Research

12 pages, 963 KiB

Open AccessArticle

Microbial Transformation of Galangin Derivatives and Cytotoxicity Evaluation of Their Metabolites

by Fubo Han, Yina Xiao and Ik-Soo Lee

Catalysts 2021, 11(9), 1020; https://doi.org/10.3390/catal11091020 - 24 Aug 2021

Cited by 3 | Viewed by 2051

Galangin (1), 3-O-methylgalangin (2), and galangin flavanone (3), the major bioactive flavonoids isolated from Alpinia officinarum, were biotransformed into one novel and four known metabolites (4–8) by application of the fungal [...] Read more.

Galangin (1), 3-O-methylgalangin (2), and galangin flavanone (3), the major bioactive flavonoids isolated from Alpinia officinarum, were biotransformed into one novel and four known metabolites (4–8) by application of the fungal strains Mucor hiemalis and Absidia coerulea as biocatalysts. Their structures were characterized by extensive spectroscopic analyses including one- and two-dimensional nuclear magnetic resonance spectroscopy and mass spectrometry. Compounds 1–7 were evaluated for their cytotoxic activities against cancer cell lines using the MTT assay. The new compound 3-O-methylgalangin-7-O-β-D-glucopyranoside (6) exhibited the most potent cytotoxic activity against MCF-7, A375P, B16F10, B16F1, and A549 cancer cell lines with the IC₅₀ values at 3.55–6.23 μM. Full article

(This article belongs to the Special Issue Catalysis in the Synthesis of Biologically Active Compounds)

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20 pages, 1244 KiB

Open AccessArticle

Bacterial Whole Cells Synthesis of Whisky Lactones in a Solid-State Fermentation Bioreactor Prototype

by Dawid Hernik, Jakub Pannek, Ewa Szczepańska, Teresa Olejniczak and Filip Boratyński

Catalysts 2021, 11(3), 320; https://doi.org/10.3390/catal11030320 - 01 Mar 2021

Cited by 2 | Viewed by 2042

Abstract

Agro-industrial side streams such as oilseed cakes were used as a medium in solid-state fermentation (SSF) for microbial oxidation of anti- and syn-3-methyl-octane-1,4-diols to obtain corresponding trans- and cis-whisky lactones. In preliminary screening transformations, a wide range of whole [...] Read more.

Agro-industrial side streams such as oilseed cakes were used as a medium in solid-state fermentation (SSF) for microbial oxidation of anti- and syn-3-methyl-octane-1,4-diols to obtain corresponding trans- and cis-whisky lactones. In preliminary screening transformations, a wide range of whole bacterial cells were tested on the basis of oxidation activity, which is rarely described in the literature, in contrast to the widely studied lipolytic activity on SSF. Among the different oil cakes tested, biotransformations carried out on linseed cake were characterized by the highest conversion and stereoselectivity. Several preparative-scale oxidations performed in a self-constructed SSF bioreactor catalyzed by Rhodococcus erythropolis DSM44534, Rhodococcus erythropolis PCM2150 and Gordonia rubripertincta PCM2144 afforded optically active trans-(+)-(4S,5R), cis-(+)-(4R,5R) and cis-(-)-(4S,5S) isomers of whisky lactones, respectively. Bacteria of the Rhodococcus, Gordonia, Dietzia and Streptomyces genera carried out transformations with complete conversion after three days. Various extraction methods were applied for the isolation of the products, and among them, the combination of steam distillation with simple extraction were the most efficient. Biotransformations were conducted under precise control of conditions in a bioreactor based on a Raspberry Pi Zero W. The proposed low-cost (ca. USD 100) bioreactor is a standalone system that is fully autoclavable and easy to use. Full article

(This article belongs to the Special Issue Catalysis in the Synthesis of Biologically Active Compounds)

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12 pages, 993 KiB

Open AccessFeature PaperArticle

New Bromo- and Iodo-Hydroxylactones with Two Methyl Groups Obtained by Biotransformation of Bicyclic Halolactones

by Małgorzata Grabarczyk, Wanda Mączka, Gabriela Maciejewska and Katarzyna Wińska

Catalysts 2021, 11(1), 73; https://doi.org/10.3390/catal11010073 - 07 Jan 2021

Viewed by 1587

Abstract

The subject of the research was to determine the ability of the filamentous fungi to biotransform bicyclic halolactones containing two methyl groups in their structure. By chemical synthesis three bicyclic halolactones with two methyl groups, one in the cyclohexane ring and one in [...] Read more.

