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These superior, highly potent N-Arylated NH125 analogues demonstrate broad-spectrum antibacterial activities against even drug-resistant strains and are promising agents for disinfectants and antiseptics that eradicate bacteria, biofilms and persister cells. Biofilms are pervasive, surface-attached colonies of bacteria or other microorganisms that form a protective extracellular matrix, making them difficult to kill. Biofilms with dormant persister cells are highly tolerant of antibiotics and biocides. Persister cells of methicillin-resistant Staphylococcus aureus (MRSA) play a major role in the 100,000 serious infections and 18,000 deaths yearly, with treatments resulting in $4 billion in costs in the United States alone.
Researchers at the University of Florida have developed powerful N-arylated NH125 analogues that have proven to be potent and rapid in killing MRSA persister cells in stationary cultures when compared to a panel of membrane-targeting antimicrobial peptides, including quaternary ammonium cations.
N-arylated NH125 analogues act as potent antibacterial agents, biofilm eradicators, and MRSA persister cell killers
Researchers at the University of Florida have modified the arrangement of the anti-bacterial compound, NH125, into two distinct N-Arylated analogues that kill MRSA persister cells and other resistant bacteria. Similar to NH125, the analogues have a long aliphatic tail and an imidazole heterocycle that contains a charged nitrogen atom. This arrangement enables the chemical to rupture the bacterial membranes, killing them. Additionally, the NH125 structure has an N-arylated-2-methylimidazole heterocycle which is augmented in the analogues to contain an additional functional group. This allows the chemical agents to better target bacterial or fungal cells. When tested against MRSA, methicillin-resistant Staphylococcus epidermis (MRSE), and vancomycin-resistant Enterococcus faecium (VRE), the analogues outperformed all other membrane-targeting antibacterial agents.
This molecular antagonist has been shown to prevent morphine-seeking behavior in animals and may be an effective treatment for opioid addiction in humans . The Center for Disease Control and Prevention estimates that opioid prescription misuse accounts for $78.5 billion in economic burden, and in 2019 alone, nearly 50,000 people died from opioid overdoses. , Medication-assisted treatment is effective in helping combat opioid addiction. However, only a handful of medications are available to treat opioid addiction, and more effective treatments are needed to help address the opioid crisis.
Researchers at the University of Florida have developed a small complex molecule that may be an effective treatment for opioid addiction. This molecule is part of a larger chemical library that contains architecturally diverse molecules that may also be useful as anticancer, antibacterial, and antimalarial drug candidates.
Small complex molecule that is an antagonist for the receptor associated with opioid addiction and may be an effective opioid addiction treatment
Medication-assisted treatment is an effective method for combating opioid addiction, but only a few drugs are available for use. This molecular antagonist binds to the HCRTR2 receptor and may be an effective treatment for opioid addiction. This molecule is part of a larger library of chemical architectures derived from the indole alkaloid, Vincamine. Other molecules in the library may be anticancer, antibacterial, and antimalarial drug candidates.
This series of antibacterial agents, known as the halogenated phenazines, are able to eradicate free-floating (planktonic) bacteria in addition to persistent, surface-attached bacterial biofilms against gram positive organisms such as methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE) and vancomycin-resistant Enterococcus faecium (VRE). Bacterial cells housed within a biofilm are metabolically dormant, persister cells that display high levels of tolerance towards conventional antibiotics and biocides. Bacterial biofilms occur in the majority of bacterial infections and accumulate on essentially all surface types, including medical implants and industrial pipes. Researchers at the University of Florida have discovered halogenated phenazine small molecules that are able to eradicate greater than 99.9 percent of biofilm cells through a mechanism that is non-toxic to mammalian cell lines, including red blood cells. In addition, select halogenated phenazine analogues have potent antibacterial activities against the slow-growing human pathogen Mycobacterium tuberculosis.
Clinical and non-clinical applications for eradicating biofilm-associated bacterial pathogens and surfaces colonized by persistent biofilms.
The halogenated phenazine scaffold is highly tunable, which has been demonstrated through the synthesis and evaluation of more than 80 synthetic analogues. Continued efforts are underway to further develop halogenated phenazines for numerous applications related to bacterial biofilm infections and disinfectants. These halogenated phenazines have demonstrated the most potent biofilm eradication activities reported in the literature against MRSA, MRSE and VRE biofilms. In addition to biofilms, select halogenated phenazine analogues demonstrate potent antibacterial activity against M. tuberculosis.
