The “NeuroDante project”: neurometric measurements of subject’s reaction to literary auditory stimuli from Dante’s “Divina Commedia”

This work is a pilot study that used neurometric indexes during the listening of selected pieces of Dante‟s “Divina Commedia” in 20 participants. Half of them had a literary formation (Humanist; university students of litera-ture) while the other half of is attending other university courses (Not Human-ist). The study applied the electroencephalographic (EEG) rhythms variations, the heart rate (HR) and galvanic skin response (GSR) during the listening of the excerpts. The neurometric indexes here employed were the ApproachWith-drawal (AW), the cerebral Effort (CE) and the Emotional indexes (EI). Results for the comparisons of the estimated AW, CE and EI related to the perception of the canticas showed as the Humanist group reported higher AW and EI values when compared to the Not Humanist sample (p<0.03 and p<0.01, re-spectively). Results suggest that the perception of the aesthetic experience is significantly modulated by the previous specific knowledge experienced by the participants. Finally, results of this kind of research could find application in the implementation of software and devices based on symbiotic relation with the perspective reader or listener of a literature opera, in order to personalize and maximize the fruition of them

4-Alkyl-1,2,4-triazole-3-thione analogues as metallo-β-lactamase inhibitors

In Gram-negative bacteria, the major mechanism of resistance to β-lactam antibiotics is the production of one or several β-lactamases (BLs), including the highly worrying carbapenemases. Whereas inhibitors of these enzymes were recently marketed, they only target serine-carbapenemases (e.g. KPC-type), and no clinically useful inhibitor is available yet to neutralize the class of metallo-β-lactamases (MBLs). We are developing compounds based on the 1,2,4-triazole-3-thione scaffold, which binds to the di-zinc catalytic site of MBLs in an original fashion, and we previously reported its promising potential to yield broad-spectrum inhibitors. However, up to now only moderate antibiotic potentiation could be observed in microbiological assays and further exploration was needed to improve outer membrane penetration. Here, we synthesized and characterized a series of compounds possessing a diversely functionalized alkyl chain at the 4-position of the heterocycle. We found that the presence of a carboxylic group at the extremity of an alkyl chain yielded potent inhibitors of VIM-type enzymes with Ki values in the μM to sub-μM range, and that this alkyl chain had to be longer or equal to a propyl chain. This result confirmed the importance of a carboxylic function on the 4-substituent of 1,2,4-triazole-3-thione heterocycle. As observed in previous series, active compounds also preferentially contained phenyl, 2-hydroxy-5-methoxyphenyl, naphth-2-yl or m-biphenyl at position 5. However, none efficiently inhibited NDM-1 or IMP-1. Microbiological study on VIM-2-producing E. coli strains and on VIM-1/VIM-4-producing multidrug-resistant K. pneumoniae clinical isolates gave promising results, suggesting that the 1,2,4-triazole-3-thione scaffold worth continuing exploration to further improve penetration. Finally, docking experiments were performed to study the binding mode of alkanoic analogues in the active site of VIM-2. © 2021 Elsevier Inc

Optimization of 1,2,4-triazole-3-thiones towards broad-spectrum metallo-β-lactamase inhibitors showing potent synergistic activity on VIM- and NDM-1-producing clinical isolates

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