Mirosław Anioł

Isoxanthohumol--Biologically active hop flavonoid.

Isoxanthohumol (IXN), apart from xanthohumol (XN) and 8-prenylnaringenin (8PN), is one of the most important prenylflavonoids found in hops. Another natural source of this compound is a shrub Sophora flavescens, used in traditional Chinese medicine. Main dietary source of IXN is beer, and the compound is produced from XN during wort boiling. In the human body, the compound is O-demethylated to 8PN, the strongest known phytoestrogen. This process takes place in the liver and in the intestine, where it is mediated by local microflora. It has been reported in some studies that even though beer contains small amounts of hops and its preparations, these compounds may affect the functioning of the human body. IXN exhibits an antiproliferative activity against human cell lines typical for breast cancer (MCF-7), ovarian cancer (A-2780), prostate cancer (DU145 and PC-3), and colon cancer (HT-29 and SW620) cells. It strongly inhibits the activation of the following carcinogens: 2-amino-3-methylimidazol-[4,5-f]quinoline and aflatoxin B1 (AFB1) via human cytochrome P450 (CYP1A2). It also inhibits the production of prostate specific antigen (PSA). IXN significantly reduces the expression of transforming growth factor-β (TGF-β) in the case of invasive breast cancer MDA-MB-231. It interferes with JAK/STAT signaling pathway and inhibits the expression of pro1inflammatory genes in the monoblastic leukemia cell line (MonoMac6). It activates apoptosis in human umbilical vein endothelial cells (HUVEC) and human aortic smooth muscle cells (HASMCs). In addition, IXN shows an antiviral activity towards herpes viruses (HSV1 and HSV2) and bovine viral diarrhea virus (BVDV).

Lactones 1. Hydroxylation of dihydro-β-campholenolactone by Fusarium culmorum

Abstract The stereospecific hydroxylation of racemic dihydro-β-campholenolactone ( 1 ) by several fungal strains has been evaluated. The 6-hydroxy derivative as a major product and 5-hydroxy as a minor one were isolated from transformation of 1 with Fusarium culmorum .

Loliolide – the most ubiquitous lactone

Abstract The searching for biologically active compounds produced by living organisms led to the discovery of a number of compounds with more or less complicated structure. One of the simplest molecules are monoterpenoid lactones and loliolide is the most common among them. Loliolide was found in animals (insects) and plants (flowers, shrubs, trees) both terrestrial and marine, such as algae and corals. Many years of research on plants used in traditional folk medicine of different countries have led to the conclusion that this compound has a variety of biological properties such as anti-cancer, antibacterial, antifungal and antioxidant ones. Moreover, plants containing loliolide are used in alternative medicine in treatment of diabetes and depression. It is extremely interesting that this lactone also affects the behavior of ants as well as the development of certain plants (allelopathic activity). However, sometimes there are side effects as in the case of structural analogues of loliolide contributing to extinction of tropical coral. Streszczenie Poszukiwania związków biologicznie aktywnych wytwarzanych przez organizmy żywe doprowadziły do odkrycia wielu związków o mniej lub bardziej skomplikowanej strukturze. Jednymi z najprostszych cząsteczek są laktony monoterpenoidowe, zaś najczęściej spotykanym spośród nich jest loliolid. Loliolid spotykany jest w organizmach zwierzęcych (owady) i roślinnych (rośliny kwiatowe, krzewy, drzewa) zarówno lądowych jak i morskich takich jak glony lub koralowce. Wieloletnie badania prowadzone nad roślinami używanymi w tradycyjnej medycynie ludowej różnych krajów doprowadziły do stwierdzenia, że związek ten ma różnorodne właściwości biologiczne np. antynowotworowe, antybakteryjne, antygrzybiczne, antyoksydacyjne. Ponadto rośliny zawierające lioliolid są stosowane w medycynie alternatywnej przy leczeniu cukrzycy oraz depresji. Niezmiernie interesujący jest fakt, że lakton ten wywiera również wpływ na zachowanie mrówek jak i na rozwój niektórych roślin (aktywność alleplopatyczna). Czasami jednak można zaobserwować również działania niepożądane jak w przypadku analogów strukturalnych loliolidu mających swój udział w wymieraniu raf tropikalnych.

