Mechanism of action of an old antibiotic revisited: Role of calcium ions in protonophoric activity of usnic acid

Antonenko, Yuri N.; Khailova, Ljudmila S.; Rokitskaya, Tatyana I.; Nosikova, Ekaterina S.; Nazarov, Pavel A.; Luzina, O. A.; Salakhutdinov, N. F.; Kotova, Еlena А.

doi:10.1016/j.bbabio.2019.01.005

Cited by 32 publications

(34 citation statements)

References 35 publications

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“…Mitochondria were isolated from rat liver by using differential centrifugation [28], according to a slightly modified procedure previously described [29]. The animals were handled and the experiments were performed in accordance with the international guidelines for animal care and use and the Institutional Ethics Committee of A.N.…”

Section: Isolation Of Rat Liver Mitochondriamentioning

confidence: 99%

“…The respiration of isolated rat liver mitochondria (RLM) was measured at the mitochondrial protein concentration of 0.8 mg/mL by using a Clark-type oxygen electrode (Strathkelvin Instruments, Motherwell, UK), as described previously [29].…”

Section: Measurement Of Mitochondrial Membrane Potential and Respirationmentioning

confidence: 99%

“…The mitochondrial membrane potential ∆Ψ was evaluated from the difference in the absorbance at 555 and 523 nm (∆A) of the safranine O dye [30], measured with an Aminco DW-2000 spectrophotometer, as described previously [29]. Mitochondria were incubated in medium containing 250 mM sucrose, 5 mM MOPS, 0.5 mM KH 2 PO 4 , 1 mM EGTA, 2 µM rotenone, 5 mM succinate (pH 7.4), 1 µg/mL oligomycin, and 15 µM safranine O at the mitochondrial protein content of 0.6-0.9 mg protein/mL.…”

Section: Measurement Of Mitochondrial Membrane Potential and Respirationmentioning

confidence: 99%

“…The fluorescence correlation spectroscopy (FCS) measurements were carried out with a homemade FCS setup [29,39] including an Olympus IMT-2 inverted microscope with a 40x, NA 1.2 water immersion objective (Carl Zeiss, Jena, Germany). A Nd:YAG solid state laser was used for excitation.…”

Section: Fluorescence Correlation Spectroscopymentioning

confidence: 99%

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Fluorescein Derivatives as Antibacterial Agents Acting via Membrane Depolarization

et al. 2020

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Appending a lipophylic alkyl chain by ester bond to fluorescein has been previously shown to convert this popular dye into an effective protonophoric uncoupler of oxidative phosphorylation in mitochondria, exhibiting neuro- and nephroprotective effects in murine models. In line with this finding, we here report data on the pronounced depolarizing effect of a series of fluorescein decyl esters on bacterial cells. The binding of the fluorescein derivatives to Bacillus subtilis cells was monitored by fluorescence microscopy and fluorescence correlation spectroscopy (FCS). FCS revealed the energy-dependent accumulation of the fluorescein esters with decyl(triphenyl)- and decyl(tri-p-tolyl)phosphonium cations in the bacterial cells. The latter compound proved to be the most potent in suppressing B. subtilis growth.

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Section: Isolation Of Rat Liver Mitochondriamentioning

confidence: 99%

Section: Measurement Of Mitochondrial Membrane Potential and Respirationmentioning

confidence: 99%

Section: Measurement Of Mitochondrial Membrane Potential and Respirationmentioning

confidence: 99%

Section: Fluorescence Correlation Spectroscopymentioning

confidence: 99%

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Fluorescein Derivatives as Antibacterial Agents Acting via Membrane Depolarization

et al. 2020

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“…Dissipation of the proton gradient across the inner mitochondrial membrane disrupts coupling between electron transport and ATP synthesis and is thought to play a major role in UA cytotoxicity [6]. Mitochondrial impairment, such as a drop in mitochondrial membrane potential, oxidative phosphorylation inhibition, ROS production, swelling, drop in ATP level and adaptive overexpression of genes associated with the electron transport chain, the Krebs cycle and lipid metabolism, have been shown to occur in the in vivo and/or in vitro models (cultured hepatocytes or cancer cells), as well as in isolated mitochondria [6,7,11,[13][14][15][16][17]. Such events lead to mitochondrial pathway of apoptosis [18][19][20][21][22], necrosis [15] and autophagy [14, 18, 23••].…”

