Fusarium Lini Research Articles

Bio-pesticidal, Antimicrobial, and Anti-inflammatory Potentials of n-Hexane Fraction of Zanthoxylum armatum DC and its Chemical Profiling

Zanthoxylum armatum DC, commonly known as toothache tree, is utilized for treating inflamed gums. The plant’s volatile constituent possesses a robust fragrance and contributes to its tangy taste. This study investigates the bioactivities, including bio-pesticidal, antimicrobial, and anti-inflammatory properties as well as the chemical profiling of the n-hexane fraction based on GC-MS analysis. The evaluated activities involve contact toxicity, microplate alamar blue assay, against three different insects, five bacteria, and seven fungi, and oxidative burst assay. The NIST library serves as a standard reference database for constituent identification. Remarkable insecticidal activities comparable to the standard drug permethrin were observed, particularly against Rhyzopertha dominica (100%), Tribolium castaneum (60%), and Sitophilus oryzae (50%). The fraction exhibited significant antifungal activity against Fusarium lini (85%) and notable inhibition against B. subtillis (67.27%) and S. aureus (65.25%). Potent anti-inflammatory effects were noted with an IC50 value of 11.2±1.9 μg/ml, equivalent to standard ibuprofen at various concentrations. GC-MS analysis identified twenty compounds, with major ones including trans-13-octadecenoic acid (36.08%), cis-9 hexadecenoic acid (18.66%), and 2-propenoic acid 3 phenyl methyl ester (11.08%). The diverse bioactivities observed may be attributed to the varied nature of compounds such as polyunsaturated fatty acids and their oxides. This research revealed the potential of Z. armatum as a potential bio-pesticide, anti-inflammatory, and antimicrobial agent.

Productivity of oilseed flax depending on the use of pesticides and agrochemicals in the conditions of the Lower Volga region

In the course of the research, the effect of dressing oil flax seeds (varieties VNIIMK 620 and Rucheyok) with an insect-fungicidal tank mixture on the preservation of crops from diseases and a complex of phytophages (in particular, flax flea beetles), and an increase in seed yield was revealed. The presented agrotechnical and protective measures aimed at reducing the degree of infection and spread of fusarium (Fusarium lini Boll and Fusarium spp.) of the number of flax fleas (Aphthona, family Chrysomelidae). The introduction of well-grounded methods of using fertilizers contributes not only to the growth and development of crops, increasing yields and quality of seeds, but also contributes to the preservation of soil fertility. Presowing treatment of flax seeds with an insect-fungicidal tank mixture, followed by the introduction of mineral fertilizers N60P30K30 for cultivation, not only created a better protection of crops from disease and a decrease in the damage to the crop by infection in seeds, but also had a positive effect on seed yield.

<i>Fusarium lini</i> Potential for the Biotransformation of Norandrostenedione and Evaluation of Urease and Chymotrypsin Properties of the Transformed Products

Several androgenic steroids have been biotransformed by fungi into metabolites with numerous biological properties. Incubation of norandrostenedione (1) with Fusarium lini NRRL 2204 was carried out for the first time, yielding two new metabolites, 3,7β-dihydroxy-19-norandrost-1,3,5-trien-17-one (3) and 6α,10β,17β-trihydroxy-19-nor-4-androsten-3-one (4), along with three known compounds, 3-hydroxy-19-norandrost-1,3,5-trien-17-one (2), 10β, 17β-dihydroxy-19-nor-4-androsten-3-one (5) and 10β-hydroxy-19-nor-4- androsten-3,17-dione (6). Their structures were elucidated by extensive spectroscopic analyses, including 1D-, 2D-NMR, and HR-MS experiments. Substrate 1 and its derivatives 2-6 were evaluated in vitro for their urease and chymotrypsin inhibitory properties. Compounds 2 and 3 were found to have strong urease activity with IC50 = 23.7 ± 0.17 and 10.2 ± 0.28 μm, respectively, as compared to the standard drug thiourea (IC50 = 21.6 ± 0.12 μm). Compounds 4, 5 and 6 showed good chymotrypsin activity with IC50 values of 6.4 ± 0.19, 15.6 ± 0.46 and 18.4 ± 0.65 μm, respectively, as compared to standard chymostatin with IC50 = 5.7 ± 0.14 μm. These transformed metabolites may form the basis for the future development of new drugs against ulcer, inflammation, bacterial and viral diseases.

