Novel Antimicrobial 8-Hydroxyquinoline-Based Agents: Current Development, Structure–Activity Relationships, and Perspectives

Joaquim, Angélica Rocha; Gionbelli, Mariana Pies; Gosmann, Grace; Fuentefría, Alexandre Meneghello; Lopes, Marcela Silva; Andrade, Saulo Fernandes de

doi:10.1021/acs.jmedchem.1c01318

Cited by 48 publications

(25 citation statements)

References 141 publications

(343 reference statements)

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“…Nitroxoline (5-nitro-8-hydroxyquinoline, NIT) is a heterocyclic aromatic compound from a family of 8-hydroxyquinoline (8-HQ, or oxine) derivatives, a group of compounds with an extremely broad spectrum of pharmacological [ 16 , 20 , 22 , 35 , 75 , 76 ] and non-pharmacological [ 77 , 78 , 79 ] applications. NIT does not belong to any typical class of antibacterials, and it is best known as an effective uroantiseptic that shows no pronounced toxic side effects [ 16 , 19 , 80 , 81 ].…”

Section: Nitroxolinementioning

confidence: 99%

“…Its use dates back to the beginning of the 20th century [ 82 , 83 ], but is currently becoming an option for the treatment of infections caused by multidrug-resistant uropathogens, primarily due to an increase of the bacterial resistance to more commonly used antibacterials and its unique MOA [ 10 , 13 , 20 ]. Out of all classes of antibacterials, 8-HQ derivatives are the only ones currently in use whose antibacterial actions, and bioactivity in general, rest almost exclusively on their chelation properties [ 31 , 35 , 79 , 82 , 84 ]. Chelation is also responsible for NIT’s unique ability to inhibit the formation of bacterial biofilm (i.e., biofilm activity) [ 12 , 18 ], as explained in the following paragraph.…”

Section: Nitroxolinementioning

confidence: 99%

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Chelation in Antibacterial Drugs: From Nitroxoline to Cefiderocol and Beyond

et al. 2022

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In the era of escalating antimicrobial resistance, the need for antibacterial drugs with novel or improved modes of action (MOAs) is a health concern of utmost importance. Adding or improving the chelating abilities of existing drugs or finding new, nature-inspired chelating agents seems to be one of the major ways to ensure progress. This review article provides insight into the modes of action of antibacterial agents, class by class, through the perspective of chelation. We covered a wide scope of antibacterials, from a century-old quintessential chelating agent nitroxoline, currently unearthed due to its newly discovered anticancer and antibiofilm activities, over the commonly used antibacterial classes, to new cephalosporin cefiderocol and a potential future class of tetramates. We show the impressive spectrum of roles that chelation plays in antibacterial MOAs. This, by itself, demonstrates the importance of understanding the fundamental chemistry behind such complex processes.

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Section: Nitroxolinementioning

confidence: 99%

Section: Nitroxolinementioning

confidence: 99%

Chelation in Antibacterial Drugs: From Nitroxoline to Cefiderocol and Beyond

et al. 2022

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“…8-Hydroxyquinoline (8HQ) presents an excellent ability to bind diverse metal ions and has been used in their gravimetric analysis and separation [ 6 ]. Additionally, it is considered a privileged structure for drug development due to its numerous reported biological activities [ 7 , 8 , 9 , 10 ]. Our hypothesis is that extending the coordination ability of 8HQ by attaching additional donor groups adjacent to the quinoline nitrogen will modify the properties of the metal-based complexes, increasing their stability and activity by the assembly of different bioactive organic moieties.…”

Section: Introductionmentioning

confidence: 99%

Liposomal Formulations of a New Zinc(II) Complex Exhibiting High Therapeutic Potential in a Murine Colon Cancer Model

