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1. Development of 4-[4-(Anilinomethyl)-3-phenyl-pyrazol-1-yl] Benzoic Acid Derivatives as Potent Anti-Staphylococci and Anti-Enterococci Agents

   https://doi.org/10.3390/antibiotics11070939  

   Raj KC, Hansa; Gilmore, David F.; Alam, Mohammad A. (July 2022, Antibiotics)

   From a library of compounds, 11 hit antibacterial agents have been identified as potent anti-Gram-positive bacterial agents. These pyrazole derivatives are active against two groups of pathogens, staphylococci and enterococci, with minimum inhibitory concentration (MIC) values as low as 0.78 μg/mL. These potent compounds showed bactericidal action, and some were effective at inhibiting and eradicating Staphylococcus aureus and Enterococcus faecalis biofilms. Real-time biofilm inhibition by the potent compounds was studied, by using Bioscreen C. These lead compounds were also very potent against S. aureus persisters as compared to controls, gentamycin and vancomycin. In multiple passage studies, bacteria developed little resistance to these compounds (no more than 2 × MIC). The plausible mode of action of the lead compounds is the permeabilization of the cell membrane determined by flow cytometry and protein leakage assays. With the detailed antimicrobial studies, both in planktonic and biofilm contexts, some of these potent compounds have the potential for further antimicrobial drug development. 

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2. Efficacy of Plant-Derived Fungicides at Inhibiting Batrachochytrium salamandrivorans Growth

   https://doi.org/10.3390/jof8101025  

   Tompros, Adrianna; Wilber, Mark Q.; Fenton, Andy; Carter, Edward Davis; Gray, Matthew J. (October 2022, Journal of Fungi)

   The emerging fungal amphibian pathogen, Batrachochytrium salamandrivorans (Bsal), is currently spreading across Europe and given its estimated invasion potential, has the capacity to decimate salamander populations worldwide. Fungicides are a promising in situ management strategy for Bsal due to their ability to treat the environment and infected individuals. However, antifungal drugs or pesticides could adversely affect the environment and non-target hosts, thus identifying safe, effective candidate fungicides for in situ treatment is needed. Here, we estimated the inhibitory fungicidal efficacy of five plant-derived fungicides (thymol, curcumin, allicin, 6-gingerol, and Pond Pimafix®) and one chemical fungicide (Virkon® Aquatic) against Bsal zoospores in vitro. We used a broth microdilution method in 48-well plates to test the efficacy of six concentrations per fungicide on Bsal zoospore viability. Following plate incubation, we performed cell viability assays and agar plate growth trials to estimate the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of each fungicide. All six fungicides exhibited inhibitory and fungicidal effects against Bsal growth, with estimated MIC concentrations ranging from 60 to 0.156 μg/mL for the different compounds. Allicin showed the greatest efficacy (i.e., lowest MIC and MFC) against Bsal zoospores followed by curcumin, Pond Pimafix®, thymol, 6-gingerol, and Virkon® Aquatic, respectively. Our results provide evidence that plant-derived fungicides are effective at inhibiting and killing Bsal zoospores in vitro and may be useful for in situ treatment. Additional studies are needed to estimate the efficacy of these fungicides at inactivating Bsal in the environment and treating Bsal-infected amphibians. 

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3. In Vivo Targeting of Escherichia coli with Vancomycin-Arginine

   https://doi.org/10.1128/AAC.02416-20  

   Neville, Lewis F.; Shalit, Itamar; Warn, Peter A.; Scheetz, Marc H.; Sun, Jiuzhi; Chosy, Madeline B.; Wender, Paul A.; Cegelski, Lynette; Rendell, Jacob T. (March 2021, Antimicrobial Agents and Chemotherapy)

   null (Ed.)

   ABSTRACT The ability of vancomycin-arginine (V-r) to extend the spectrum of activity of glycopeptides to Gram-negative bacteria was investigated. Its MIC towards Escherichia coli , including β-lactamase expressing Ambler classes A, B, and D, was 8 to 16 μg/ml. Addition of 8 times the MIC of V-r to E. coli was acutely bactericidal and associated with a low frequency of resistance (<2.32 × 10 −10 ). In vivo , V-r markedly reduced E. coli burden by >7 log 10 CFU/g in a thigh muscle model. These data warrant further development of V-r in combatting E. coli , including resistant forms. 

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4. Coumarinolignans with Reactive Oxygen Species (ROS) and NF-κB Inhibitory Activities from the Roots of Waltheria indica

   https://doi.org/10.3390/molecules27103270  

   Liu, Feifei; Mallick, Sudipta; O’Donnell, Timothy J.; Rouzimaimaiti, Ruxianguli; Luo, Yuheng; Sun, Rui; Wall, Marisa; Wongwiwatthananukit, Supakit; Date, Abhijit; Silva, Dane Kaohelani; et al (May 2022, Molecules)

   Seven new coumarinolignans, walthindicins A–F (1a, 1b, 2–5, 7), along with five known analogs (6, 8–11), were isolated from the roots of Waltheria indica. The structures of the new compounds are determined by detailed nuclear magnetic resonance (NMR), circular dichroism (CD) with extensive computational support, and mass spectroscopic data interpretation. Compounds were tested for their antioxidant activity in Human Cervical Cancer cells (HeLa cells). Compounds 1a and 6 showed higher reactive oxygen species (ROS) inhibitory activity at 20 μg/mL when compared with other natural compound-based antioxidants such as ascorbic acid. Considering the role of ROS in nuclear-factor kappa B (NF-κB) activation, compounds 1a and 6 were evaluated for NF-κB inhibitory activity and showed a concentration-dependent inhibition in Human Embryonic Kidney 293 cells (Luc-HEK-293). 

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5. Novel Nitro-Heteroaromatic Antimicrobial Agents for the Control and Eradication of Biofilm-Forming Bacteria

   https://doi.org/10.3390/antibiotics10070855  

   Koenig, Heidi N.; Durling, Gregory M.; Walsh, Danica J.; Livinghouse, Tom; Stewart, Philip S. (July 2021, Antibiotics)

   The synthesis and biological activity of several novel nitrothiazole, nitrobenzothiazole, and nitrofuran containing antimicrobial agents for the eradication of biofilm-forming Gram-negative and Gram-positive pathogens is described. Nitazoxanide (NTZ), nitrofurantoin, and furazolidone are commercial antimicrobials which were used as models to show how structural modification improved activity toward planktonic bacteria via minimum inhibitory concentration (MIC) assays and biofilms via minimum biofilm eradication concentration (MBEC) assays. Structure–activity relationship (SAR) studies illustrate the ways in which improvements have been made to the aforementioned antimicrobial agents. It is of particular interest in this regard that the introduction of a chloro substituent at the 5-position of NTZ (analog 1b) resulted in marked activity enhancement, as did the replacement of the 2-acetoxy substituent in the latter compound with a basic amine group (analog 7b). It is also of importance that analog 4a, which is a simple methacrylamide, displayed noteworthy activity against S. epidermidis biofilms. These lead compounds identified to have high activity towards biofilms provide promise as starting points in future pro-drug studies. 

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