Lawsozaheer, a new chromone produced by an endophytic fungus Paecilomyces variotii isolated from Lawsonia Alba Lam. inhibits the growth of Staphylococcus aureus

One new chromone, lawsozaheer (1), and five known compounds 4-(2-hydroxyethyl) phenol (2), viriditoxin (3), stigmasta-4,6,8(14),22-tetraen-3-one (4), β-sitosterol (5) and stigmasterol (6) were isolated from the fungal broth of Paecilomyces variotii. Their structures were elucidated using spectroscopic data. The configuration of 1 was determined by Horeau’s method. The broth extract and compound 1 showed highly selective activity against Staphylococcus aureus (NCTC 6571) bacterium with 83.19 and 84.26% inhibition respectively at 150 µg/mL, comparing well with that of standard drug ofloxacin (87.013% inhibition at 100 µg/mL). Broth extract also showed 75, and 40% inhibition of Candida albicans and Fusarium lini, respectively.

Whole-cell fungal-mediated structural transformation of anabolic drug metenolone acetate into potent anti-inflammatory metabolites

Seven new derivatives, 6α-hydroxy-1-methyl-3-oxo-5α-androst-1-en-17-yl acetate (2), 6α,17β-dihydroxy-1-methyl-3-oxo-5α-androst-1-en (3), 7β-hydroxy-1-methyl-3-oxo-5α-androst-1-en-17-yl acetate (4), 15β,20-dihydroxy-1-methyl-3-oxo-5α-androst-1-en-17-yl acetate (5), 15β-hydroxy-1-methyl-3-oxo-5α-androst-1-en-17-yl acetate (6), 12β,17β-dihydroxy-1-methyl-3-oxoandrosta-1,4-dien (11), and 7β,15β,17β-trihydroxy-1-methyl-3-oxo-5α-androst-1-en (14), along with six known metabolites, 17β-hydroxy-1-methyl-3-oxoandrosta-1,4-dien (7), 17β-hydroxy-1-methyl-3-oxo-5α-androst-1-en (8), 17β-hydroxy-1-methyl-3-oxo-5β-androst-1-en (9), 1-methyl-5β-androst-1-en-3,17-dione (10), 1-methyl-3-oxoandrosta-1,4-dien-3,17-dione (12), and 17β-hydroxy-1α-methyl-5α-androstan-3-one (13) of metenolone acetate (1), were synthesized through whole-cell biocatalysis with Rhizopus stolonifer, Aspergillus alliaceous, Fusarium lini, and Cunninghamella elegans. Atamestane (12), an aromatase inhibitor, was synthesized for the first time via F. lini-mediated transformation of 1 as the major product. Hydroxylation, dehydrogenation, and reduction were occurred during biocatalysis. Study indicated that F. lini was able to catalyze dehydrogenation reactions selectively. Structures of compounds 1–14 were determined through NMR, HRFAB-MS, and IR spectroscopic data. Compounds 1–14 were identified as non-cytotoxic against BJ human fibroblast cell line (ATCC CRL-2522). Metabolite 5 (81.0 ± 2.5%) showed a potent activity against TNF-α production, as compared to the substrate 1 (62.5 ± 4.4%). Metabolites 2 (73.4 ± 0.6%), 8 (69.7 ± 1.4%), 10 (73.2 ± 0.3%), 11 (60.1 ± 3.3%), and 12 (71.0 ± 7.2%), also showed a good inhibition of TNF-α production. Compounds 3 (IC50 = 4.4 ± 0.01 µg/mL), and 5 (IC50 = 10.2 ± 0.01 µg/mL) showed a significant activity against T-cell proliferation. Identification of selective inhibitors of TNF-α production, and T-cell proliferation is a step forward towards the development of anti-inflammatory drugs.

Macrophomina phaseolina mediated intramolecular trans-esterification of picrotoxinin and study of convulsant activity of transformed product

Picrotoxinin (1), a stable natural neurotoxin containing a highly oxygenated polycyclic rigid compound, was first isolated from berries of Anamirta cocculus (L.) Wight & Arn. (formerly known as Menispermum cocculus). The present work was aimed to study the modification of the complex polycyclic structure of picrotoxinin (1) by using microbial transformation. Initially various fungi, such as Macrophomina phaseolina, Cunninghamella blakesleeana, Aspergillus flavus, Aspergillus niger, Cephalosporium aphidicola, and Fusarium lini were screened for their ability to modify the structure of 1. Only one fungus Macrophomina phaseolina was able to catalyze the structural modification of picrotoxinin (1). The subsequent whole cell catalysis produced an intramolecular trans-esterified product 2. The structure of the transformed product was deduced by spectroscopic, and single-crystal X-ray diffraction analyses. A comparative study on convulsant activity of picrotoxinin (1) and its metabolite 2 was conducted in mice. Interestingly, metabolite 2 showed a delayed convulsant activity, as compared to the compound 1.

