Attila Ványolós

Significant activity of ecdysteroids on the resistance to doxorubicin in mammalian cancer cells expressing the human ABCB1 transporter.

Multidrug resistance (MDR) is a major cause of failure of cancer chemotherapy. Fifty-eight ecdysteroids, herbal analogues of the insect molting hormone and their semisynthetic derivatives, were tested for their activity against L5178 mouse T-cell lymphoma cells (non-MDR) and their subcell line transfected with pHa MDR1/A retrovirus overexpressing the human ABCB1 efflux pump (MDR cell line). The compounds showed very low antiproliferative activities but modulated the efflux of rhodamine 123 mediated by the ABCB1 transporter. Roughly depending on the polarity, mild to strong synergism or antagonism was observed by combining ecdysteroids with doxorubicin, and specific structure-activity relationships were also found. Our results show the effect of ecdysteroids on MDR cancer cells for the first time. Less polar derivatives may serve as valuable leads toward a potent and safe resistance modulator. Biological significance of the resistance-increasing activity of the most abundant phytoecdysteroids including 20-hydroxyecdysone is yet to be clarified.

C-29 ecdysteroids from Ajuga reptans var. reptans

Investigation of the ecdysteroid constituents of the herb Ajuga reptans var. reptans resulted in the isolation of three new ecdysteroids, named reptanslactone A (2), reptanslactone B (3), and sendreisterone (5), and the known 24-dehydroprecyasterone (1) and breviflorasterone (4). The structures of compounds 1-5 were determined by spectroscopic methods including one- and two-dimensional NMR measurements.

Gymnopeptides A and B, Cyclic Octadecapeptides from the Mushroom Gymnopus fusipes

Mycochemical study of the mushroom Gymnopus fusipes led to the discovery of two new cyclopeptides. The two compounds, named as gymnopeptides A and B, are unprecedented highly N-methylated cyclic octadecapeptides. Detailed spectroscopic studies, Marfeys analysis, and a preliminary molecular modeling study suggested that both are natural cyclic β hairpins. The isolated compounds exhibited striking antiproliferative activity on several human cancer cell lines, with nanomolar IC50 values.

Ecdysteroids from Polypodium vulgare L.

Three new compounds (3, 7, and 11) together with eight known phytoecdysteroids (1, 2, 4-6, and 8-10) were isolated from the rhizomes of common polypody, Polypodium vulgare L. The structures of compounds were elucidated by spectroscopic methods including 1D and 2D NMR measurements. The (1)H and (13)C NMR assignments of compounds 1, 6, 9 and 10 are included.

Xanthine oxidase inhibitory activity of hungarian wild-growing mushrooms

Mushrooms represent a remarkable and yet largely unexplored source of new, biologically active natural products. In this work, we report on the xanthine oxidase (XO) inhibitory activity of 47 wild‐growing mushrooms native to Hungary. Aqueous and organic (n‐hexane, chloroform, and 50% methanol) extracts of selected mushrooms from different families were screened for their XO inhibitory activities. Among the 188 extracts investigated, the chloroform and 50% methanol fractions proved to be the most effective. Some species exhibited high inhibitory activity, e.g., Hypholoma fasciculare (IC50 = 67.76 ± 11.05 µg/mL), Suillus grevillei (IC50 = 13.28 ± 1.58 µg/mL), and Tricholoma populinum (IC50 = 85.08 ± 15.02 µg/mL); others demonstrated moderate or weak activity. Additional studies are warranted to characterize the compounds responsible for the XO inhibitory activity of mushroom extracts. Copyright

Novel Ecdysteroids from Serratula wolffii

Two new and one known ecdysteroids were identified in the methanolic extract of the roots of Serratula wolffii. The new compounds isolated were ponasterone A-22-apioside (1) and 3-epi-shidasterone (3), together with the known 3-epi-22-deoxy-20-hydroxyecdysone (2). The structures of compounds 1–3 were determined by extensive spectroscopic techniques, including one- and two-dimensional NMR methods.

Investigation of Hungarian mushrooms for antibacterial activity and synergistic effects with standard antibiotics against resistant bacterial strains.

