Chalcone-Derived Lactones: Synthesis, Whole-Cell Biotransformation, and Evaluation of Their Antibacterial and Antifungal Activity.

Four compounds with lactone moiety were synthesized from chalcone 1 in three- or four-step synthesis. γ-Bromo-δ-lactone 5 was the only product of bromolactonization of acid 4 whereas bromolactonization of ester 3, apart from lactone 5 also afforded its isomer 6 and two diastereoisomeric δ-hydroxy-γ-lactones 7 and 8. Lactone 8 was also obtained in 88% yield as a product of simultaneous dehalogenation and translactonization of γ-bromo-δ-lactone 5 by Penicillum frequentans AM 359. Chalcone-derived lactones 5-8 were subjected to the tests on antimicrobial activity and the results compared with activity of starting chalcone 1. Obtained lactones 5-8 in most cases limited the growth of tested bacterial and fungal strains. The highest activity was found for δ-hydroxy-γ-lactone 8 which completely inhibited the growth of Staphylococcus aureus, Fusarium graminearum, Aspergillus niger, and Alternaria sp. The introduction of lactone moiety into chalcone scaffold significantly improved antimicrobial activity of the compound: γ-bromo-δ-lactone 6 and δ-hydroxy-γ-lactone 8 were significantly stronger growth inhibitors of S. aureus and F. graminearum. In the case of the latter, a clear positive effect of the lactone function on the antifungal activity was also observed for γ-bromo-δ-lactone 5.

Acylglycerols of Myristic Acid as New Candidates for Effective Stigmasterol Delivery-Design, Synthesis, and the Influence on Physicochemical Properties of Liposomes.

New carriers of phytosterols; acylglycerols containing natural myristic acid at sn-1 and sn-3 positions and stigmasterol residue linked to sn-2 position by carbonate and succinate linker have been designed and synthesized in three-step synthesis from dihydroxyacetone (DHA). The synthetic pathway involved Steglich esterification of DHA with myristic acid; reduction of carbonyl group of 1,3-dimyristoylpropanone and esterification of 1,3-dimyristoylglicerol with stigmasterol chloroformate or stigmasterol hemisuccinate. The structure of the obtained hybrids was established by the spectroscopic methods (NMR; IR; HRMS). Obtained hybrid molecules were used to form new liposomes in the mixture with model phospholipid and their effect on their physicochemical properties was determined, including the polarity, fluidity, and main phase transition of liposomes using differential scanning calorimetry and fluorimetric methods. The results confirm the significant effect of both stigmasterol-containing acylglycerols on the hydrophilic and hydrophobic region of liposome membranes. They significantly increase the order in the polar heads of the lipid bilayer and increase the rigidity in the hydrophobic region. Moreover, the presence of both acylglycerols in the membranes shifts the temperature of the main phase transition towards higher temperatures. Our results indicate stabilization of the bilayer over a wide temperature range (above and below the phase transition temperature), which in addition to the beneficial effects of phytosterols on human health makes them more attractive components of novel lipid nanocarriers compared to cholesterol.

Distigmasterol-Modified Acylglycerols as New Structured Lipids-Synthesis, Identification and Cytotoxicity.

Plant sterols, also referred as phytosterols, have been known as bioactive compounds which have cholesterol-lowering properties in human blood. It has been established that a diet rich in plant sterols or their esters alleviates cardiovascular diseases (CVD), and also may inhibit breast, colon and lung carcinogenesis. Phytosterols, in their free and esterified forms, are prone to thermo-oxidative degradation, where time and temperature affect the level of degradation. Looking for new derivatives of phytosterols with high thermo-oxidative stability for application in foods, our idea was to obtain novel structured acylglycerols in which two fatty acid parts are replaced by stigmasterol residues. In this work, asymmetric (1,2- and 2,3-) distigmasterol-modified acylglycerols (dStigMAs) were synthesized by the covalent attachment of stigmasterol residues to sn-1 and sn-2 or sn-2 and sn-3 positions of 3-palmitoyl-sn-glycerol or 1-oleoyl-sn-glycerol, respectively, using a succinate or carbonate linker. The chemical structures of the synthesized compounds were identified by NMR, HR-MS, and IR data. Moreover, the cytotoxicity of the obtained compounds was determined. The dStigMAs possessing a carbonate linker showed potent cytotoxicity to cells isolated from the small intestine and colon epithelium and liver, whereas the opposite results were obtained for compounds containing a succinate linker.

