The authors wish to make the following corrections to this paper [...].

• Publikační typ
• tisková chyba MeSH

The emergence of antibiotic resistance in opportunistic pathogens represents a huge problem, the solution for which may be a treatment with a combination of multiple antimicrobial agents. Sodium salt of cobalt bis-dicarbollide (COSAN.Na) is one of the very stable, low-toxic, amphiphilic boron-rich sandwich complex heteroboranes. This compound has a wide range of potential applications in the biological sciences due to its antitumor, anti-HIV-1, antimicrobial and antibiofilm activity. Our study confirmed the ability of COSAN.Na (in the concentration range 0.2-2.48 µg/mL) to enhance tetracycline, erythromycin, and vancomycin action towards Staphylococcus epidermidis planktonic growth with an additive or synergistic effect (e.g., the combination of 1.24 µg/mL COSAN.Na and 6.5 µg/mL TET). The effective inhibitory concentration of antibiotics was reduced up to tenfold most efficiently in the case of tetracycline (from 65 to 6.5 µg/mL). In addition, strong effect of COSAN.Na on disruption of the cell envelopes was determined using propidium iodide uptake measurement and further confirmed by transmission electron microscopy. The combination of amphiphilic COSAN.Na with antibiotics can therefore be considered a promising way to overcome antibiotic resistance in Gram-positive cocci.

• Klíčová slova
• Gram-positive bacterium, additive effect, antibiotics, antimicrobial activity, carborane, erythromycin, metallacarboranes, synergistic effect, tetracycline, vancomycin,
• Publikační typ
• časopisecké články MeSH

Fullerene derivatives with hydrophilic substituents have been shown to exhibit a range of biological activities, including antiviral ones. For a long time, the anti-HIV activity of fullerene derivatives was believed to be due to their binding into the hydrophobic pocket of HIV-1 protease, thereby blocking its activity. Recent work, however, brought new evidence of a novel, protease-independent mechanism of fullerene derivatives' action. We studied in more detail the mechanism of the anti-HIV-1 activity of N,N-dimethyl[70]fulleropyrrolidinium iodide fullerene derivatives. By using a combination of in vitro and cell-based approaches, we showed that these C70 derivatives inhibited neither HIV-1 protease nor HIV-1 maturation. Instead, our data indicate effects of fullerene C70 derivatives on viral genomic RNA packaging and HIV-1 cDNA synthesis during reverse transcription-without impairing reverse transcriptase activity though. Molecularly, this could be explained by a strong binding affinity of these fullerene derivatives to HIV-1 nucleocapsid domain, preventing its proper interaction with viral genomic RNA, thereby blocking reverse transcription and HIV-1 infectivity. Moreover, the fullerene derivatives' oxidative activity and fluorescence quenching, which could be one of the reasons for the inconsistency among reported anti-HIV-1 mechanisms, are discussed herein.

• Klíčová slova
• HIV-1, RNA packaging, fullerene, inhibition, nucleocapsid,
• MeSH
• fullereny metabolismus   farmakologie   MeSH
• genom virový účinky léků   MeSH
• genové produkty gag - virus lidské imunodeficience metabolismus   MeSH
• HEK293 buňky MeSH
• HIV-1 účinky léků   genetika   metabolismus   fyziologie   MeSH
• látky proti HIV metabolismus   farmakologie   MeSH
• lidé MeSH
• nukleokapsida - proteiny metabolismus   MeSH
• reverzní transkripce MeSH
• RNA virová metabolismus   MeSH
• svlékání virového obalu účinky léků   MeSH
• vazba proteinů MeSH
• virion metabolismus   MeSH
• zabalení virového genomu účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fullereny MeSH
• genové produkty gag - virus lidské imunodeficience MeSH
• látky proti HIV MeSH
• nukleokapsida - proteiny MeSH
• RNA virová MeSH

Metabolic transformation of cancer cells leads to the accumulation of lactate and significant acidification in the tumor microenvironment. Both lactate and acidosis have a well-documented impact on cancer progression and negative patient prognosis. Here, we report that cancer cells adapted to acidosis are significantly more sensitive to oxidative damage induced by hydrogen peroxide, high-dose ascorbate, and photodynamic therapy. Higher lactate concentrations abrogate the sensitization. Mechanistically, acidosis leads to a drop in antioxidant capacity caused by a compromised supply of nicotinamide adenine dinucleotide phosphate (NADPH) derived from glucose metabolism. However, lactate metabolism in the Krebs cycle restores NADPH supply and antioxidant capacity. CPI-613 (devimistat), an anticancer drug candidate, selectively eradicates the cells adapted to acidosis through inhibition of the Krebs cycle and induction of oxidative stress while completely abrogating the protective effect of lactate. Simultaneous cell treatment with tetracycline, an inhibitor of the mitochondrial proteosynthesis, further enhances the cytotoxic effect of CPI-613 under acidosis and in tumor spheroids. While there have been numerous attempts to treat cancer by neutralizing the pH of the tumor microenvironment, we alternatively suggest considering tumor acidosis as the Achilles' heel of cancer as it enables selective therapeutic induction of lethal oxidative stress.