This study aimed to screen the antibacterial activity of 160 extracts of 40 mushroom species, collected in Hungary, against 11 standard bacterial strains and 9 clinical isolates. The further objective of this work was to evaluate the capacity of active fungal extracts to potentiate the action of antibiotics against resistant pathogens. Disc‐diffusion method was applied for screening of antibacterial activity of extracts. Microdilution method was used to determine minimum inhibitory concentrations. The active extracts were applied to different resistant micro‐organisms (multiresistant Acinetobacter baumannii and Pseudomonas aeruginosa, vancomycin‐resistant Enterococcus faecium and MRSA), combined with commercial drugs. The synergism between extracts and antibiotics was assessed by double‐disc synergy assay and determination of fractional inhibitory concentration (FIC) with checkerboard technique. From 40 mushrooms included in this experiment, 16 species exhibited antibacterial effects with moderate to high potential. In general the chloroform extracts proved to be most active, while the aqueous and aqueous‐methanolic extracts demonstrated low or no activity. Fistulina hepatica, Tapinella atrotomentosa (syn. Paxillus atrotomentosus) and Rhodocybe popinalis were the most active species; moreover, they can potentiate the action of cefuroxime against MRSA.

Bioactivity-Guided isolation of antimicrobial and antioxidant metabolites from the mushroom tapinella atrotomentosa

Bioassay-guided fractionation of the chloroform extract of Tapinella atrotomentosa led to the isolation of four secondary metabolites 1–4. Two of the compounds are lactones—osmundalactone (1) and 5-hydroxy-hex-2-en-4-olide (2)—while 3 and 4 were identified as terphenyl quinones, spiromentins C and B, respectively. The structures of the compounds were established on the basis of NMR and MS spectroscopic analysis. The isolated fungal metabolites were evaluated for their antibacterial activities against several Gram-positive and negative bacteria. In addition, their synergistic effect with cefuroxime against methicillin-resistant Staphylococcus aureus (MRSA) was also evaluated. Compounds 1–3 proved to possess significant antibacterial activity against multiresistant Acinetobacter baumannii and extended-spectrum β-lactamase (ESBL)-producing Escherichia coli. The investigation of the antioxidant effect of the isolated compounds in DPPH and ORAC assays revealed that spiromentins C (3) and B (4) have remarkable antioxidant activity.

Az óriás likacsosgomba (Meripilus giganteus Karst.) tartalomanyagainak vizsgálata

Az óriás likacsosgomba (Meripilus giganteus) a Meripilaceae család hazánkban legelterjedtebb tagja. A faj leginkább bükkösökben fordul elő, parazita vagy szaprofita életmódot folytat. Bár fiatalon ehető, nem ízletes, emiatt nem széleskörűen gyűjtött gomba. Korábbi farmakológiai vizsgálatok eredményei alapján az óriás likacsosgomba kivonata antibakteriális és antioxidáns hatással rendelkezik, azonban a tapasztalt hatásért felelős tartalomanyagokról igen kevés információval rendelkezünk. Munkánk célja volt az óriás likacsosgomba biológiailag aktív vegyületeinek izolálása, szerkezetmeghatározása és farmakológiai hatásának vizsgálata. A vizsgálandó mintát több észak-magyarországi lelőhelyen gyűjtöttük 2016 őszén. A 12 kg gombát szobahőmérsékleten metanollal kivontuk, majd n-hexánnal, ill. kloroformmal folyadék-folyadék extrakciót végeztünk. Ezt követően a kloroformos frakcióból különböző elválasztástechnikai módszerek alkalmazásával (flash kromatográfia, normál és fordított fázisú HPLC, preparatív rétegkromatográfia) 6 komponenst izoláltuk, amelyek szerkezet-meghatározása spektroszkópiai módszerek (NMR és MS) segítségével történt. Az azonosított összetevők között ergosztán vázas és ceramid típusú vegyületeket, illetve hidroxi-zsírsavakat is találtunk. A komponensek antioxidáns hatását ORAC és DPPH módszerekkel vizsgáltuk. Munkánk folytatásaként a vegyületek antibakteriális hatásának vizsgálatát és a hexános frakció jellegzetes komponenseinek azonosítását tervezzük.