Methoxy-Substituted γ-Oxa-ε-Lactones Derived from Flavanones-Comparison of Their Anti-Tumor Activity In Vitro.

BACKGROUND: The study investigated four flavanone-derived γ-oxa-ε-lactones: a parent unsubstituted compound and its three derivatives with the methoxy group in positions 2', 4' and 8. Our objective was to find out if the introduction of the methoxy group into the aromatic ring affects in vitro anti-tumor potency of the investigated lactones. METHODS: Cytotoxic and pro-apoptotic effects were assessed with cytometric tests with propidium iodide, annexin V, and Western blot techniques. We also investigated potential synergistic potency of the tested lactones and glucocorticoids in canine lymphoma/leukemia cell lines. RESULTS: The tested flavanone-derived lactones showed anti-cancer activity in vitro. Depending on its location, the methoxy group either increased or decreased cytotoxicity of the derivatives as compared with the parent compound. The most potent lactone was the one with the methoxy group at position 4' of the B ring (compound 3), and the weakest activity was observed when the group was located at C-8 in the A ring. A combination of the lactones with glucocorticoids confirmed their synergy in anti-tumor activity in vitro. CONCLUSIONS: Methoxy-substituted flavanone-derived lactones effectively kill canine lymphoma/leukemia cells in vitro and, thanks to their synergistic action with glucocorticoids, may potentially be applied in the treatment of hematopoietic cancers.

Free and Immobilized Lecitase™ Ultra as the Biocatalyst in the Kinetic Resolution of (E)-4-Arylbut-3-en-2-yl Esters.

The influence of buffer type, co-solvent type, and acyl chain length was investigated for the enantioselective hydrolysis of racemic 4-arylbut-3-en-2-yl esters using Lecitase™ Ultra (LU). Immobilized preparations of the Lecitase™ Ultra enzyme had significantly higher activity and enantioselectivity than the free enzyme, particularly for 4-phenylbut-3-en-2-yl butyrate as the substrate. Moreover, the kinetic resolution with the immobilized enzyme was achieved in a much shorter time (24-48 h). Lecitase™ Ultra, immobilized on cyanogen bromide-activated agarose, was particularly effective, producing, after 24 h of reaction time in phosphate buffer (pH 7.2) with acetone as co-solvent, both (R)-alcohols and unreacted (S)-esters with good to excellent enantiomeric excesses (ee 90-99%). These conditions and enzyme were also suitable for the kinetic separation of racemic (E)-4-phenylbut-3-en-2-yl butyrate analogs containing methyl substituents on the benzene ring (4b,4c), but they did not show any enantioselectivity toward (E)-4-(4'-methoxyphenyl)but-3-en-2-yl butyrate (4d).

Microbial Asymmetric Functionalization of ß-Cyclocitral-Derived Tetramethyl-Substituted γ-Lactone.

