In vitro antibacterial activity of rhodanine derivatives against pathogenic clinical isolates

Bacterial infections present a serious challenge to healthcare practitioners due to the emergence of resistance to numerous conventional antibacterial drugs. Therefore, new bacterial targets and new antimicrobials are unmet medical needs. Rhodanine derivatives have been shown to possess potent antimicrobial activity via a novel mechanism. However, their potential use as antibacterials has not been fully examined. In this study, we determined the spectrum of activity of seven rhodanine derivatives (compounds Rh 1-7) against clinical isolates of Gram-positive and Gram-negative bacterial strains and Candida albicans. We also synthesized and tested three additional compounds, ethyl ester and amide of rhodanine 2 (Rh 8 and Rh 10, respectively) and ethyl ester of rhodanine 3 (Rh 9) to determine the significance of the carboxyl group modification towards antibacterial activity and human serum albumin binding. A broth microdilution assay confirmed Rh 1-7 exhibit bactericidal activity against Gram-positive pathogens. Rh 2 had significant activity against various vancomycin- resistant (MIC90 = 4 μM) and methicillin-resistant (MIC90 = 4 μM) Staphylococcus aureus (VRSA and MRSA), Staphylococcus epidermidis (MIC = 4 μM) and vancomycinresistant Enterococcus (VRE) strains (MIC90 = 8 μM). The rhodanine compounds exhibited potent activity against Bacillus spp., including Bacillus anthracis, with MIC range of 2-8 μM. In addition, they had potent activity against Clostridium difficile. The most potent compound, Rh 2, at 4 and 8 times its MIC, significantly decreased S. epidermidis biofilm mass by more than 35% and 45%, respectively. None of the rhodanine compounds showed antimicrobial activity (MIC \u3e 128 μM) against various 1) Gram-negative pathogens (Acinetobacter baumannii, Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa, and Salmonella Typhimurium) or 2) strains of Candida albicans (MIC \u3e 64 μM). The MTS assay confirmed that rhodanines were not toxic to mouse murine macrophage (J774.1A) up to 64 μM, human keratinocytes (HaCat) up to 32 μM, and human ileocecal colorectal cell (HRT-18) up to 128 μM. Overall, these data suggest that certain rhodanine compounds may have potential use for the treatment of several multidrug-resistant Gram-positive bacterial infections. © 2016 AbdelKhalek et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Oral and dermal toxicity of alkenones extracted from Isochrysis species

Author Posting. © Bioscience Research Institute, 2020. This article is posted here by permission of Bioscience Research Institute for personal use, not for redistribution. The definitive version was published in McIntosh, K., Sarver, J., Mell, K., Terrero, D. J., Ashby, C. R., Reddy, C., O’Neil, G., Ramapuram, J. B., & Tiwari, A. K. Oral and dermal toxicity of alkenones extracted from Isochrysis species. Frontiers in Bioscience-Landmark, 25(5), (2020): 817–837, https://doi.org/10.2741/4836.Isochrysis is commercially available marine algae used for animal feed, human nutrient supplements, and biodiesel. The Isochrysis species is one of five genera of haptophytes that produces unique, long-chain lipids known as alkenones that are promising new ingredients for green cosmetics, personal care products and pharmaceutical delivery. However, there is a lack of toxicity data for alkenones in animals, thus limiting their use in humans. In this study, we performed acute oral, acute dermal, and repeated 28-day dermal toxicity studies, using female SAS Sprague Dawley Rats. Our behavioral studies indicated that the specific alkenones had no overt behavioural effects at oral doses up to 4000 mg/kg. In the acute and chronic dermal toxicity studies, the alkenones produced less irritation and did not significantly damage the skin based on the Draize skin reaction scale and trans-epidermal water loss readings compared to the positive control, 1% sodium lauryl sulfate. Overall, our results indicated that alkenones are safe in Sprague Dawley rats, suggesting that they could be used for both oral and dermal formulations, although additional studies will be required.This work was supported by the Marine Biological Laboratory Woods Hole Oceanographic Institute (WHOI) under grant (N-126665-01, 2017), Washington Research Foundation, and University of Toledo start-up funding under a grant (F110760) to A.K.T. The authors declare no conflict of interest

Mood and cognition in healthy older European adults: the Zenith study

YesBackground: The study aim was to determine if state and trait intra-individual measures of everyday affect predict cognitive functioning in healthy older community dwelling European adults (n = 387), aged 55-87 years. Methods: Participants were recruited from centres in France, Italy and Northern Ireland. Trait level and variability in positive and negative affect (PA and NA) were assessed using self-administered PANAS scales, four times a day for four days. State mood was assessed by one PANAS scale prior to assessment of recognition memory, spatial working memory, reaction time and sustained attention using the CANTAB computerized test battery. Results: A series of hierarchical regression analyses were carried out, one for each measure of cognitive function as the dependent variable, and socio-demographic variables (age, sex and social class), state and trait mood measures as the predictors. State PA and NA were both predictive of spatial working memory prior to looking at the contribution of trait mood. Trait PA and its variability were predictive of sustained attention. In the final step of the regression analyses, trait PA variability predicted greater sustained attention, whereas state NA predicted fewer spatial working memory errors, accounting for a very small percentage of the variance (1-2%) in the respective tests. Conclusion: Moods, by and large, have a small transient effect on cognition in this older sample

Modelling human choices: MADeM and decision‑making

Research supported by FAPESP 2015/50122-0 and DFG-GRTK 1740/2. RP and AR are also part of the Research, Innovation and Dissemination Center for Neuromathematics FAPESP grant (2013/07699-0). RP is supported by a FAPESP scholarship (2013/25667-8). ACR is partially supported by a CNPq fellowship (grant 306251/2014-0)

Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of rhodanine compounds (μM) against methicillin-resistant <i>Staphylococcus aureus</i> (MRSA).

<p>Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of rhodanine compounds (μM) against methicillin-resistant <i>Staphylococcus aureus</i> (MRSA).</p

Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of rhodanine compounds (μM) against <i>Mycobacterium smegmatis</i>.

<p>Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of rhodanine compounds (μM) against <i>Mycobacterium smegmatis</i>.</p

MICs of Rhodanines against Gram negative pathogens in the presence and absence of polymixin B nonapeptide (PMBN) (4 μg/mL).

<p>MICs of Rhodanines against Gram negative pathogens in the presence and absence of polymixin B nonapeptide (PMBN) (4 μg/mL).</p

Minimum inhibitory concentration (MIC) of rhodanine compounds against <i>Candida albicans</i>.

<p>Minimum inhibitory concentration (MIC) of rhodanine compounds against <i>Candida albicans</i>.</p