Bio-Catalytic Structural Transformation of Anti-cancer Steroid, Drostanolone Enanthate with Cephalosporium aphidicola and Fusarium lini, and Cytotoxic Potential Evaluation of Its Metabolites against Certain Cancer Cell Lines.

In search of selective and effective anti-cancer agents, eight metabolites of anti-cancer steroid, drostanolone enanthate (1), were synthesized via microbial biotransformation. Enzymes such as reductase, oxidase, dehydrogenase, and hydrolase from Cephalosporium aphidicola, and Fusarium lini were likely involved in the biotransformation of 1 into new metabolites at pH 7.0 and 26°C, yielding five new metabolites, 2α-methyl-3α,14α,17β-trihydroxy-5α-androstane (2), 2α-methyl-7α-hydroxy-5α-androstan-3,17-dione (3), 2-methylandrosta-11α-hydroxy-1, 4-diene-3,17-dione (6), 2-methylandrosta-14α-hydroxy-1,4-diene-3,17-dione (7), and 2-methyl-5α-androsta-7α-hydroxy-1-ene-3,17-dione (8), along with three known metabolites, 2α-methyl-3α,17β-dihydroxy-5α-androstane (4), 2-methylandrosta-1, 4-diene-3,17-dione (5), and 2α-methyl-5α-androsta-17β-hydroxy-3-one (9), on the basis of NMR, and HREI-MS data, and single-crystal X-ray diffraction techniques. Interestingly, C. aphidicola and F. lini were able to catalyze hydroxylation only at alpha positions of 1. Compounds 1–9 showed a varying degree of cytotoxicity against HeLa (human cervical carcinoma), PC3 (human prostate carcinoma), H460 (human lung cancer), and HCT116 (human colon cancer) cancer cell lines. Interestingly, metabolites 4 (IC50 = 49.5 ± 2.2 μM), 5 (IC50 = 39.8 ± 1.5 μM), 6 (IC50 = 40.7 ± 0.9 μM), 7 (IC50 = 43.9 ± 2.4 μM), 8 (IC50 = 19.6 ± 1.4 μM), and 9 (IC50 = 25.1 ± 1.6 μM) were found to be more active against HeLa cancer cell line than the substrate 1 (IC50 = 54.7 ± 1.6 μM). Similarly, metabolites 2 (IC50 = 84.6 ± 6.4 μM), 3 (IC50 = 68.1 ± 1.2 μM), 4 (IC50 = 60.4 ± 0.9 μM), 5 (IC50 = 84.0 ± 3.1 μM), 6 (IC50 = 58.4 ± 1.6 μM), 7 (IC50 = 59.1 ± 2.6 μM), 8 (IC50 = 51.8 ± 3.4 μM), and 9 (IC50 = 57.8 ± 3.2 μM) were identified as more active against PC-3 cancer cell line than the substrate 1 (IC50 = 96.2 ± 3.0 μM). Metabolite 9 (IC50 = 2.8 ± 0.2 μM) also showed potent anticancer activity against HCT116 cancer cell line than the substrate 1 (IC50 = 3.1 ± 3.2 μM). In addition, compounds 1–7 showed no cytotoxicity against 3T3 normal cell line, while compounds 8 (IC50 = 74.6 ± 3.7 μM), and 9 (IC50 = 62.1 ± 1.2 μM) were found to be weakly cytotoxic.

Fungal biotransformation of diuretic and antihypertensive drug spironolactone with Gibberella fujikuroi, Curvularia lunata, Fusarium lini, and Aspergillus alliaceus

Derivatives of spironolactone (1), a diuretic and antihypertensive drug, were synthesized by using fungal cells for the first time. Ten different fungi were screened for their ability to biotransform 1, four of which were able to produce metabolites 2–8. Gibberella fujikuroi produced canrenone (2), 1-dehydrocanrenone (3), Curvularia lunuta provided compound 2, and 7α-thio-spironolactone (4), Fusarium lini yielded compounds 2, 3, 1β-hydroxycanrenone (5), 1α-hydroxycanrenone (6), 1-dehydro-15α-hydroxycanrenone (7), and 15α-hydroxycanrenone (8), while Aspergillus alliaceus was able to produce all the seven metabolites. Metabolites 5, 6, and 7 were identified as new compounds. Their structures were elucidated by using different spectroscopic techniques. Substrate 1 and its metabolites 2, 3, and 5–8 were also evaluated for α-glucosidase inhibitory activity in vitro. Substrate 1 was found to be strongly active with IC50 = 335 ± 4.3 μM as compared to the standard drug acarbose IC50 = 840 ± 1.73 μM, whereas all of resulting metabolites were found to be inactive.