The subject of the research was to determine the ability of the filamentous fungi to biotransform bicyclic halolactones containing two methyl groups in their structure. By chemical synthesis three bicyclic halolactones with two methyl groups, one in the cyclohexane ring and one in the lactone ring, were obtained: 2-chloro-4,7-dimethyl-9-oxabicyclo[4.3.0]nonan-8-one, 2-bromo-4,7-dimethyl-9-oxabicyclo[4.3.0]nonan-8-one, and 2-iodo-4,7-dimethyl-9-oxabicyclo[4.3.0]nonan-8-one. These compounds were formed as mixtures of two diastereoisomers. The obtained halolactones (as mixture of two diastereoisomers) were subjected to screening biotransformation with the use of eight strains of filamentous fungi: Fusarium culmorum AM10, F. avenaceum AM12, F. semitectum AM20, F. solani AM203, Absidia coerulea AM93, A. cylindrospora AM336, Penicillium chermesinum AM113, P. frequentans AM351. Two of the substrates, 2-bromo-4,7-dimethyl-9-oxabicyclo[4.3.0]nonan-8-one and 2-iodo-4,7-dimethyl-9-oxabicyclo[4.3.0]nonan-8-one, were hydroxylated without removing the halogen atom from the molecule, giving 2-bromo-7-hydroxy-4,7-dimethyl-9-oxabicyclo[4.3.0]nonan-8-one, 2-bromo-5-hydroxy-4,7-dimethyl-9-oxabicyclo[4.3.0]nonan-8-one, and 2-iodo-7-hydroxy-4,7-dimethyl-9-oxabicyclo[4.3.0]nonan-8-one as products. The hydroxylation capacity was demonstrated by strains of Absidia cylindrospora AM336, Fusarium avenaceum AM12, and F. solani AM203. The structures of all lactones were determined on the basis spectroscopic data. Full article

(This article belongs to the Special Issue Catalysis in the Synthesis of Biologically Active Compounds)

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14 pages, 3426 KiB

Open AccessArticle

Tel-Cu-NPs Catalyst: Synthesis of Naphtho[2,3-g]phthalazine Derivatives as Potential Inhibiters of Tyrosinase Enzymes and Their Investigation in Kinetic, Molecular Docking, and Cytotoxicity Studies

by Keerthana Selvaraj, Ali Daoud, Saud Alarifi and Akbar Idhayadhulla

Catalysts 2020, 10(12), 1442; https://doi.org/10.3390/catal10121442 - 09 Dec 2020

Cited by 10 | Viewed by 1734

Abstract

Novel one-pot synthesis naphtho[2,3-g]phthalazine (1a–1k) of Mannich base derivatives can be achieved via grindstone chemistry using a Tel-Cu-NPs (telmisartan-copper nanoparticles) catalyst. This method offers efficient mild reaction conditions and high yields. Tyrosinase inhibitory activity was evaluated for all synthesized [...] Read more.