Section: Introductionmentioning

confidence: 99%

Usnic Acid Derivatives as Cytotoxic Agents Against Cancer Cells and the Mechanisms of Their Activity

2019

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Purpose of Review This article summarises recent research on modifications of the structure or formula of usnic acid (UA), a lichen secondary metabolite, in order to obtain derivatives with higher bioavailability, potency and selectivity against cancer cells and presents the current knowledge on the mechanisms of action of such compounds. Recent Findings Numerous approaches have been undertaken to improve bioactivity of UA concerning its use as an anticancer drug. Among them, the synthesis of UA salts or complexation with 2-hydroxypropyl-β-cyclodextrin to improve its solubility and the encapsulation using different carriers (including various nanomaterials) to stabilise UA in biological fluids and improve their penetrance to, and release in, cancer cells were applied.. Synthetic modification of the UA structure has been explored to obtain more active and cancer-specific derivatives. Recent work indicates that some modifications of the C or A ring of UA selectively increase its antiproliferative potential against cancer cells. Moreover, specific changes in the UA structure allow to obtain derivatives which inhibit enzymes important for the cancer cells' survival, such as mTOR, Pim, TDP1 or PARP. Some of them have been shown to enhance anticancer activity of the already approved chemotherapeutics, such as topotecan. Others, when used in an animal cancer xenograft model, were superior to UA in retardation of tumour growth and less toxic that the parent compound. Summary UA is a promising lead compound for synthesis of anticancer drugs. Further work on its modifications, mechanisms of activity and validation in animal models is critical for development of effective therapeutics.

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Usnic‐Acid‐Functionalized Silk Fibroin Composite Scaffolds for Cutaneous Wounds Healing

Zha

Xiong

Chen

et al. 2020

Macromolecular Bioscience

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Despite the progress in chronic wound treatment, antibacterial cutaneous scaffold with high efficiency in wound healing is still the hot spot in the field. In present study, a functionalized silk fibroin (SF) cutaneous scaffold incorporated with natural medicine usnic acid (UA) is investigated, in which UA is used as an antibacterial and wound‐healing reagent. Via electrospinning, UA–SF mixture is fabricated into UA–SF composite scaffold (USCS), which is composed of uniform nanofibers with average diameters of around 360 ± 10 nm. The interwoven nanofibers form mesh structure providing sufficient moisture permeability for scaffold. With methanol treatment, USCS presents improved mechanical properties and stability to protease XIV. In the presence of USCS, the growth rate of both Gram‐positive and Gram‐negative bacteria, including Staphylococcus aureus, Streptococci pyogenes, Escherichia coli, and Pseudomonas aeruginosa, is significantly inhibited in plate culture and suspension assays. In a cutaneous excisional mouse wound model, USCS presents a significant increase of wound closure rate, compared with pure SF scaffold and commercial dressing, Tegaderm Hydrocolloid 3M. The histological assessments further prove that USCS can enhance re‐epithelialization, vascularization, and collagen deposition in wound site to promote the wound‐healing process, which indicates the potential application of USCS in chronic wound treatment.

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Mechanism of action of an old antibiotic revisited: Role of calcium ions in protonophoric activity of usnic acid

Cited by 32 publications

References 35 publications

Fluorescein Derivatives as Antibacterial Agents Acting via Membrane Depolarization

Fluorescein Derivatives as Antibacterial Agents Acting via Membrane Depolarization

Usnic Acid Derivatives as Cytotoxic Agents Against Cancer Cells and the Mechanisms of Their Activity

Usnic‐Acid‐Functionalized Silk Fibroin Composite Scaffolds for Cutaneous Wounds Healing

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