Biotransformation of anabolic compound methasterone with Macrophomina phaseolina, Cunninghamella blakesleeana, and Fusarium lini, and TNF-α inhibitory effect of transformed products

Microbial transformation of methasterone (1) was investigated with Macrophomina phaseolina, Cunninghamella blakesleeana, and Fusarium lini. Biotransformation of 1 with M. phaseolina yielded metabolite 2, while metabolites 3–7 were obtained from the incubation of 1 with C. blakesleeana. Metabolites 8–13 were obtained through biotransformation with F. lini. All metabolites, except 13, were found to be new. Methasterone (1) and its metabolites 2–6, 9, 10, and 13 were then evaluated for their immunomodulatory effects against TNF-α, NO, and ROS production. Among all tested compounds, metabolite 6 showed a potent inhibition of proinflammatory cytokine TNF-α (IC50=8.1±0.9μg/mL), as compared to pentoxifylline used as a standard (IC50=94.8±2.1μg/mL). All metabolites were also evaluated for the inhibition of NO production at concentration of 25μg/mL. Metabolites 6 (86.7±2.3%) and 13 (62.5±1.5%) were found to be the most potent inhibitors of NO as compared to the standard NG-monomethyl-l-arginine acetate (65.6±1.1%). All metabolites were found to be non-toxic against PC3, HeLa, and 3T3 cell lines. Observed inhibitory potential of metabolites 6 and 13 against pro-inflammatory cytokine TNF-α, as well as NO production makes them interesting leads for further studies.

In vitro Antimicrobial Activity of Methanolic Extract from Varthemia iphionoides Leaves

<p>In the Mediterranean region, <em>Varthemia iphionoides</em> is commonly used in folk medicine for the treatment of gastrointestinal disorders. The present study described the antimicrobial activity of the methanolic extract of <em>V.</em> <em>iphionoides</em> leaves. The extract was assayed against a panel of pathogenic bacteria and fungi using agar well diffusion method. The antibacterial activity of the methanolic extract was investigated against six standard bacterial species and was found to exhibit high antibacterial activity. The most sensitive bacterium was <em>Klebsiella pneumoniae </em>ATCC 13883 followed by <em>Proteus vulgaris</em> ATCC 13315 and methicillin-resistant <em>Staphylococcus aureus</em> ATCC 95047. The least sensitive bacterium to <em>V.</em> <em>iphionoides</em> methanolic extract was <em>Escherichia coli</em> O157:H7 ATCC43895. Antifungal susceptibility of 13 fungal species was tested against <em>V.</em> <em>iphionoides</em> methanolic extract. Among the fungal species studied, <em>Fusarium lini</em> was the most sensitive and <em>Beauveria bassiana</em> was the most resistant to the extract. Good antifungal activity has been displayed by the methanolic extract of <em>V.</em> <em>iphionoides</em> against <em>Aspergillus brasiliensis</em>,<em> Aspergillus niger</em>, and <em>Aspergillus alliaceus</em>,<em> Aspergillus flavus</em>, <em>Cunninghamella echinulata</em>, <em>Gibberella fujikuroi</em>, <em>Macrophomina phaseolina</em>, <em>Cephalosporum aphidicola</em>, <em>Rhizoupus stolonifer</em>, <em>Curvularia lunata</em> and <em>Cunninghamella elegans</em>. The observed antimicrobial potential of <em>V.</em> <em>iphionoides</em> indicated that this plant possesses bioactive compounds that are able to combat pathogenic microorganisms and support its traditional use in the treatment of pathogen infection.</p>

Epoxidation of Ferutinin by Different Fungi and Antibacterial Activity of its Metabolite

Structural transformation of the sesquiterpene ester, ferutinin (1), by suspended fungal cultures of Aspergillus niger, Rhizopus stolonifer, and Fusarium lini, resulted in the formation of a metabolite. This metabolite was identified as ferutinin α-epoxide (2), by different spectroscopic techniques. Metabolite 2 showed a good antibacterial activity against Staphylococcus aureuscompared to ferutinin (1).

