https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 Advancing the use of genome-wide association studies for drug repurposing https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:46016 Wed 09 Nov 2022 08:31:02 AEDT ]]> Repurposing azacitidine and carboplatin to prime immune checkpoint blockade-resistant melanoma for anti-PD-L1 re-challenge https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:49310 Thu 11 May 2023 14:39:28 AEST ]]> Gram-Positive and Gram-Negative Antibiotic Activity of Asymmetric and Monomeric Robenidine Analogues https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:44889 N′,2-bis((E)-4-chlorobenzylidene)hydrazine-1-carboximidhydrazide) and the introduction of imine alkyl substituents gave good antibiotic activity. Of note was the increased potency of two analogues against vancomycin-resistant Enterococci (VRE), one of which returned a MIC of 0.5 μg mL⁻¹. Five analogues were found to be equipotent or more potent than the lead 1. Introduction of an indole moiety resulted in the most active robenidine analogue against methicillin-resistant S. aureus (MRSA), with a MIC of 1.0 μg mL⁻¹. Imine C=NH isosteres (C=O/C=S) were inactive. Monomeric analogues were 16–64 μg mL⁻¹ active against MRSA and VRE. An analogue that lacks the terminal hydrazide NH moiety showed modest Gram-negative activity at 64 μg mL⁻¹. A 4-tert-butyl analogue was shown to be active against both Gram-positive and -negative strains at 16–64 μg mL⁻¹. In general, additional modifications with aromatic moieties was poorly tolerated, except with concomitant introduction of an imine C-alkyl group. The activity of these analogues against MRSA and VRE ranged from 8 μg mL−1 to inactive (MIC>128 μg mL⁻¹) with the naphthyl and indole analogues. Gram-negative activity was most promising with two compounds at 16 μg mL⁻¹ against E. coli. Against P. aeruginosa, the highest activity observed was with MIC values of 32 μg mL⁻¹ with another two analogues. Combined, these findings support the further development of the (E)-2-benzylidenehydrazine-1-carboximidamide scaffold as a promising scaffold for the development of antibiotics against Gram-positive and Gram-negative strains.]]> Mon 24 Oct 2022 14:46:25 AEDT ]]> Genetics-informed precision treatment formulation in schizophrenia and bipolar disorder https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:50980 Mon 14 Aug 2023 15:24:38 AEST ]]> Genetic association and causal inference converge on hyperglycaemia as a modifiable factor to improve lung function https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:47250 Fri 16 Dec 2022 12:29:24 AEDT ]]>