Antioxidant activity and spectroscopic data of isoxanthohomol oxime and related compounds

Oximes of isoxanthohumol (IXN), naringenin (N) and flavanone (FL) were synthesized with yields of 88-95% and their antioxidant activity was evaluated using the 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) method. Although naringenin oxime (NOX) and flavanone oxime (FLOX) did not have any significant antioxidant effect (EC50=2.21 mM and 78.7 mM, respectively), isoxanthohumol oxime (IXNOX) showed a strong antioxidant activity (EC50=0.0411 mM), comparable to the activity of ascorbic acid (EC50=0.0181 mM). The structure of new compound IXNOX was established using (1)H NMR, (13)C NMR, IR and UV-VIS spectroscopy, by comparison to IXN, NOX and FLOX.

Biotransformation of 6,7-epoxygeraniol by fungi

The biotransformation of 6,7-epoxygeraniol by resting cells of selected fungi was investigated. The main product obtained from the transformation in Rhodotorula glutinis and R. marina cultures was 6,7-epoxynerol (5–48% of chloroform extracts), whereas Saccharomyces cerevisiae, Candida parapsilosis and C. kefyr reduced this substrate to 6,7-epoxycitronellol (30–33% of chloroform extracts). Cultures of Yarrowia lipolytica, Botrytis cinerea and S. cerevisiae promoted the cyclisation of 6,7-epoxygeraniol to 2-methyl-2-(2-hydroxyethyl)-5-(2-hydroxyprop-2-yl)tetrahydrofuran (11–99% of chloroform extracts). The biotransformation of 6,7-epoxynerol was also investigated. However, none of the tested micro-organisms converted this compound.

Modulation of the growth and metabolic response of cyanobacteria by the multifaceted activity of naringenin

The interactions between the plant-derived bioflavonoid, naringenin, and prokaryotic microalgae representatives (cyanobacteria), were investigated with respect to its influence on the growth and metabolic response of these microorganisms. To achieve reliable results, the growth of cyanobacteria was determined based on measurements of chlorophyll content, morphological changes were assessed through microscopic observations, and the chemical response of cells was determined using liquid and gas chromatography (HPLC; GC-FID). The results show that micromolar levels of naringenin stimulated the growth of cyanobacteria. Increased growth was observed for halophilic strains at naringenin concentrations below 40 mg L-1, and in freshwater strains at concentrations below 20 mg L-1. The most remarkable stimulation was observed for the freshwater species Nostoc muscorum, which had a growth rate that was up to 60% higher than in the control. When naringenin was examined at concentrations above 40 mg L-1, the growth of the tested microorganisms was inhibited. Simultaneously, an intensive excretion of exopolysaccharides was observed. Microscopic observations strongly suggest that these effects resulted from a structural disturbance of cyanobacterial cell walls that was exerted by naringenin. This phenomenon, in combination with the absorption of naringenin into cell wall structures, influenced cell permeability and thus the growth of bacteria. Fortunately, almost all the naringenin added to the culture was incorporated into to cell substructures and could be recovered through extraction, raising the possibility that this modulator could be recycled.

Synthesis and Biological Activity of Novel O-Alkyl Derivatives of Naringenin and Their Oximes