Novel one-pot synthesis naphtho[2,3-g]phthalazine (1a–1k) of Mannich base derivatives can be achieved via grindstone chemistry using a Tel-Cu-NPs (telmisartan-copper nanoparticles) catalyst. This method offers efficient mild reaction conditions and high yields. Tyrosinase inhibitory activity was evaluated for all synthesized compounds, along with analysis of kinetic behavior and molecular docking studies. The synthesized compound, 1c was (IC₅₀ = 11.5 µM) more active than kojic acid (IC₅₀ = 78.0 µM). Lineweaver Burk plots were used to analyze the kinetic behavior of the most active compound 1c, it was reversible and competitive behavior. Compound 1c and kojic acid occurred in the presence of 2-hydroxyketone, which has the same inhibitory mechanism. The molecular docking of compound 1c and the control kojic acid were docked against 2Y9X protein via the Schrodinger Suite. The compound 1c showed a respectable dock score (−5.6 kcal/mol) compared to kojic acid with a dock score of (−5.2 kcal/mol) in the 2Y9X protein. Cytotoxicity activity was also evaluated by using HepG2 (liver), MCF-7 (breast), and HeLa (cervical) cancer cell lines, and high activity for 1c (GI₅₀ = 0.01, 0.03, and 0.04 µM, respectively) against all cell lines was found compared to standard and other compounds. Therefore, this study succeeded in testing a few promising molecules as potential antityrosinase agents. Full article

(This article belongs to the Special Issue Catalysis in the Synthesis of Biologically Active Compounds)

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10 pages, 1458 KiB

Open AccessArticle

Biotechnological Approach for the Production of Enantiomeric Hydroxylactones Derived from Benzaldehyde and Evaluation of Their Cytotoxic Activity

by Marcelina Mazur, Anna Kudrynska, Aleksandra Pawlak, Beatriz Hernandez-Suarez, Bożena Obmińska-Mrukowicz and Witold Gładkowski

Catalysts 2020, 10(11), 1313; https://doi.org/10.3390/catal10111313 - 13 Nov 2020

Cited by 3 | Viewed by 1490

Abstract

The β-aryl-δ-halo-γ-lactones are known for their antiproliferative activity towards numerous cancer cell lines. The aim of this study was to obtain in the biotransformation process new β-aryl-δ-hydroxy-γ-lactones and compare their activity with the antiproliferative activity of parent compounds. The racemic cis-5-(1-iodoethyl)-4-phenyldihydrofuran-2-one as [...] Read more.

The β-aryl-δ-halo-γ-lactones are known for their antiproliferative activity towards numerous cancer cell lines. The aim of this study was to obtain in the biotransformation process new β-aryl-δ-hydroxy-γ-lactones and compare their activity with the antiproliferative activity of parent compounds. The racemic cis-5-(1-iodoethyl)-4-phenyldihydrofuran-2-one as well as separate enantiomers were transformed in fungal cultures. Among ten tested biocatalysts, three (Absidia cylindrospora AM336, Absidia glauca AM254, and Fusarium culmorum AM10) were able to catalyze the hydrolytic dehalogenation process. The biotransformations processes were highly stereoselective and enantiomerically pure hydroxylactones were obtained (ee ≥ 99%). The iodo- and hydroxylactone enantiomers were subjected to cytotoxic activity evaluation on canine leukemia and lymphoma cell lines. The iodolactones exhibited higher biological potential towards tested cell lines than hydroxylactones. Higher cytotoxic potential was also characteristic for (+)-(4S,5S,6R)-enantiomer of iodolactone compared to its antipode. Full article

(This article belongs to the Special Issue Catalysis in the Synthesis of Biologically Active Compounds)

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11 pages, 1030 KiB

Open AccessArticle

Biotransformation of Hydroxychalcones as a Method of Obtaining Novel and Unpredictable Products Using Whole Cells of Bacteria

by Joanna Kozłowska, Bartłomiej Potaniec and Mirosław Anioł

Catalysts 2020, 10(10), 1167; https://doi.org/10.3390/catal10101167 - 12 Oct 2020

Cited by 6 | Viewed by 2225

Abstract

The aim of our study was the evaluation of the biotransformation capacity of hydroxychalcones—2-hydroxy-4′-methylchalcone (1) and 4-hydroxy-4′-methylchalcone (4) using two strains of aerobic bacteria. The microbial reduction of the α,β-unsaturated bond of 2-hydroxy-4′-methylchalcone (1) in Gordonia sp. [...] Read more.