• Klíčová slova
• CPI-613, acidosis, bioenergetics, cancer, lactate, mitochondria, photodynamic therapy, tetracycline, therapy, tumor microenvironment,
• MeSH
• acidóza patofyziologie   MeSH
• antitumorózní látky farmakologie   MeSH
• citrátový cyklus účinky léků   MeSH
• energetický metabolismus MeSH
• fyziologická adaptace MeSH
• glukosa metabolismus   MeSH
• glykolýza MeSH
• kapryláty farmakologie   MeSH
• koncentrace vodíkových iontů MeSH
• kyselina mléčná metabolismus   MeSH
• lidé MeSH
• mitochondrie účinky léků   metabolismus   patologie   MeSH
• nádorové buňky kultivované MeSH
• nádorové mikroprostředí * MeSH
• nádory farmakoterapie   metabolismus   patologie   MeSH
• oxidační stres MeSH
• sulfidy farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antitumorózní látky MeSH
• devimistat MeSH Prohlížeč
• glukosa MeSH
• kapryláty MeSH
• kyselina mléčná MeSH
• sulfidy MeSH

Due to their bioavailability, glycosylated carotenoids may have interesting biological effects. Sioxanthin, as a representative of this type of carotenoid, has been identified in marine actinomycetes of the genus Salinispora. This study evaluates, for the first time, the effect of cultivation temperature (T) and light intensity (LI) on the total cellular carotenoid content (TC), antioxidant activity (AA) and sioxanthin content (SX) of a crude extract (CE) from Salinispora tropica biomass in its vegetative state. Treatment-related differences in TC and SX values were statistically significantly and positively affected by T and LI, while AA was most significantly affected by T. In the S. tropica CE, TC correlated well (R2 = 0.823) with SX and somewhat less with AA (R2 = 0.777). A correlation between AA and SX was found to be less significant (R2 = 0.731). The most significant protective effect against oxidative stress was identified in the CE extracted from S. tropica biomass grown at the highest T and LI (CE-C), as was demonstrated using LNCaP and KYSE-30 human cell lines. The CE showed no cytotoxicity against LNCaP and KYSE-30 cell lines.

• Klíčová slova
• Salinispora tropica, antioxidant activity, sioxanthin, total cellular carotenoids,
• MeSH
• antioxidancia chemie   farmakologie   MeSH
• bifenylové sloučeniny MeSH
• biomasa MeSH
• buněčné linie účinky léků   MeSH
• karotenoidy metabolismus   farmakologie   MeSH
• komplexní směsi MeSH
• lidé MeSH
• Micromonosporaceae * MeSH
• mycelium MeSH
• oxidační stres účinky léků   MeSH
• pikráty MeSH
• světlo MeSH
• teplota MeSH
• vodní organismy MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 1,1-diphenyl-2-picrylhydrazyl MeSH Prohlížeč
• antioxidancia MeSH
• bifenylové sloučeniny MeSH
• karotenoidy MeSH
• komplexní směsi MeSH
• pikráty MeSH
• sioxanthin MeSH Prohlížeč

Betulinic acid (BA) is a potent triterpene, which has shown promising potential in cancer and HIV-1 treatment. Here, we report a synthesis and biological evaluation of 17 new compounds, including BODIPY labelled analogues derived from BA. The analogues terminated by amino moiety showed increased cytotoxicity (e.g., BA had on CCRF-CEM IC50 > 50 μM, amine 3 IC50 0.21 and amine 14 IC50 0.29). The cell-cycle arrest was evaluated and did not show general features for all the tested compounds. A fluorescence microscopy study of six derivatives revealed that only 4 and 6 were detected in living cells. These compounds were colocalized with the endoplasmic reticulum and mitochondria, indicating possible targets in these organelles. The study of anti-HIV-1 activity showed that 8, 10, 16, 17 and 18 have had IC50i > 10 μM. Only completely processed p24 CA was identified in the viruses formed in the presence of compounds 4 and 12. In the cases of 2, 8, 9, 10, 16, 17 and 18, we identified not fully processed p24 CA and p25 CA-SP1 protein. This observation suggests a similar mechanism of inhibition as described for bevirimat.

• Klíčová slova
• BODIPY, betulinic acid, bevirimat, cancer, cell-cycle, cytotoxicity, fluorescent microscopy, maturation inhibitor,
• Publikační typ
• časopisecké články MeSH