Dehydroepiandrosterone derived imidazolium salts and their antimicrobial efficacy

Hryniewicka, Agnieszka; Niemirowicz-Laskowska, Katarzyna; Wielgat, Przemysław; Car, Halina; Hauschild, Tomasz; Morzycki, Jacek W.

doi:10.1016/j.bioorg.2020.104550

Cited by 8 publications

(20 citation statements)

References 73 publications

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“…In sharp contrast, almost all imidazolium salts ( R 1 IR 2 ) exhibited a stronger antibacterial effect, including against ESBL-EC and MRSA ( p > 2.4). The antibacterial efficiency of R 1 IR 2 is quite similar to that of dehydroepiandrosterone-derived ( Hryniewicka et al, 2021 ), peptide-conjugated ( Reinhardt et al, 2014 ), ethoxyether-functionalized ( Huang et al, 2011 ), amino acid–derived ( Valls et al, 2020 ), polydiacetylene-conjugated ( Lee et al, 2016 ), and unsymmetrically substituted ( Çoban et al, 2017 ; Duman et al, 2019 ) imidazolium salts in previous reports. Furthermore, the antibacterial activity of imidazolium salts ( R 1 IR 2 ) increased following the substitution of methyl and bromobenzyl with dibromobenzyl groups and the change from one to two dibromobenzyl groups ( Table 3 ).…”

Section: Resultssupporting

confidence: 80%

Hypochlorite-Activated Fluorescence Emission and Antibacterial Activities of Imidazole Derivatives for Biological Applications

et al. 2021

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The ability to detect hypochlorite (HOCl/ClO−) in vivo is of great importance to identify and visualize infection. Here, we report the use of imidazoline-2-thione (R1SR2) probes, which act to both sense ClO− and kill bacteria. The N2C=S moieties can recognize ClO− among various typical reactive oxygen species (ROS) and turn into imidazolium moieties (R1IR2) via desulfurization. This was observed through UV–vis absorption and fluorescence emission spectroscopy, with a high fluorescence emission quantum yield (ՓF = 43–99%) and large Stokes shift (∆v∼115 nm). Furthermore, the DIM probe, which was prepared by treating the DSM probe with ClO−, also displayed antibacterial efficacy toward not only Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) but also methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum ß-lactamase–producing Escherichia coli (ESBL-EC), that is, antibiotic-resistant bacteria. These results suggest that the DSM probe has great potential to carry out the dual roles of a fluorogenic probe and killer of bacteria.

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Section: Resultssupporting

confidence: 80%

Hypochlorite-Activated Fluorescence Emission and Antibacterial Activities of Imidazole Derivatives for Biological Applications

et al. 2021

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“…However, the occurrence of pyroptosis also has application value, which is reflected in the fact that pyroptosis can act an important role in anti-infection immunity [ 58 ] and anti-tumor immunity [ 59 ]. In fact, the current study may also provide a partial explanation that why DHEA has the ability to resist foreign microbial infection [ 60 – 63 ] while it also has anti-inflammatory function [ 19 , 21 , 64 ]. Of course, the fine regulation mechanism of DHEA on the pyroptosis is still a research worthy of further exploration.…”

Section: Discussionmentioning

confidence: 99%

Dehydroepiandrosterone exacerbates nigericin-induced abnormal autophagy and pyroptosis via GPER activation in LPS-primed macrophages