The aim of our study was the evaluation of the biotransformation capacity of hydroxychalcones—2-hydroxy-4′-methylchalcone (1) and 4-hydroxy-4′-methylchalcone (4) using two strains of aerobic bacteria. The microbial reduction of the α,β-unsaturated bond of 2-hydroxy-4′-methylchalcone (1) in Gordonia sp. DSM 44456 and Rhodococcus sp. DSM 364 cultures resulted in isolation the 2-hydroxy-4′-methyldihydrochalcone (2) as a main product with yields of up to 35%. Additionally, both bacterial strains transformed compound 1 to the second, unexpected product of reduction and simultaneous hydroxylation at C-4 position—2,4-dihydroxy-4′-methyldihydrochalcone (3) (isolated yields 12.7–16.4%). During biotransformation of 4-hydroxy-4′-methylchalcone (4) we observed the formation of three products: reduction of C=C bond—4-hydroxy-4′-methyldihydrochalcone (5), reduction of C=C bond and carbonyl group—3-(4-hydroxyphenyl)-1-(4-methylphenyl)propan-1-ol (6) and also unpredictable 3-(4-hydroxyphenyl)-1,5-di-(4-methylphenyl)pentane-1,5-dione (7). As far as our knowledge is concerned, compounds 3, 6 and 7 have never been described in the scientific literature. Full article

(This article belongs to the Special Issue Catalysis in the Synthesis of Biologically Active Compounds)

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19 pages, 6448 KiB

Open AccessArticle

Entomopathogenic Filamentous Fungi as Biocatalysts in Glycosylation of Methylflavonoids

by Agnieszka Krawczyk-Łebek, Monika Dymarska, Tomasz Janeczko and Edyta Kostrzewa-Susłow

Catalysts 2020, 10(10), 1148; https://doi.org/10.3390/catal10101148 - 04 Oct 2020

Cited by 13 | Viewed by 1832

Abstract

Flavonoids are known for their numerous biological activities; however, their pharmacological application is limited by poor bioavailability. Glycosides are usually more stable and more soluble in water and in this form, flavonoids are present in nature. Likewise, the presence of the methyl group [...] Read more.

Flavonoids are known for their numerous biological activities; however, their pharmacological application is limited by poor bioavailability. Glycosides are usually more stable and more soluble in water and in this form, flavonoids are present in nature. Likewise, the presence of the methyl group in the flavonoid skeleton results in facilitated absorption and greater bioavailability. Entomopathogenic filamentous fungi are effective in the biotransformation of flavonoids; they are known especially for efficient glycosylation. In the current study we used strains of Beauveria bassiana KCH J1.5 and Isaria fumosorosea KCH J2 to biotransform flavonoids with a single methyl group. 2′-Hydroxy-5′-methylchalcone was biotransformed by both strains into 2′-hydroxy-5′-methylchalcone 3-O-β-D-(4″-O-methyl)-glucopyranoside. In the culture of B. bassiana KCH J1.5 four products were obtained from 6-methylflavanone: 4′-hydroxy-6-methylflavanone 3′-O-β-D-(4″-O-methyl)-glucopyranoside; 4′-hydroxyflavanone 6-methylene-O-β-D-(4″-O-methyl)-glucopyranoside; 6-hydroxymethylflavanone 3′-O-β-D-(4″-O-methyl)-glucopyranoside and 4′-hydroxy-6-hydroxymethylflavanone 3′-O-β-D-(4″-O-methyl)-glucopyranoside. Biotransformation with I. fumosorosea KCH J2 as a biocatalyst resulted in the formation of 6-methylflavanone 4′-O-β-D-(4″-O-methyl)-glucopyranoside and 2-phenyl-6-methylchromane 4-O-β-D-(4″-O-methyl)-glucopyranoside. All of these flavonoids can be used in biological activity tests and can be useful in studies concerning structure—bioactivity relationships. Full article

(This article belongs to the Special Issue Catalysis in the Synthesis of Biologically Active Compounds)

