Polymyxin B Activity Rescue by (-)-Camphene-Based Thiosemicarbazide Against Carbapenem-Resistant Enterobacterales.

Due to the significant shortage of therapeutic options for carbapenem-resistant Enterobacterales (CRE) infections, new drugs or therapeutic combinations are urgently required. We show in this study that (-)-camphene-based thiosemicarbazide (TSC) may act synergistically with polymyxin B (PMB) against CRE, rescuing the activity of this antimicrobial. With the specific aim of a better molecular understanding of this effect caused by the presence of TSC, theoretical calculations were also performed in this study. Based on these findings, it is concluded that the presence of TSC moieties contributes to significant changes in the hydrogen atom charge of PMB structure, which trend more positives for the PMB/TSC system studied. This could lead to the formation of stronger hydrogen bonds in the Enterobacterales active site and, thus contribute to a molecular understanding of the PMB rescue of activity promoted by the presence of TSC moiety. As such, the clinical potential of these drug combinations requires further evaluation.

Theoretical insights into the effect of halogenated substituent on the electronic structure and spectroscopic properties of the favipiravir tautomeric forms and its implications for the treatment of COVID-19.

In this study, we systematically investigated the electronic structure, spectroscopic (nuclear magnetic resonance, infrared, Raman, electron ionization mass spectrometry, UV-Vis, circular dichroism, and emission) properties, and tautomerism of halogenated favipiravir compounds (fluorine, chlorine, and bromine) from a computational perspective. Additionally, the effects of hydration on the proton transfer mechanism of the tautomeric forms of the halogenated favipiravir compounds are discussed. Our results suggest that spectroscopic properties allow for the elucidation of such tautomeric forms. As is well-known, the favipiravir compound has excellent antiviral properties and hence was recently tested for the treatment of new coronavirus (SARS-CoV-2). Through in silico modeling, in the current study, we evaluate the role of such tautomeric forms in order to consider the effect of drug-metabolism in the inhibition process of the main protease (Mpro) and RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 virus. According to the molecular docking, all halogenated compounds presented a better interaction energy than the co-crystallized active ligand (-3.5 kcal mol-1) in the viral RdRp, in both wild-type (-6.3 to -6.5 kcal mol-1) and variant (-5.4 to -5.6 kcal mol-1) models. The variant analyzed for RdRp (Y176C) decreases the affinity of the keto form of the compounds in the active site, and prevented the ligands from interacting with RNA. These findings clearly indicated that all these compounds are promising as drug candidates for this molecular target.

Effects of chemical substitution on the structural and optical properties of α-Ag2-2xNixWO4 (0 ≤ x ≤ 0.08) solid solutions.

In this work, we investigated the effects of chemical substitution on the structural, electronic, and optical properties of α-Ag2-2xNixWO4 (0 ≤ x ≤ 0.08) solid solutions prepared by a facile microwave-assisted hydrothermal method. The results showed that the increase of Ni concentration in α-Ag2WO4 microcrystals as a host matrix caused a morphological transformation and a shift of the electronic and optical properties. Based on first principles calculations and using Wulff's construction, particle shapes and their transformations in α-Ag2WO4 and α-Ag2-2xNixWO4 can be affected by controlling the ratios of surface energy values between the different facets. In addition, theoretical calculations revealed that Ni substitution in α-Ag2WO4 is more favorable in the Ag2 and Ag4 positions, in which the local coordination of Ag atoms corresponds to clusters with coordination numbers of seven and four, respectively. This behavior could be related to the degree of medium-range structural disorder in α-Ag2-2xNixWO4 crystals. The experimental results were correlated with theoretical simulations to achieve a deeper understanding of the relationship between morphology and properties. These results provide the basis for a rational design for the compositional modulation of structural and optical properties.