New Auranofin Analogs with Antibacterial Properties against Burkholderia Clinical Isolates

Maydaniuk, Dustin; Wu, Bin; Truong, Dang; Liyanage, Sajani H.; Hogan, Andrew M.; Yap, Zhong Ling; Yan, Mingdi; Cardona, Silvia T.

doi:10.3390/antibiotics10121443

Cited by 6 publications

(6 citation statements)

References 57 publications

(117 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…All treatments substantially improved larval survival relative to no treatment controls, demonstrating the model’s usefulness in screening novel anti- Burkholderia agents (Thomas et al 2013 ). Finally, two auranofin analogues active against Burkholderia clinical isolates in vitro were of low toxicity in G. mellonella , warranting further investigation for their therapeutic potential (Maydaniuk et al 2021 ).…”

Section: Burkholderia Pseudomallei and Burkholderi...mentioning

confidence: 99%

Galleria mellonella–intracellular bacteria pathogen infection models: the ins and outs

Asai

Newton

et al. 2023

FEMS Microbiology Reviews

View full text Add to dashboard Cite

Galleria mellonella (greater wax moth) larvae are used widely as surrogate infectious disease models, due to ease of use and the presence of an innate immune system functionally similar to that of vertebrates. Here we review G. mellonella-human intracellular bacteria pathogen infection models from the genera Burkholderia, Coxiella, Francisella, Listeria, and Mycobacterium. For all genera, G. mellonella use has increased understanding of host-bacterial interactive biology, particularly through studies comparing the virulence of closely related species and/or wild-type versus mutant pairs. In many cases, virulence in G. mellonella mirrors that found in mammalian infection models, although it is unclear whether the pathogenic mechanisms are the same. The use of G. mellonella larvae has speeded up in vivo efficacy and toxicity testing of novel antimicrobials to treat infections caused by intracellular bacteria: an area that will expand since the FDA no longer requires animal testing for licensure. Further use of G. mellonella-intracellular bacteria infection models will be driven by advances in G. mellonella genetics, imaging, metabolomics, proteomics, and transcriptomic methodologies, alongside the development and accessibility of reagents to quantify immune markers, all of which will be underpinned by a fully annotated genome.

show abstract

Section: Burkholderia Pseudomallei and Burkholderi...mentioning

confidence: 99%

Galleria mellonella–intracellular bacteria pathogen infection models: the ins and outs

Asai

Newton

et al. 2023

FEMS Microbiology Reviews

View full text Add to dashboard Cite

show abstract

“…The drug combinations with synergy scores above 15 calculated by all models were considered synergistic; between -5 and 15 were deemed to be additive, whereas synergy scores below -15 were considered antagonistic. Synergy scores represent the mean response deviated from the reference model due to interactions between the combined drugs [ 14 , 56 ].…”

Section: Methodsmentioning

confidence: 99%

A machine learning model trained on a high-throughput antibacterial screen increases the hit rate of drug discovery

Rahman

Liu²,

Sturm³

et al. 2022

PLoS Comput Biol

Self Cite

View full text Add to dashboard Cite

Screening for novel antibacterial compounds in small molecule libraries has a low success rate. We applied machine learning (ML)-based virtual screening for antibacterial activity and evaluated its predictive power by experimental validation. We first binarized 29,537 compounds according to their growth inhibitory activity (hit rate 0.87%) against the antibiotic-resistant bacterium Burkholderia cenocepacia and described their molecular features with a directed-message passing neural network (D-MPNN). Then, we used the data to train an ML model that achieved a receiver operating characteristic (ROC) score of 0.823 on the test set. Finally, we predicted antibacterial activity in virtual libraries corresponding to 1,614 compounds from the Food and Drug Administration (FDA)-approved list and 224,205 natural products. Hit rates of 26% and 12%, respectively, were obtained when we tested the top-ranked predicted compounds for growth inhibitory activity against B. cenocepacia, which represents at least a 14-fold increase from the previous hit rate. In addition, more than 51% of the predicted antibacterial natural compounds inhibited ESKAPE pathogens showing that predictions expand beyond the organism-specific dataset to a broad range of bacteria. Overall, the developed ML approach can be used for compound prioritization before screening, increasing the typical hit rate of drug discovery.

show abstract

“…316 derivatives are active against Helicobacter pylori and bacteria from the Burkholderia genus. 317,318 Another study has also shown that auranofin inhibited, in a concentration-dependent manner, the growth of Helicobacter pylori TrxR (Gram-negative bacteria) and showed synergistic or additive effect with known H. pylori antibiotics such as amoxicillin or metronidazole and clarithromycin. Also, when the phosphane ligand on auranofin was replaced by Nheterocyclic carbene as shown in Figure 20, stability and inhibitory activity of the complexes were not altered greatly, and they show reduced in vitro toxicity.…”

Section: Antibacterial Gold Complexesmentioning

confidence: 99%

“…Their study also revealed that the thiol ligand is necessary for the bactericidal activity of both Gram-positive and Gram-negative bacteria . Other reports from this lab have also shown that auranofin and its derivatives are active against Helicobacter pylori and bacteria from the Burkholderia genus. , …”

Section: Therapeutic Gold Complexesmentioning

confidence: 99%

Next Generation Gold Drugs and Probes: Chemistry and Biomedical Applications

et al. 2023

View full text Add to dashboard Cite

The gold drugs, gold sodium thiomalate (Myocrisin), aurothioglucose (Solganal), and the orally administered auranofin (Ridaura), are utilized in modern medicine for the treatment of inflammatory arthritis including rheumatoid and juvenile arthritis; however, new gold agents have been slow to enter the clinic. Repurposing of auranofin in different disease indications such as cancer, parasitic, and microbial infections in the clinic has provided impetus for the development of new gold complexes for biomedical applications based on unique mechanistic insights differentiated from auranofin. Various chemical methods for the preparation of physiologically stable gold complexes and associated mechanisms have been explored in biomedicine such as therapeutics or chemical probes. In this Review, we discuss the chemistry of next generation gold drugs, which encompasses oxidation states, geometry, ligands, coordination, and organometallic compounds for infectious diseases, cancer, inflammation, and as tools for chemical biology via gold–protein interactions. We will focus on the development of gold agents in biomedicine within the past decade. The Review provides readers with an accessible overview of the utility, development, and mechanism of action of gold-based small molecules to establish context and basis for the thriving resurgence of gold in medicine.

show abstract

New Auranofin Analogs with Antibacterial Properties against Burkholderia Clinical Isolates

Cited by 6 publications

References 57 publications

Galleria mellonella–intracellular bacteria pathogen infection models: the ins and outs

Galleria mellonella–intracellular bacteria pathogen infection models: the ins and outs

A machine learning model trained on a high-throughput antibacterial screen increases the hit rate of drug discovery

Next Generation Gold Drugs and Probes: Chemistry and Biomedical Applications

Contact Info

Product

Resources

About