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13 pages, 1320 KiB

Open AccessArticle

Highly Effective, Regiospecific Hydrogenation of Methoxychalcone by Yarrowia lipolytica Enables Production of Food Sweeteners

by Mateusz Łużny, Ewa Kozłowska, Edyta Kostrzewa-Susłow and Tomasz Janeczko

Catalysts 2020, 10(10), 1135; https://doi.org/10.3390/catal10101135 - 01 Oct 2020

Cited by 7 | Viewed by 2120

Abstract

We describe the impact of the number and location of methoxy groups in the structure of chalcones on the speed and efficiency of their transformation by unconventional yeast strains. The effect of substrate concentration on the conversion efficiency in the culture of the [...] Read more.

We describe the impact of the number and location of methoxy groups in the structure of chalcones on the speed and efficiency of their transformation by unconventional yeast strains. The effect of substrate concentration on the conversion efficiency in the culture of the Yarrowia lipolytica KCh 71 strain was tested. In the culture of this strain, monomethoxychalcones (2′-hydroxy-2″-, 3″- and 4″-methoxychalcone) were effectively hydrogenated at over 40% to the specific dihydrochalcones at a concentration of 0.5 g/L of medium after just 1 h of incubation. A conversion rate of over 40% was also observed for concentrations of these compounds of 1 g/L of medium after three hours of transformation. As the number of methoxy substituents increases in the chalcone substrate, the rate and efficiency of transformation to dihydrochalcones decreased. The only exception was 2′-hydroxy-2″,5″-dimethoxychalcone, which was transformed into dihydrochalcone by strain KCh71 with a yield comparable to that of chalcone containing a single methoxy group. Full article

(This article belongs to the Special Issue Catalysis in the Synthesis of Biologically Active Compounds)

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12 pages, 5623 KiB

Open AccessArticle

Characterization and Catalytic-Site-Analysis of an Aldo-Keto Reductase with Excellent Solvent Tolerance

by Rui Pei, Weiliang Wu, Yuqian Zhang, Libing Tian, Wei Jiang and Shu-Feng Zhou

Catalysts 2020, 10(10), 1121; https://doi.org/10.3390/catal10101121 - 01 Oct 2020

Cited by 8 | Viewed by 2225

Abstract

Aldo-keto reductases (AKRs) mediated stereoselective reduction of prochiral carbonyl compounds is an efficient way of preparing single enantiomers of chiral alcohols due to their high chemo-, enantio-, and regio-selectivity. To date, the application of AKRs in the asymmetric synthesis of chiral alcohols has [...] Read more.

Aldo-keto reductases (AKRs) mediated stereoselective reduction of prochiral carbonyl compounds is an efficient way of preparing single enantiomers of chiral alcohols due to their high chemo-, enantio-, and regio-selectivity. To date, the application of AKRs in the asymmetric synthesis of chiral alcohols has been limited, due to the challenges of cloning and purifying. In this work, the aldo-keto reductase (AKR3-2-9) from Bacillus sp. was obtained, purified and proved to be NADPH-dependent. It exhibits good bioactivity and stability at 37 °C, pH 6.0. AKR3-2-9 is catalytically active on 11 pairs of substrates such as 3-methylcyclohexanone and methyl pyruvate, among which it showed the highest catalytic activity for acetylacetone. In addition, AKR3-2-9 was able to be resistant to five common organic solvents such as methanol and ethanol, it retained high catalytic activity even in a reaction system containing 10% v/v organic solvent for 6 h, which indicates its broad substrate spectrum and exceptional organic solvent tolerance. Furthermore, its three-dimensional structure was constructed and catalytic-site-analysis of the enzyme was conducted. Notably, it was capable of catalyzing the reaction of the key intermediates of duloxetine. The extensive substrate spectrum and predominant organic solvents resistance makes AK3-2-9 a promising enzyme which can be potentially applied in medicine synthesis. Full article

(This article belongs to the Special Issue Catalysis in the Synthesis of Biologically Active Compounds)

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