O-Alkyl derivatives of naringenin (1a–10a) were prepared from naringenin using the corresponding alkyl iodides and anhydrous potassium carbonate. The resulting products were used to obtain oximes (1b–10b). All compounds were tested for antimicrobial activity against Escherichia coli ATCC10536, Staphylococcus aureus DSM799, Candida albicans DSM1386, Alternaria alternata CBS1526, Fusarium linii KB-F1, and Aspergillus niger DSM1957. The resulting biological activity was expressed as the increase in optical density (ΔOD). The highest inhibitory effect against E. coli ATCC10536 was observed for 7,4′-di-O-pentylnaringenin (8a), 7-O-dodecylnaringenin (9a), naringenin oxime (NG-OX), 7,4′-di-O-pentylnaringenin oxime (8b), and 7-O-dodecylnaringenin oxime (9b) (ΔOD = 0). 7-O-dodecylnaringenin oxime (9b) also inhibited the growth of S. aureus DSM799 (ΔOD = 0.35) and C. albicans DSM1386 (ΔOD = 0.22). The growth of A. alternata CBS1526 was inhibited as a result of the action of 7,4′-di-O-methylnaringenin (2a), 7-O-ethylnaringenin (4a), 7,4′-di-O-ethylnaringenin (5a), 5,7,4′-tri-O-ethylnaringenin (6a), 7,4′-di-O-pentylnaringenin (8a), and 7-O-dodecylnaringenin (9a) (ΔOD in the range of 0.49–0.42) in comparison to that of the control culture (ΔOD = 1.87). In the case of F. linii KB-F1, naringenin (NG), 7,4′-di-O-dodecylnaringenin (10a), 7-O-dodecylnaringenin oxime (9b), and 7,4′-di-O-dodecylnaringenin oxime (10b) showed the strongest effect (ΔOD = 0). 7,4′-Di-O-pentylnaringenin (8a) and naringenin oxime (NG-OX) hindered the growth of A. niger DSM1957 (ΔOD = 0).

Influence of structure of lactones with the methylcyclohexene and dimethylcyclohexene ring on their biotransformation and antimicrobial activity

Abstract The aim of this article is influence of the structure of lactones with the methylcyclohexene and dimethylcyclohexene ring on their biotransformation and antimicrobial activity. This work was based on the general remark that even the smallest change in the structure of a compound can affect its biological properties. The results of the biotransformation of four bicyclic unsaturated lactones with one or two methyl groups in the cyclohexene ring was tested using fifteen fungal strains (Fusarium species, Penicillium species, Absidia species, Cunninghamella japonica, and Pleurotus ostreatus) and five yeast strains (Yarrowia lipolytica, Rhodorula marina, Rhodorula rubra, Candida viswanathii, and Saccharomyces cerevisiae). During these transformations, new epoxylactone and hydroxylactone were obtained. The relationship between the substrate structure and the ability of the microorganisms to transform them were analysed. Only compounds with C–O bond of lactone ring in the equatorial position were transformed by fungus. All presented here lactones were examined also for their antimicrobial activity. It turned out that these compounds exhibited growth inhibition of bacteria and fungi, mainly Bacillus subtilis, Candida albicans, Aspergillus niger, and Penicillium expansum.

Synthesis and Biotransformation of Bicyclic Unsaturated Lactones with Three or Four Methyl Groups

The aim of this study was to obtain new unsaturated lactones by chemical synthesis and their microbial transformations using fungal strains. Some of these strains were able to transform unsaturated lactones into different hydroxy or epoxy derivatives. Strains of Syncephalastrum racemosum and Absidia cylindrospora gave products with a hydroxy group introduced into a tertiary carbon, while the Penicillium vermiculatum strain hydroxylated primary carbons. The Syncephalastrum racemosum strain hydroxylated both substrates in an allylic position. Using the Absidia cylindrospora and Penicillium vermiculatum strains led to the obtained epoxylactones. The structures of all lactones were established on the basis of spectroscopic data.

Biotransformation of Bicyclic Halolactones with a Methyl Group in the Cyclohexane Ring into Hydroxylactones and Their Biological Activity

The aim of this study was the chemical synthesis of a series of halo- and unsaturated lactones, as well as their microbial transformation products. Finally some of their biological activities were assessed. Three bicyclic halolactones with a methyl group in the cyclohexane ring were obtained from the corresponding γ,δ-unsaturated ester during a two-step synthesis. These lactones were subjected to screening biotransformation using twenty two fungal strains. These strains were tested on their ability to transform halolactones into new hydroxylactones. Among the six strains able to catalyze hydrolytic dehalogenation, only two (Fusarium equiseti, AM22 and Yarrowia lipolytica, AM71) gave a product in a high yield. Moreover, one strain (Penicillium wermiculatum, AM30) introduced the hydroxy group on the cyclohexane ring without removing the halogen atom. The biological activity of five of the obtained lactones was tested. Some of these compounds exhibited growth inhibition against bacteria, yeasts and fungi and deterrent activity against peach-potato aphid.