David Hibbs

Comprehensive Characterization of a Systematic Library of Alkyl and Alicyclic Synthetic Cannabinoids Related to CUMYL-PICA, CUMYL-BUTICA, CUMYL-CBMICA, and CUMYL-PINACA

Publisher: American Chemical Society (ACS)

Date: 19-12-2022

DOI: 10.1021/ACSCHEMNEURO.2C00408

Structure–activity relationships of valine, tert-leucine, and phenylalanine amino acid-derived synthetic cannabinoid receptor agonists related to ADB-BUTINACA, APP-BUTINACA, and ADB-P7AICA

Publisher: Royal Society of Chemistry (RSC)

Date: 2022

DOI: 10.1039/D1MD00242B

Abstract: Synthetic cannabinoid receptor agonists (SCRAs) remain one the most prevalent classes of new psychoactive substances (NPS) worldwide, and ex les are generally poorly characterised at the time of first detection.

Using Electron Density to Predict Synthon Formation in a 4-Hydroxybenzoic Acid: 4,4′-Bipyridine Cocrystal

Publisher: American Chemical Society (ACS)

Date: 11-01-2018

DOI: 10.1021/ACS.CGD.7B01676

The Antifungal and Synergistic Effect of Bisphosphonates in Cryptococcus

Publisher: American Society for Microbiology

Date: 20-01-2021

DOI: 10.1128/AAC.01753-20

Abstract: New treatment strategies are required for cryptococcosis, a leading mycosis in HIV-AIDS patients. Following the identification of Cryptococcus proteins differentially expressed in response to fluconazole, we targeted farnesyl pryrophosphate synthetase (FPPS), an enzyme in the squalene biosynthesis pathway, using nitrogenous bisphosphonates. We hypothesized that these would disrupt squalene synthesis and thereby produce synergy with fluconazole, which acts on a downstream pathway that requires squalene.

An experimental and theoretical charge density study of theophylline and malonic acid cocrystallization

Publisher: Royal Society of Chemistry (RSC)

Date: 2022

DOI: 10.1039/D1RA08389A

Abstract: In this study, the 1:1 cocrystal of theophylline and malonic acid originally engineered by Trask undergoes charge density analysis to rationalise the chemical change process seen throughout crystallisation.

Non-Antigenic Modulation of Antigen Receptor (TCR) Cβ-FG Loop Modulates Signalling: Implications of External Factors Influencing T-Cell Responses

Publisher: MDPI AG

Date: 26-05-2023

DOI: 10.3390/IJMS24119334

Abstract: T-cell recognition of antigens is complex, leading to biochemical and cellular events that impart both specific and targeted immune responses. The end result is an array of cytokines that facilitate the direction and intensity of the immune reaction—such as T-cell proliferation, differentiation, macrophage activation, and B-cell isotype switching—all of which may be necessary and appropriate to eliminate the antigen and induce adaptive immunity. Using in silico docking to identify small molecules that putatively bind to the T-cell Cβ-FG loop, we have shown in vitro using an antigen presentation assay that T-cell signalling is altered. The idea of modulating T-cell signalling independently of antigens by directly targeting the FG loop is novel and warrants further study.

A Guide to In Silico Drug Design

Publisher: MDPI AG

Date: 23-12-2023

DOI: 10.3390/PHARMACEUTICS15010049

Abstract: The drug discovery process is a rocky path that is full of challenges, with the result that very few candidates progress from hit compound to a commercially available product, often due to factors, such as poor binding affinity, off-target effects, or physicochemical properties, such as solubility or stability. This process is further complicated by high research and development costs and time requirements. It is thus important to optimise every step of the process in order to maximise the chances of success. As a result of the recent advancements in computer power and technology, computer-aided drug design (CADD) has become an integral part of modern drug discovery to guide and accelerate the process. In this review, we present an overview of the important CADD methods and applications, such as in silico structure prediction, refinement, modelling and target validation, that are commonly used in this area.

A comparison of the experimental and theoretical charge density distributions in two polymorphic modifications of piroxicam

Publisher: Royal Society of Chemistry (RSC)

Date: 2016

DOI: 10.1039/C6CP02690G

Abstract: Experimental charge density analysis of two piroxicam polymorphs has found a redistribution of charge to a non-classical zwitterionic form.

Rapid access to N-(indol-2-yl)amides and N-(indol-3-yl)amides as unexplored pharmacophores

Publisher: Royal Society of Chemistry (RSC)

Date: 2017

DOI: 10.1039/C6OB02622B

Abstract: Preparation of N -(indol-2-yl)amides and N -(indol-3-yl)amides are scarce in the scientific literature due to unstable intermediates impeding current reported syntheses.