Ribeiro

Albino

Ferreira

et al. 2022

IJMS

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Colorectal cancer is the second leading cause of cancer-related mortality. Many current therapies rely on chemotherapeutic agents with poor specificity for tumor cells. The clinical success of cisplatin has prompted the research and design of a huge number of metal-based complexes as potential chemotherapeutic agents. In this study, two zinc(II) complexes, [ZnL2] and [ZnL(AcO)], where AcO is acetate and L is an organic compound combining 8-hydroxyquinoline and a benzothiazole moiety, were developed and characterized. Analytical and spectroscopic studies, namely, NMR, FTIR, and UV-Vis allowed us to establish the complexes’ structures, demonstrating the ligand-binding versatility: tetradentate in [ZnL(AcO)] and bidentate in [ZnL2]. Complexes were screened in vitro using murine and human colon cancer cells cultured in 2D and 3D settings. In 2D cells, the IC50 values were <22 µM, while in 3D settings, much higher concentrations were required. [ZnL(AcO)] displayed more suitable antiproliferative properties than [ZnL2] and was chosen for further studies. Moreover, based on the weak selectivity of the zinc-based complex towards cancer cell lines in comparison to the non-tumorigenic cell line, its incorporation in long-blood-circulating liposomes was performed, aiming to improve its targetability. The resultant optimized liposomal nanoformulation presented an I.E. of 76% with a mean size under 130 nm and a neutral surface charge and released the metal complex in a pH-dependent manner. The antiproliferative properties of [ZnL(AcO)] were maintained after liposomal incorporation. Preliminary safety assays were carried out through hemolytic activity that never surpassed 2% for the free and liposomal forms of [ZnL(AcO)]. Finally, in a syngeneic murine colon cancer mouse model, while free [ZnL(AcO)] was not able to impair tumor progression, the respective liposomal nanoformulation was able to reduce the relative tumor volume in the same manner as the positive control 5-fluorouracil but, most importantly, using a dosage that was 3-fold lower. Overall, our results show that liposomes were able to solve the solubility issues of the new metal-based complex and target it to tumor sites.

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“…The other approach we used was the incorporation of chemical compounds with strong antimicrobial and antifungal activity into the fibrous materials. For instance, 8hydroxyquinoline and its derivatives belong to a group of chemical fungicides and possess antimicrobial [26,27], antiviral [28] and antifungal properties [29,30].…”

Section: Introductionmentioning

confidence: 99%

Eco-Friendly Hybrid PLLA/Chitosan/Trichoderma asperellum Nanomaterials as Biocontrol Dressings against Esca Disease in Grapevines

et al. 2022

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Fungi constitute the largest number of plant pathogens and are responsible for a range of serious plant diseases. Phaeomoniella chlamydospora (P. chlamydospora) and Phaeoacremonium aleophilum (P. aleophilum) are the main fungal pathogens causing esca disease in grapevines. On the other hand, there are beneficial microorganisms such as Trichoderma spp., which are able to control the growth of many phytopathogens. In the present study, innovative, eco-friendly hybrid nanomaterials were created by electrospinning PLLA, followed by the formation of a film of chitosan/Trichoderma asperellum (T. asperellum) spores on the fibers. The polymer carrier used in this study plays an active role in ensuring the viability of the biological agent during storage and, when placed in contact with moisture, ensures the agent’s normal development. Oligochitosan, as well as low molecular weight and high molecular weight chitosan, were used. The effects of chitosan molecular weight on the dynamic viscosity of chitosan solutions, film formation, mechanical properties, spore incorporation and growth were studied. The morphology of the prepared nanomaterials, and the presence of a film based on the formation of chitosan/T. asperellum spores on the PLLA fibers, were examined using scanning electron microscopy (SEM). The surface chemical compositions of the fibrous materials were studied using attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR). The mechanical properties of the obtained materials were also tested. The microbiological screening that was performed revealed that the eco-friendly hybrid nanomaterials incorporated with the beneficial microorganism, T. asperellum, to hamper the growth of the pathogenic P. chlamydospora and P. aleophilum fungi. The suppression rate depended on the viscosity of the chitosan solution used for the film formation. The use of oligochitosan resulted in the most effective infection of the material with T. asperellum spores. The environmentally friendly hybrid nanomaterials obtained in this study—in which the bioagent was embedded—are promising bioactive dressings for protecting grapevines against esca disease.

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Novel Antimicrobial 8-Hydroxyquinoline-Based Agents: Current Development, Structure–Activity Relationships, and Perspectives

Cited by 48 publications

References 141 publications

Chelation in Antibacterial Drugs: From Nitroxoline to Cefiderocol and Beyond

Chelation in Antibacterial Drugs: From Nitroxoline to Cefiderocol and Beyond

Liposomal Formulations of a New Zinc(II) Complex Exhibiting High Therapeutic Potential in a Murine Colon Cancer Model

Eco-Friendly Hybrid PLLA/Chitosan/Trichoderma asperellum Nanomaterials as Biocontrol Dressings against Esca Disease in Grapevines

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