Cao

Yao

et al. 2022

Cell Death Dis

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As a widely acknowledged FDA-approved dietary supplement or over-the-counter medicines, dehydroepiandrosterone (DHEA) exerts anti-inflammatory and immunomodulatory function. Pyroptosis is an important form of programmed cell death (PCD), and which acts a key role in the body’s anti-infection and inflammatory responses. But the effects and mechanisms of DHEA on pyroptosis remain unclear. Here, we found that DHEA inhibited the NLRP3 inflammasome components expression by blocking inflammatory signals in lipopolysaccharide (LPS)-primed macrophages, and prevented the bacterial toxin nigericin (Nig)-induced NLRP3 inflammasome assembly. However, DHEA exacerbated NLRP3-independent cell death in Nig-treated inflammatory macrophages. During this process, DHEA induced the abnormal autophagy, which reflected as the blocking of autophagic flux and the accumulation of autophagy receptor p62 (SQSTM1) protein. In addition, DHEA caused a burst of reactive oxygen species (ROS) and activated extracellular signal-regulated kinase (ERK) phosphorylation in LPS plus Nig-stimulated macrophages but not in LPS-treated macrophages. Mechanistically, the present study certified that the activation of G protein-coupled estrogen receptor (GPER) signal mediated the cell death induced by DHEA in Nig-stimulated inflammatory macrophages, as GPER specific inhibitor G15 alleviated the abnormal autophagy and ultimately prevented the gasdermin D (GSDMD)-mediated pyroptosis induced by DHEA. Collectively, DHEA can exacerbate Nig-induced abnormal autophagy and pyroptosis via activation of GPER in LPS-primed macrophages, which prompts us the potential application value of DHEA in anti-infection or anti-tumor immunity.

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“…In the present research, the highest antifungal activity is shown by lithocholic-based salts with 1-6 carbon atoms in the alkyl substituent (3a-f, except 3c and 3d, against A. niger and T. mentagrophytes). The highest activity is revealed by salt 3b, which is the best candidate for In our previous study on dehydroepiandrosterone-derived imidazolium salts, we suggested that the 'side chain effect' may be crucial in the observed antimicrobial activity of synthesized hybrids [36]. A strong antimicrobial efficacy was observed when compounds have alkyl chain lengths greater than four and lower than twelve carbon atoms.…”

Section: Antimicrobial Studiesmentioning

confidence: 92%

“…This trend is the most visible for E. coli, where the salts with 12 and 16 carbon atoms (3i-j, and 4i-j) were inactive. In our previous study on dehydroepiandrosterone-derived imidazolium salts, we suggested that the 'side chain effect' may be crucial in the observed antimicrobial activity of synthesized hybrids [36]. A strong antimicrobial efficacy was observed when compounds have alkyl chain lengths greater than four and lower than twelve carbon atoms.…”

Section: Antimicrobial Studiesmentioning

confidence: 97%

Steroid-Functionalized Imidazolium Salts with an Extended Spectrum of Antifungal and Antibacterial Activity

Malinowska

Sawicka

Niemirowicz-Laskowska

et al. 2021

IJMS

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It is established that high rates of morbidity and mortality caused by fungal infections are related to the current limited number of antifungal drugs and the toxicity of these agents. Imidazolium salts as azole derivatives can be successfully used in the treatment of fungal infections in humans. Steroid-functionalized imidazolium salts were synthesized using a new, more efficient method. As a result, 20 salts were obtained with high yields, 12 of which were synthesized and characterized for the first time. They were derivatives of lithocholic acid and 3-oxo-23,24-dinorchol-4-ene-22-al and were fully characterized by 1H and 13C nuclear magnetic resonance (NMR), infrared spectroscopy (IR), and high resolution mass spectrometry (HRMS). Due to the excellent activity against bacteria and Candida albicans, new research was extended to include tests on five species of pathogenic fungi and molds: Aspergillus niger ATCC 16888, Aspergillus fumigatus ATCC 204305, Trichophyton mentagrophytes ATCC 9533, Cryptococcus neoformans ATCC 14116, and Microsporum canis ATCC 11621. The results showed that the new salts are almost universal antifungal agents and have a broad spectrum of activity against other human pathogens. To initially assess the safety of the synthesized salts, hemocompatibility with host cells and cytotoxicity were also examined. No toxicity was observed at the concentration at which the compounds were active against pathogens.

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Dehydroepiandrosterone derived imidazolium salts and their antimicrobial efficacy

Cited by 8 publications

References 73 publications

Hypochlorite-Activated Fluorescence Emission and Antibacterial Activities of Imidazole Derivatives for Biological Applications

Hypochlorite-Activated Fluorescence Emission and Antibacterial Activities of Imidazole Derivatives for Biological Applications

Dehydroepiandrosterone exacerbates nigericin-induced abnormal autophagy and pyroptosis via GPER activation in LPS-primed macrophages

Steroid-Functionalized Imidazolium Salts with an Extended Spectrum of Antifungal and Antibacterial Activity

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