76835-64-8Relevant articles and documents
Profiling structural diversity and activity of 2-alkyl-4(1H)-quinoloneN-oxides ofPseudomonasandBurkholderia
B?ttcher, Thomas,Dieterich, Cora Lisbeth,Prothiwa, Michaela,Szamosvári, Dávid
supporting information, p. 6328 - 6331 (2020/06/21)
We synthesized all major saturated and unsaturated 2-alkyl-4(1H)-quinoloneN-oxides ofPseudomonasandBurkholderia, quantified their native production levels and characterized their antibiotic activities against competingStaphylococcus aureus. We demonstrate that quinolone core methylation and position of unsaturation in the alkyl-chain dictate antibiotic potency which supports the proposed mechanism of action.
Quinolones modulate ghrelin receptor signaling: Potential for a novel small molecule scaffold in the treatment of cachexia
Torres-Fuentes, Cristina,Pastor-Cavada, Elena,Cano, Rafael,Kandil, Dalia,Shanahan, Rachel,Juan, Rocio,Shaban, Hamdy,McGlacken, Gerard P.,Schellekens, Harri?t
, (2018/06/07)
Cachexia is a metabolic wasting disorder characterized by progressive weight loss, muscle atrophy, fatigue, weakness, and appetite loss. Cachexia is associated with almost all major chronic illnesses including cancer, heart failure, obstructive pulmonary disease, and kidney disease and significantly impedes treatment outcome and therapy tolerance, reducing physical function and increasing mortality. Current cachexia treatments are limited and new pharmacological strategies are needed. Agonists for the growth hormone secretagogue (GHS-R1a), or ghrelin receptor, prospectively regulate the central regulation of appetite and growth hormone secretion, and therefore have tremendous potential as cachexia therapeutics. Non-peptide GHS-R1a agonists are of particular interest, especially given the high gastrointestinal degradation of peptide-based structures, including that of the endogenous ligand, ghrelin, which has a half-life of only 30 min. However, few compounds have been reported in the literature as non-peptide GHS-R1a agonists. In this paper, we investigate the in vitro potential of quinolone compounds to modulate the GHS-R1a in both transfected human cells and mouse hypothalamic cells. These chemically synthesized compounds demonstrate a promising potential as GHS-R1a agonists, shown by an increased intracellular calcium influx. Further studies are now warranted to substantiate and exploit the potential of these novel quinolone-based compounds as orexigenic therapeutics in conditions of cachexia and other metabolic and eating disorders.
Exploiting interkingdom interactions for development of small-molecule inhibitors of candida albicans biofilm formation
Reen, F. Jerry,Phelan, John P.,Gallagher, Lorna,Woods, David F.,Shanahan, Rachel M.,Cano, Rafael,Muimhneacháin, Eoin ó,McGlacken, Gerard P.,O'Gara, Fergal
supporting information, p. 5894 - 5905 (2016/11/06)
A rapid decline in the development of new antimicrobial therapeutics has coincided with the emergence of new and more aggressive multidrug-resistant pathogens. Pathogens are protected from antibiotic activity by their ability to enter an aggregative biofilm state. Therefore, disrupting this process in pathogens is a key strategy for the development of next-generation antimicrobials. Here, we present a suite of compounds, based on the Pseudomonas aeruginosa 2-heptyl-4(1H)-quinolone (HHQ) core quinolone interkingdom signal structure, that exhibit noncytotoxic antibiofilm activity toward the fungal pathogen Candida albicans. In addition to providing new insights into what is a clinically important bacterium-fungus interaction, the capacity to modularize the functionality of the quinolone signals is an important advance in harnessing the therapeutic potential of signaling molecules in general. This provides a platform for the development of potent next-generation small-molecule therapeutics targeting clinically relevant fungal pathogens.
