Shapeshifting bullvalene-linked vancomycin dimers as effective antibiotics against multidrug-resistant gram-positive bacteria.

The alarming rise in superbugs that are resistant to drugs of last resort, including vancomycin-resistant enterococci and staphylococci, has become a significant global health hazard. Here, we report the click chemistry synthesis of an unprecedented class of shapeshifting vancomycin dimers (SVDs) that display potent activity against bacteria that are resistant to the parent drug, including the ESKAPE pathogens, vancomycin-resistant (VRE), methicillin-resistant (MRSA), as well as vancomycin-resistant (VRSA). The shapeshifting modality of the dimers is powered by a triazole-linked bullvalene core, exploiting the dynamic covalent rearrangements of the fluxional carbon cage and creating ligands with the capacity to inhibit bacterial cell wall biosynthesis.

Cage hydrocarbons as linkers in dimeric drug design: Case studies with trimethoprim and tedizolid.

The looming threat of a "post-antibiotic era" has been caused by a rapid rise in antibacterial resistance and subsequent depletion of effective antibiotic agents in the clinic. An efficient strategy to address this shortfall lies in the reengineering of pre-existing and commercially available antibiotic drugs. This is exemplified by dimerization, a design concept in which two pharmacophores are covalently linked to form a new chemical entity.

Biosynthesis of uridine diphosphate N-Acetylglucosamine: An underexploited pathway in the search for novel antibiotics?

Although the prevalence of antibiotic resistance is increasing at an alarming rate, there are a dwindling number of effective antibiotics available. Thus, the development of novel antibacterial agents should be of utmost importance. Peptidoglycan biosynthesis has been and is still an attractive source for antibiotic targets; however, there are several components that remain underexploited.

Antibacterial silver and gold complexes of imidazole and 1,2,4-triazole derived N-heterocyclic carbenes.

A series of gold(I) (4a-4h, 5a-5b) and silver(I) (3a-3h) complexes of 1,2,4-triazolylidene and imidazolylidene based N-heterocyclic carbene ligands were prepared and the antibacterial activities of these complexes have been evaluated. The complexes were characterised using H-NMR, C-NMR, HRMS and in the cases of 3a, 3c, 4b and 5b by X-ray crystallography. The gold(I) complexes with phenyl substituents (4a-4d) were found to have potent antibacterial activity against Gram-positive bacteria, with the complexes of the 1,2,4-triazolylidene ligands being more active (4c, MIC = 4-8 μg mL against and 2 μg mL against ) than the analogous imidazolylidene complexes 4a and 4b (4a, MIC = 64 μg mL against and 2-4 μg mL against ).

Theories Informing eHealth Implementation: Systematic Review and Typology Classification.

Background: Theory-guided approaches to implementation science have informed translation efforts and the acceptance of eHealth (digital health) interventions in clinical care. However, there is scarce evidence on which theories are best suited to addressing the inherent complexity of eHealth implementation.

Objective: The objectives of this systematic review are to identify theories that inform and explain eHealth implementation and to classify these theories using the typology by Sovacool and Hess for theories of sociotechnical change.

Examining word association networks: A cross-country comparison of women's perceptions of HPV testing and vaccination.

In this study, we examined the perceptual associations women hold with regard to cervical cancer testing and vaccination across two countries, the U.S. and Australia.

An Examination of Not-For-Profit Stakeholder Networks for Relationship Management: A Small-Scale Analysis on Social Media.

Using a small-scale descriptive network analysis approach, this study highlights the importance of stakeholder networks for identifying valuable stakeholders and the management of existing stakeholders in the context of mental health not-for-profit services. We extract network data from the social media brand pages of three health service organizations from the U.S.