ABSTRACT
Antimicrobial drug resistance is currently one of the most critical health issues. Pathogens resistant to last-resort antibiotics are increasing, and very few effective antibacterial agents have been introduced in recent years. The promising drug candidates are often discontinued in the primary stages of the drug discovery pipeline due to their unspecific reactivity (PAINS), toxicity, insufficient stability, or low water solubility. In this work, we investigated a series of substituted N-oxazolyl- and N-thiazolylcarboxamides of various pyridinecarboxylic acids. Final compounds were tested against several microbial species. In general, oxazole-containing compounds showed high activity against mycobacteria, especially Mycobacterium tuberculosis (best MICH37Ra = 3.13 µg/mL), including the multidrug-resistant strains. Promising activities against various bacterial and fungal strains were also observed. None of the compounds was significantly cytotoxic against the HepG2 cell line. Experimental measurement of lipophilicity parameter log k'w and water solubility (log S) confirmed significantly (typically two orders in logarithmic scale) increased hydrophilicity/water solubility of oxazole derivatives in comparison with their thiazole isosteres. Mycobacterial ß-ketoacyl-acyl carrier protein synthase III (FabH) was suggested as a probable target by molecular docking and molecular dynamics simulations.
ABSTRACT
Digital twin (DT) is an emerging key technology that enables sophisticated interaction between physical objects and their virtual replicas, with applications in almost all engineering fields. Although it has recently gained significant attraction in both industry and academia, so far it has no unanimously adopted and established definition. One may therefore come across many definitions of what DT is and how to create it. DT can be designed for an existing process and help us to improve it. Another possible approach is to create the DT for a brand new device. In this case, it can reveal how the system would behave in given conditions or when controlled. One of purposes of a DT is to support the commissioning of devices. So far, recognized and used techniques to make the commissioning more effective are virtual commissioning and hybrid commissioning. In this article, we present a concept of hybrid virtual commissioning. This concept aims to point out the possibility to use real devices already at the stage of virtual commissioning. It is introduced in a practical case study of a robotic manipulator with machine vision controlled with a programmable logic controller in a pick-and-place application. This study presents the benefits that stem from the proposed approach and also details when it is convenient to use it.