2008
Center for Molecular Diversity in Drug Design, Discovery, and Delivery, Department of Chemistry, 4202 East Fowler Avenue, CHE 205, University of South Florida, Tampa, FL 33620, USA.
N-thiolated beta-lactams had previously been shown to have antibacterial activity against a narrow selection of pathogenic bacteria including Staphylococcus aureus and Bacillus anthracis, as well as apoptotic-inducing activity in a variety of human cancer cell lines. We now have found that these lactams also possess antifungal activity against Candida and other fungi by exerting powerful cytostatic effects that disrupt the structural integrity of cytoplasmic membranes. The mode of action and structure-activity trends of these lactams as antifungals parallel that previously seen in our antibacterial studies.
View Article and Find Full Text PDFUnsymmetric aryl-alkyl disulfide growth inhibitors of methicillin-resistant Staphylococcus aureus and Bacillus anthracis.
Bioorg Med Chem
July 2008
Center for Molecular Diversity in Drug Design, Discovery, and Delivery, Department of Chemistry, 4202 East Fowler Avenue, CHE 205, University of South Florida, Tampa, FL 33620, USA.
This study describes the antibacterial properties of synthetically produced mixed aryl-alkyl disulfide compounds as a means to control the growth of Staphylococcus aureus and Bacillus anthracis. Some of these compounds exerted strong in vitro bioactivity. Our results indicate that among the 12 different aryl substituents examined, nitrophenyl derivatives provide the strongest antibiotic activities.
View Article and Find Full Text PDFInduction of tumor cell apoptosis by a novel class of N-thiolated beta-lactam antibiotics with structural modifications at N1 and C3 of the lactam ring.
Int J Mol Med
June 2008
The Prevention Program, Barbara Ann Karmanos Cancer Institute, and Department of Pathology, School of Medicine, Wayne State University, Detroit, MI 48201, USA.
The investigation of novel anti-tumor agents that preferentially select for malignant cells with a tolerable toxicity level has been the focus of anti-cancer drug discovery. Our laboratories have previously reported that certain N-alkylthiolated beta-lactams had DNA-damaging and apoptosis-inducing activity in various tumor lines but not in nontransformed cells. In the current study, we further delineated the effects of substitutions at C3 or N1 of the lactam ring for cell death-inducing capability with close attention paid to a discernible structure-activity relationship (SAR).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!