Searching for the new anticancer compounds we prepared three new ß-cyclocitral-derived hydroxyl-γ-lactones by microbial hydroxylation of tetramethyl-substituted bicyclic γ-lactone. The substrate was transformed by the enzymatic system of filamentous fungi. Three out of fifteen strains were selected as effective biocatalysts (Fusarium culmorum AM10, Armillaria mellea AM296, Trametes versicolor AM536). The hydroxylation processes were not only regioselective but also stereoselective. The hydroxylation products of each secondary carbon atom in the cyclohexane ring were obtained by the application of the selected fungal strains. The Fusarium culmorum AM10 introduced the hydroxy function at C-3 and C-4, Armillaria mellea AM296 incorporated the hydroxy function at C-3 and C-5 and Trametes versicolor AM536 transformed the substrate to the mixture of C-3, C-4 and C-5 hydroxylactones. The hydroxylactones obtained were enantiomericaly enriched (ee values in the range 17⁻99%). The in vitro antiproliferative activities of the functionalization products were also evaluated. Regardless of the hydroxy substituent location all tested lactones exhibited similar, significant activity towards selected cancer cell lines (IC50 in the range 22.8⁻33.9 µg/mL).

Synthesis and Antimicrobial Activity of Methoxy- Substituted γ-Oxa-ε-lactones Derived from Flavanones.

Six γ-oxa-ε-lactones, 4-phenyl-3,4-dihydro-2H-1,5-benzodioxepin-2-one (5a) and its five derivatives with methoxy groups in different positions of A and B rings (5b-f), were synthesized from corresponding flavanones. Three of the obtained lactones (5b,c,f) have not been previously described in the literature. Structures of all synthesized compounds were confirmed by complete spectroscopic analysis with the assignments of signals on 1H and 13C-NMR spectra to the corresponding atoms. In most cases, lactones 5a-f exerted an inhibitory effect on the growth of selected pathogenic bacteria (Escherichia coli, Bacillus subtilis, and Staphylococcus aureus), filamentous fungi (Fusarium graminearum, Aspergillus niger, and Alternaria sp.), and yeast (Candida albicans). The broadest spectrum of activity was observed for unsubstituted lactone 5a, which was particularly active against filamentous fungi and yeast. Lactones with methoxy groups in the 3' (5c) and 4' (5d) position of B ring were more active towards bacteria whereas lactone substituted in the 7 position of the A ring (5e) exhibited higher antifungal activity. In most cases, the introduction of lactone function increased the activity of the compound compared to its flavonoid precursors, chalcones 3a-e, and flavanones 4a-f.

Enantiomeric trans ß-aryl-δ-iodo-γ-lactones derived from 2,5-dimethylbenzaldehyde induce apoptosis in canine lymphoma cell lines by downregulation of anti-apoptotic Bcl-2 family members Bcl-xL and Bcl-2.

For many years, studies focused on developing new natural or synthetic compounds with antineoplastic activity have attracted the attention of researchers. An interesting group of such compounds seem to be those with both lactone moiety and an aromatic ring which, in addition to antimicrobial or antiviral activity, also exhibit antitumor properties. The study shows antitumor activity of two enantiomeric trans isomers of 5-(1-iodoethyl)-4-(2',5'-dimethylphenyl)dihydrofuran-2-one. Our aim was to determine their antitumor activity manifested as an ability to induce apoptosis in selected canine cancer cell lines as well as to evaluate differences in their strength depending on the configuration of their stereogenic centers. The enantiomers (+)-(4R,5S,6R)-1 and (-)-(4S,5R,6S)-2 were found to induce classical caspase-dependent apoptosis through downregulation of the expression of anti-apoptotic proteins Bcl-xL and Bcl-2. Although the mechanism of apoptosis induction was the same for both enantiomers, they differed in their strength, as stronger antineoplastic activity in vitro was exhibited by isomer (+)-(4R,5S,6R)-1.

Microbial Hydrolysis of Racemic ß-Aryl-γ-ethylidene-γ-lactones and Antifeedant Activity of the Products against Alphitobius diaperinus Panzer.