Exploring the Solubility of the Carbamazepine–Saccharin Cocrystal: A Charge Density Study

Publisher: American Chemical Society (ACS)

Date: 13-12-2018

DOI: 10.1021/ACS.CGD.8B01111

Delivering anion transporters to lipid bilayers in water

Publisher: Royal Society of Chemistry (RSC)

Date: 2021

DOI: 10.1039/D1OB02041B

Abstract: Cyclodextrins have been employed as delivery agents for lipophilic anion transporters, which allow their incorporation into lipid bilayers without using an organic solvent or pre-incorporation.

Identification of dual PPARα/γ agonists and their effects on lipid metabolism

Publisher: Elsevier BV

Date: 12-2015

DOI: 10.1016/J.BMC.2015.11.013

Abstract: The three peroxisome proliferator-activated receptor (PPAR) isoforms PPARα, PPARγ and PPARδ, play central roles in lipid metabolism and glucose homeostasis. Dual PPARα/γ agonists, which stimulate both PPARα and PPARγ isoforms to similar extents, are gaining popularity as it is believed that they are able to ameliorate the unwanted side effects of selective PPARα and PPARγ agonists and may also be used to treat dyslipidemia and type 2 diabetes mellitus simultaneously. In this study, virtual screening of natural product libraries, using both structure-based and ligand-based drug discovery approaches, identified ten potential dual PPARα/γ agonist lead compounds (9-13 and 16-20). In vitro assays confirmed these compounds to show no statistically significant toxicity to cells, with the exception of compound 12 which inhibited cell growth to 74.5%±3.5 and 54.1%±3.7 at 50μM and 100μM, respectively. In support of their potential as dual PPARα/γ agonists, all ten compounds upregulated the expression of cholesterol transporters ABCA1 and ABCG1 in THP-1 macrophages, with indoline derivative 16 producing the greatest elevation (2.3-fold 3.3-fold, respectively). Furthermore, comparable to the activity of established PPARα and PPARγ agonists, compound 16 stimulated triacylglycerol accumulation during 3T3-L1 adipocyte differentiation as well as fatty acid β-oxidation in HuH7 hepatocytes.

Methods for the detection and identification of pathogenic bacteria: past, present, and future

Publisher: Royal Society of Chemistry (RSC)

Date: 2017

DOI: 10.1039/C6CS00693K

Abstract: In this tutorial review, the techniques involved in the detection of pathogenic bacteria are described.

Novel diagnostics for point-of-care bacterial detection and identification

Publisher: Royal Society of Chemistry (RSC)

Date: 2019

DOI: 10.1039/C9RA03118A

Abstract: The WHO global action plan on antimicrobial resistance outlines the need for new diagnostic tools. Point-of-care testing for bacterial infections would enable clinically meaningful interventions using methods that are rapid, low-cost, easy-to-operate, and portable.

Strategies to develop selective CB2 receptor agonists from indole carboxamide synthetic cannabinoids

Publisher: Elsevier BV

Date: 10-2019

DOI: 10.1016/J.EJMECH.2019.07.036

Abstract: Activation of the CB

NNL-3: A Synthetic Intermediate or a New Class of Hydroxybenzotriazole Esters with Cannabinoid Receptor Activity?

Publisher: American Chemical Society (ACS)

Date: 22-10-2021

DOI: 10.1021/ACSCHEMNEURO.1C00348

Putative Synthetic Cannabinoids MEPIRAPIM, 5F-BEPIRAPIM (NNL-2), and Their Analogues Are T-Type Calcium Channel (Ca

Publisher: American Chemical Society (ACS)

Date: 20-04-2022

DOI: 10.1021/ACSCHEMNEURO.1C00822

Abstract: Synthetic cannabinoid receptor agonists (SCRAs) are a large and growing class of new psychoactive substances (NPSs). Two recently identified compounds, MEPIRAPIM and 5F-BEPIRAPIM (NNL-2), have not been confirmed as agonists of either cannabinoid receptor subtype but share structural similarities with both SCRAs and a class of T-type calcium channel (Ca

The discovery of a potent and selective pyrazolo-[2,3-e]-[1,2,4]-triazine cannabinoid type 2 receptor agonist

Publisher: Elsevier BV

Date: 2021

DOI: 10.1016/J.EJMECH.2020.113087

First Nondiscriminating Translocator Protein Ligands Produced from a Carbazole Scaffold

Publisher: American Chemical Society (ACS)

Date: 16-08-2019

DOI: 10.1021/ACS.JMEDCHEM.9B00980

Abstract: Development of neuroinflammation agents targeting the translocator protein (TSPO) has been hindered by a common single nucleotide polymorphism (A147T) at which TSPO ligands commonly lose affinity. To this end, carbazole acetamide scaffolds were synthesized and structure activity relationships elaborated to explore the requirements for high-affinity binding to both TSPO wild type (WT) and the polymorphic TSPO A147T. This study reports high binding affinity and nondiscriminating TSPO ligands.

