Toward new therapeutics for skin and soft tissue infections: propargyl-linked antifolates are potent inhibitors of MRSA and Streptococcus pyogenes. | LitMetric
Department of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut, United States of America.
Published: July 2012
AI Article Synopsis
Article Abstract
Hospital- and community-acquired, complicated skin and soft tissue infections, often attributed to Staphylococcus aureus and Streptococcus pyogenes, present a significant health burden that is associated with increased health care costs and mortality. As these two species are difficult to discern on diagnosis and are associated with differential profiles of drug resistance, the development of an efficacious antibacterial agent that targets both organisms is a high priority. Herein we describe a structure-based drug development effort that has produced highly potent inhibitors of dihydrofolate reductase from both species. Optimized propargyl-linked antifolates containing a key pyridyl substituent display antibacterial activity against both methicillin-resistant S. aureus and S. pyogenes at MIC values below 0.1 µg/mL and minimal cytotoxicity against mammalian cells. Further evaluation against a panel of clinical isolates shows good efficacy against a range of important phenotypes such as hospital- and community-acquired strains as well as strains resistant to vancomycin.
Department of Laboratory Medicine, The Affiliated Changsha Hospital of Xiangya School of Medicine (The First Hospital of Changsha), Central South University, No. 311, Yingpan Road, Changsha, 410005, Hunan, China.
Antibiotic resistance by methicillin-resistant Staphylococcus aureus (MRSA) is an urgent threat to human health. The biofilm and persister cells formation ability of MRSA and Staphylococcus epidermidis often companied with extremely high antimicrobial resistance. Pinaverium bromide (PVB) is an antispasmodic compound mainly used for irritable bowel syndrome.
Antibiotic-resistant pathogens in public settings present a growing risk to human health. Staphylococcus aureus often asymptomatically colonizes human skin, while virulent strains cause soft tissue infections, osteomyelitis, endocarditis, and are associated with cystic fibrosis. Here we investigated the presence and distribution of multidrug-resistant S.
Background: Cysticercosis, a parasitic infection caused by the larval stages of the pork tapeworm, Taenia solium, predominantly affects cerebral and ocular tissues. The subcutaneous manifestation of this disease is a relatively uncommon clinical occurrence. Previously very few or no cases of cysticercosis presenting as subcutaneous solitary painful swelling have been reported in the literature.
The cashmere goat is a type of livestock primarily known for its cashmere. Cashmere has a soft hand feel and good luster. It is a vital raw material in the textile industry, possessing significant economic value.
is a human pathogen responsible for a variety of diseases, from skin, soft tissue, and lung infections to severe cases such as meningitis, infective endocarditis, and bacteremia. The high level of antibiotic resistance in these pathogens, exemplified by methicillin-resistant (MRSA), necessitates the development of effective antibiotics. Thus, this work introduced the chemical synthesis of ethyl 3,5-dibromoorsellinate, a derivative of ethyl orsellinate from the lichen mycobiont of , and its effectiveness against MRSA was assessed.