Hydrolysis of (±)-ß-aryl-γ-ethylidene-γ-lactones by fungal strain Aspergillus ochraceus AM370 afforded (−)-(S)-γ-ethylidene-γ-lactones 2a⁻d and (+)-(R)-γ-ketoacids 3a⁻d. Enantiomeric purity of the unreacted lactones was strictly related to a size of an aryl substituent at C-4 of γ-lactone ring, with the highest ee (77%) obtained for the (−)-(S)-γ-ethylidene-γ-lactone possessing unsubstituted benzene ring (2a) and the lowest one (15%) determined for the (−)-(S)-γ-ethylidene-γ-lactone with bulky 1,3-benzodioxole system (2d). Lactones 2a⁻d, both racemic and enantiomerically enriched, as well as products of their hydrolysis showed varying degrees of feeding deterrent activity against lesser mealworm, Alphitobius diaperinus Panzer, which depended on the structure of the compound and the developmental stage of the lesser mealworm. In the case of adults, more active were γ-lactones 2a⁻d, compared with ketoacids 3a⁻d. Only in the case of lactone 2a was the effect of configuration of stereogenic center on the activity found. Particularly strong deterrents against this stage (T > 180) were racemic and (−)-(S)-γ-ethylidene-γ-lactone with p-methoxysubstituted phenyl ring (2c).

Preparation of Enantiomeric ß-(2',5'-Dimethylphenyl)Bromolactones, Their Antiproliferative Activity and Effect on Biological Membranes.

Three novel enantiomeric pairs of bromolactones possesing a 2,5-dimethylphenyl substituent at the ß-position of the lactone ring have been synthesized from corresponding enantiomeric (E)-3-(2',5'-dimethylphenyl)hex-4-enoic acids (4) by kinetically controlled bromolactonization with N-bromosuccinimide (NBS). γ-Bromo-δ-lactones (5) were isolated as the major products. Absolute configurations of stereogenic centers of γ-bromo-δ-lactones (5) were assigned based on X-ray analysis; configurations of cis δ-bromo-γ-lactones (6) and trans δ-bromo-γ-lactones (7) were determined based on mechanism of bromolactonization. Synthesized compounds exhibited significant antiproliferative activity towards the four canine cancer cell lines (D17, CLBL-1, CLB70, and GL-1) and one human cancer line (Jurkat). Classifying the compounds in terms of activity, the most active were enantiomers of trans δ-bromo-γ-lactones (7) followed by enantiomers of cis isomer (6) and enantiomeric γ-bromo-δ-lactones (5). Higher activity was observed for all stereoisomers with S configuration at C-4 in comparison with their enantiomers with 4R configuration. Synthesized compounds did not induce hemolysis of erythrocytes. The results of the interaction of bromolactones with red blood cell membranes suggest that these compounds incorporate into biological membranes, concentrating mainly in the hydrophilic part of the bilayer but have practically no influence on fluidity in the hydrophobic region. The differences in interactions with the membrane between particular enantiomers were observed only for γ-lactones: stronger interactions were found for enantiomer 4R,5R,6S of cis γ-lactone (6) and for enantiomer 4S,5R,6S of trans γ-lactone (7).

Lipase-Catalyzed Transesterification of Egg-Yolk Phophatidylcholine with Concentrate of n-3 Polyunsaturated Fatty Acids from Cod Liver Oil.

Phospholipids containing PUFAs are important vehicles for their delivering to the targeted tissues. In our research project we established enzymatic methods for the enrichment of natural egg-yolk PC with n-3 PUFAs. Instead of synthetic PUFA ethyl esters, the new strategy was developed using polyunsaturated fatty acids enriched fraction (PUFA-EF) from cod liver oil as the natural acyl donors. PUFA-EF was produced by urea-complexation and contained 86.9% PUFA including 8.5% stearidonic acid (SDA; 18:4(n-3)), 26.7% EPA, and 45.2% DHA. The transesterification of PC with PUFA was catalyzed by lipases. After screening of enzymes the effect of reaction medium; molar ratio of substrates and etc. was investigated. The highest incorporation of PUFA was 45.6%; including 36.8% DHA and 5.8% EPA at the following reaction conditions: hexane; 55 °C; PUFA-EF/PC acyl ratio of 10; 48 h of reaction time and lipase B from Candida antarctica as a biocatalyst (20% of enzyme load).