Defining Steric Requirements at CB1 and CB2 Cannabinoid Receptors Using Synthetic Cannabinoid Receptor Agonists 5F-AB-PINACA, 5F-ADB-PINACA, PX-1, PX-2, NNL-1, and Their Analogues

Publisher: American Chemical Society (ACS)

Date: 11-04-2022

DOI: 10.1021/ACSCHEMNEURO.2C00034

Abstract: Synthetic cannabinoid receptor agonists (SCRAs) are a erse class of new psychoactive substances (NPS). They commonly comprise

Synthesis and Preclinical Evaluation of Fluorinated 5-Azaindoles as CB2 PET Radioligands

Publisher: American Chemical Society (ACS)

Date: 27-07-2023

DOI: 10.1021/ACSCHEMNEURO.3C00345

Exploring the excited-state charge transfer fluorescence profile of 7-hydroxycoumarin and 2-methylimidazole - a combined X-ray diffraction and theoretical approach

Publisher: Royal Society of Chemistry (RSC)

Date: 2022

DOI: 10.1039/D2CP01235A

Abstract: This study investigated and rationalised the fluorescence modulation of 7-hydroxycoumarin in response to changing concentrations of 2-methylimidazole using low-cost quantum mechanical calculations from single crystal X-ray geometries.

The role of adjuvants in overcoming antibacterial resistance due to enzymatic drug modification

Publisher: Royal Society of Chemistry (RSC)

Date: 2022

DOI: 10.1039/D2MD00263A

Abstract: Enzymatic drug deactivation is an important contributor to bacterial resistance. Adjuvants which inhibit the β-lactamases help maintain the efficacy of the β-lactams, demonstrating the potential for this strategy for other antibacterial classes.

Exploring the Binding of Barbital to a Synthetic Macrocyclic Receptor. A Charge Density Study

Publisher: American Chemical Society (ACS)

Date: 26-02-2018

DOI: 10.1021/ACS.JPCA.7B11674

Abstract: Experimental charge density distribution studies, complemented by quantum mechanical theoretical calculations, of a host-guest system composed of a macrocycle (1) and barbital (2) in a 1:1 ratio (3) have been carried out via high-resolution single-crystal X-ray diffraction. The data were modeled using the conventional multipole model of electron density according to the Hansen-Coppens formalism. The asymmetric unit of macrocycle 1 contained an intraannular ethanol molecule and an extraannular acetonitrile molecule, and the asymmetric unit of 3 also contained an intraannular ethanol molecule. Visual comparison of the conformations of the macrocyclic ring shows the rotation by 180° of an amide bond attributed to competitive hydrogen bonding. It was found that the intraannular and extraannular molecules inside were orientated to maximize the number of hydrogen bonds present, with the presence of barbital in 3 resulting in the greatest stabilization. Hydrogen bonds ranging in strength from 4 to 70 kJ mol

Tubulin-Binding 3,5-Bis(styryl)pyrazoles as Lead Compounds for the Treatment of Castration-Resistant Prostate Cancer

Publisher: American Society for Pharmacology & Experimental Therapeutics (ASPET)

Date: 02-04-2020

DOI: 10.1124/MOL.119.118539

Understanding Hygroscopicity of Theophylline via a Novel Cocrystal Polymorph: A Charge Density Study

Publisher: American Chemical Society (ACS)

Date: 03-11-2021

DOI: 10.1021/ACS.JPCA.0C09536

Abstract: The charge density distribution in a novel cocrystal (1) complex of 1,3-dimethylxanthine (theophylline) and propanedioic acid (malonic acid) has been determined. The molecules crystallize in the triclinic, centrosymmetric space group

Analyzing Hydration Differences in Cocrystal Polymorphs: High-Resolution X-ray Investigation of Caffeine-Glutaric Acid Cocrystals

Publisher: American Chemical Society (ACS)

Date: 19-07-2021

DOI: 10.1021/ACS.CGD.1C00358

Cardiff University Cardiff School Of Chemistry

Location: United Kingdom of Great Britain and Northern Ireland

View Organisation

Discovery Projects - Grant ID: DP0556144

Start Date: 2005

End Date: 10-2010

Amount: $780,000.00

Funder: Australian Research Council

Discovery Projects - Grant ID: DP0208100

Start Date: 07-2002

End Date: 06-2005

Amount: $200,000.00

Funder: Australian Research Council

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0346733

Start Date: 01-2003

End Date: 12-2004

Amount: $399,466.00

Funder: Australian Research Council

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0775720

Start Date: 06-2007

End Date: 06-2008

Amount: $100,000.00

Funder: Australian Research Council

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE210100144

Start Date: 2021

End Date: 12-2022

Amount: $1,225,000.00

Funder: Australian Research Council