Stereoselective yeast-mediated reduction of trans-5-(1'-oxo-3'-methylbutyl)-3-methyldihydrofuran-2-one: production of chiral intermediates for the synthesis of ß-secretase inhibitors.

OBJECTIVE: To investigate the usefulness of yeast strains to the production of chiral hydroxylactones, important synthons in the synthesis of ß-secretase inhibitors. RESULTS: Strains Rhodotorula glutinis KCh 242, Rhodotorula rubra KCh 82, Rhodotorula marina KCh 77 and Saccharomyces cerevisiae KCh 464 reduced racemic trans-5-(1'-oxo-3'-methylbutyl)-3-methyldihydrofuran-2-one (4) according to the Prelog's rule to afford preferentially the stereoisomers with S configurations at C-1'. R. marina KCh 77 and R. glutinis KCh 242 exhibited selectivity towards 3S, 5R enantiomer of the substrate, whereas R. rubra KCh 82 and S. cerevisiae KCh 464 preferred the reduction of its antipode. The highest yield of 3R,5S,1'S-hydroxylactone 3c (78 %) was obtained with R. rubra KCh 82. CONCLUSIONS: Different stereoisomers of trans-5-(1'-hydroxy-3'-methylbutyl)-3-methyldihydrofuran-2-one and its 5-substituted analogues are produced as important intermediates in the synthesis of drugs for the therapy of Alzheimer's disease.

Dehalogenation Activity of Selected Fungi Toward δ-Iodo-γ-Lactone Derived from trans,trans-Farnesol.

Time-course of biotransformation of racemic trans-4-((E)-4',8'-dimethylnona-3',7'-dien-1-yl)-5-iodomethyl-4-methyldihydrofuran-2-one (1) in fungal and yeast cultures was investigated. In these conditions, the substrate 1 was enantioselectively dehalogenated yielding 4-((E)-4',8'-dimethylnona-3',7'-dien-1-yl)-4-methyl-5-methylenedihydrofuran-2-one (2) and its structure was established based on the spectroscopic data. The most effective biocatalyst used was Didymosphaeria igniaria, which catalyzed the process with highest rate and enantioselectivity (ee of product = 76%). The antiproliferative activity of δ-iodo-γ-lactone 1, product of its biotransformation 2, and starting substrate (farnesol) were evaluated toward two cancer cell lines: A549 (human lung adenocarcinoma) and HL-60 (human promyelocytic leukemia).

Chemoenzymatic Synthesis of trans-ß-Aryl-δ-hydroxy-γ-lactones and Enzymatic Kinetic Resolution of Their Racemic Mixtures.

Two novel and convenient routes to obtain enantiomerically enriched trans-ß-aryl-δ-hydroxy-γ-lactones 5a-d with potential antifeedant and anticancer activity were developed. In the first method starting from corresponding enantiomers of γ,δ-unsaturated esters 4a-d derived from enzymatically resolved allyl alcohols 1a-d, both enantiomers of hydroxylactones 5a-d were synthesized with high enantiomeric excesses (73%-97%). Configurations of the stereogenic centers of the synthesized compounds were assigned based on the mechanism of acidic lactonization of esters 4a-d in the presence of m-chloroperbenzoic acid (m-CPBA). An alternative method for the production of optically active trans-ß-aryl-δ-hydroxy-γ-lactones 5a-d was lipase-catalyzed kinetic resolution of their racemic mixtures by transesterification with vinyl propionate as the acyl donor. The most efficient enzyme in the screening procedure was lipase B from Candida antarctica. Its application on a preparative scale after 6 h afforded unreacted (+)-(4S,5R,6S)-hydroxylactones 5a-d and (+)-(4R,5S,6R)-propionates 6a-d, most of them with high enantiomeric excesses (92%-98%). Resolution of lactone 5d with bulky 1,3-benzodioxol ring provided products with significantly lower optical purity (ee = 89% and 84% for hydroxylactone 5d and propionate 6d, respectively). The elaborated methods give access to both enantiomers of trans-ß-aryl-δ-hydroxy-γ-lactones 5a-d with the defined absolute configurations of stereogenic centers, which is crucial requirement for the investigations of relationship: spatial structure-biological activity.

Enantioselective Microbial Hydroxylation as a Useful Tool in the Production of Jasmonate Derivatives with Aphid Deterrent Activity.

Microbial transformations of two natural compounds dihydrojasmone (1) and cis-jasmone (3) in the growing cultures of selected twenty strains have been investigated. The studies have demonstrated a biocatalytic potential of tested microorganisms for the enantioselective hydroxylation of jasmonates. The substrates underwent an effective regio- and stero-selective hydroxylation at the allylic position in the cyclopentenone ring, and the corresponding optically pure keto-alcohols (2, 4) were obtained. The process of biohydroxylation depended on the composition of reaction medium. In the studied cultures, (+)-(R)-4-hydroxydihydrojasmone (2) and (+) and (-)-4-hydroxyjasmone (4a, 4b) were produced in good yields and high enantiomeric excesses. Moreover, the introduction of the hydroxy group into the molecule of jasmonate ketones 1 and 3 leads to biologically active derivatives 2 and 4 that regulate the behaviour of aphids Myzus persicae by termination of their feeding.

Conjugates of 1,3- and 1,2-Acylglycerols with Stigmasterol: Synthesis, NMR Characterization, and Impact on Lipid Bilayers.

The main aim of research was synthesis and spectroscopic characterization of new conjugates in which stigmasterol was linked via carbonate or succinyl linker with 1,3- and 1,2-acylglycerols of palmitic and oleic acid. Acylglycerols containing stigmasterol residue at internal position have been synthesized from 2-benzyloxypropane-1,3-diol or dihydroxyacetone. Their asymmetric counterparts containing stigmasterol residue attached to sn-3 position have been obtained from (S)-solketal. Eight synthesized conjugates were used to create the liposomes as nanocarriers of phytosterols to increase their stability and protect them from degradation during thermal-oxidative treatments. Fluorimetric and ATR-FTIR methods were used to determine the impact of synthesized conjugates on the physicochemical properties of the lipid bilayer. The results indicate that conjugates with palmitic acid are better candidates for use as the potential stigmasterol nanocarriers compared to those with oleic acid because they increase the stiffness of the lipid bilayer and temperature of the main phase transition. The obtained results are the first step in designing of stigmasterol-enriched liposomal carriers with higher thermo-oxidative stability for their potential use in the food industry.

Production of erythritol and mannitol by Yarrowia lipolytica yeast in media containing glycerol.

Glycerol is a by-product generated in large amounts during the production of biofuels. This study presents an alternative means of crude glycerol valorization through the production of erythritol and mannitol. In a shake-flasks experiment in a buffered medium, nine Yarrowia lipolytica strains were examined for polyols production. Three strains (A UV'1, A-15 and Wratislavia K1) were selected as promising producers of erythritol or/and mannitol and used in bioreactor batch cultures and fed-batch mode. Pure and biodiesel-derived crude glycerol media both supplemented (to 2.5 and 3.25 %) and not-supplemented with NaCl were applied. The best results for erythritol biosynthesis were achieved in medium with crude glycerol supplemented with 2.5 % NaCl. Wratislavia K1 strain produced up to 80.0 g l⁻¹ erythritol with 0.49 g g⁻¹ yield and productivity of 1.0 g l⁻¹ h⁻¹. Erythritol biosynthesis by A UV'1 and A-15 strains was accompanied by the simultaneous production of mannitol (up to 27.6 g l⁻¹). Extracellular as well as intracellular erythritol and mannitol ratios depended on the glycerol used and the presence of NaCl in the medium. The results from this study indicate that NaCl addition to the medium improves erythritol biosynthesis, and simultaneously inhibits mannitol formation.

Lipase-mediated Baeyer-Villiger oxidation of benzylcyclopentanones in ester solvents and deep eutectic solvents.

This work presents the chemo-enzymatic Baeyer-Villiger oxidation of α-benzylcyclopentanones in ester solvents as well as deep eutectic solvents (DES). In the first part of the work the effect of selected reaction conditions on the reaction rate was determined. The oxidation process was most effective in ethyl acetate at 55 °C, with the use of lipase B from Candida antarctica immobilized on acrylic resin and UHP as oxidant. Ultimately, these preliminary studies prompted the development of an effective method for the implementation of lipase-mediated Baeyer-Villiger oxidation of benzylcyclopentanones in DES. The highest conversion was indicated when the oxidizing agent was a component of DESs (minimal DESs). The fastest conversion of ketones to lactones was observed in a mixture of choline chloride with urea hydrogen peroxide. In this case, after 3 days, the conversion of the ketones to lactones products exceeded 92% for all substrates. As a result, two new lactones were obtained and fully characterized by spectroscopic data.

Effect of Distigmasterol-Modified Acylglycerols on the Fluidity and Phase Transition of Lipid Model Membranes.

Plant sterols are known for their health-promoting effects, lowering blood cholesterol levels and alleviating cardiovascular disease. In this work, we continue our research on the asymmetric acylglycerols in which fatty acid residues are replaced by two stigmasterol residues in sn-1 and sn-2 or sn-2 and sn-3 positions as new thermostable carriers of phytosterols for their potential application in foods or as components of new liposomes in the pharmaceutical industry. The aim of this manuscript was to compare and analyze the effects of four distigmasterol-modified acylglycerols (dStigMAs) on the fluidity and the main phase transition temperature of the model phospholipid membrane. Their properties were determined using differential scanning calorimetry (DSC), steady-state fluorimetry and attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR). The determination of the effect of the tested compounds on the mentioned physicochemical parameters of the model membranes will allow for the determination of their properties and stability, which is essential for their practical application. The results indicated that all compounds effect on the physicochemical properties of the model membrane. The degree of these changes depends on the structure of the compound, especially the type of linker by which stigmasterol is attached to the glycerol backbone, as well as on the type of hydrocarbon chain.

Antiproliferative, Antimicrobial and Antiviral Activity of ß-Aryl-δ-iodo-γ-lactones, Their Effect on Cellular Oxidative Stress Markers and Biological Membranes.

The aim of this work was the examination of biological activity of three selected racemic cis-ß-aryl-δ-iodo-γ-lactones. Tested iodolactones differed in the structure of the aromatic fragment of molecule, bearing isopropyl (1), methyl (2), or no substituent (3) on the para position of the benzene ring. A broad spectrum of biological activity as antimicrobial, antiviral, antitumor, cytotoxic, antioxidant, and hemolytic activity was examined. All iodolactones showed bactericidal activity against Proteus mirabilis, and lactones 1,2 were active against Bacillus cereus. The highest cytotoxic activity towards HeLa and MCF7 cancer cell lines and NHDF normal cell line was found for lactone 1. All assessed lactones significantly disrupted antioxidative/oxidative balance of the NHDF, and the most harmful effect was determined by lactone 1. Contrary to lactone 1, lactones 2 and 3 did not induce the hemolysis of erythrocytes after 48 h of incubation. The differences in activity of iodolactones 1-3 in biological tests may be explained by their different impact on physicochemical properties of membrane as the packing order in the hydrophilic area and fluidity of hydrocarbon chains. This was dependent on the presence and type of alkyl substituent. The highest effect on the membrane organization was observed for lactone 1 due to the presence of bulky isopropyl group on the benzene ring.