Microbial transformation of anti-cancer steroid exemestane and cytotoxicity of its metabolites against cancer cell lines

BackgroundMicrobial transformation of steroids has been extensively used for the synthesis of steroidal drugs, that often yield novel analogues, not easy to obtain by chemical synthesis. We report here fungal transformation of a synthetic steroidal drug, exemestane, used for the treatment of breast cancer and function through inhibition of aromatase enzyme.ResultsMicrobial transformation of anti-cancer steroid, exemestane (1), was investigated by using two filamentous fungi. Incubation of 1 with fungi Macrophomina phaseolina, and Fusarium lini afforded three new, 11α-hydroxy-6-methylene-androsta-1, 4-diene-3,17-dione (2), 16β, 17β-dihydroxy-6-methylene-androsta-1, 4-diene-3-one (3), and 17β-hydroxy-6-methylene-androsta-1, 4-diene-3, 16-dione (4), and one known metabolites, 17β-hydroxy-6-methylene-androsta-1, 4-diene-3-one (5). Their structures were deduced spectroscopically. Compared to 1 (steroidal aromatase inactivator), the transformed metabolites were also evaluated for cytotoxic activity by using a cell viability assay against cancer cell lines (HeLa and PC3). Metabolite 2 was found to be moderately active against both the cell lines.ConclusionsBiotransformation of exemestane (1) provides an efficient method for the synthesis of new analogues of 1. The metabolites were obtained as a result of reduction of double bond and hydroxylation. The transformed product 2 exhibited a moderate activity against cancer cell lines (HeLa and PC3). These transformed products can be studied for their potential as drug candidates.

Synthesis of some potent immunomodulatory and anti-inflammatory metabolites by fungal transformation of anabolic steroid oxymetholone

BackgroundBiotransformation of organic compounds by using microbial whole cells provides an efficient approach to obtain novel analogues which are often difficult to synthesize chemically. In this manuscript, we report for the first time the microbial transformation of a synthetic anabolic steroidal drug, oxymetholone, by fungal cell cultures.ResultsIncubation of oxymetholone (1) with Macrophomina phaseolina, Aspergillus niger, Rhizopus stolonifer, and Fusarium lini produced 17β-hydroxy-2-(hydroxy-methyl)-17α-methyl-5α-androstan-1-en-3-one (2), 2α,17α-di(hydroxyl-methyl)-5α-androstan-3β,17β-diol (3), 17α-methyl-5α-androstan-2α,3β,17β-triol (4), 17β-hydroxy-2-(hydroxymethyl)-17α-methyl-androst-1,4-dien-3-one (5), 17β-hydroxy-2α-(hydroxy-methyl)-17α-methyl-5α-androstan-3-one (6), and 2α-(hydroxymethyl)-17α-methyl-5α-androstan-3β-17β-diol (7). Their structures were deduced by spectral analyses, as well as single-crystal X-ray diffraction studies. Compounds 2–5 were identified as the new metabolites of 1. The immunomodulatory, and anti-inflammatory activities and cytotoxicity of compounds 1–7 were evaluated by observing their effects on T-cell proliferation, reactive oxygen species (ROS) production, and normal cell growth in MTT assays, respectively. These compounds showed immunosuppressant effect in the T-cell proliferation assay with IC50 values between 31.2 to 2.7 μg/mL, while the IC50 values for ROS inhibition, representing anti-inflammatory effect, were in the range of 25.6 to 2.0 μg/mL. All the compounds were found to be non-toxic in a cell-based cytotoxicity assay.ConclusionMicrobial transformation of oxymetholone (1) provides an efficient method for structural transformation of 1. The transformed products were obtained as a result of de novo stereoselective reduction of the enone system, isomerization of double bond, insertion of double bond and hydroxylation. The transformed products, which showed significant immunosuppressant and anti-inflammatory activities, can be further studied for their potential as novel drugs.

Biotransformation of an antimalarial drug, artemether by plant and fungal cell cultures

Abstract Biotransformation of 1 with Fusarium lini, Macrophomina phaseolina, and plant cell suspension culture of Azadirachta indica yielded five biotransformed products with the lacking of peroxy-linkage, 9α-acetoxy, 10β-methoxyartemethin-I (2), 9α-hydroxyartemethin-II (3), 10β-hydroxyartemethin-I (4) and 3α-hydroxy,12β-methoxyartemethin-III (5) and 3α-12β-dihydroxyartemethin-III (6). Metabolites 2 and 5 were obtained through metabolism with A. indica culture. Metabolites 3 and 4 were found to be new compounds. Their structures were deduced by spectroscopic techniques while single-crystal X-ray diffraction technique was used for the unambiguous characterization of compounds 2, 3 and 6. All biotransformed products were evaluated by in vitro antimalarial assay.

Biotransformation of 11-ketoprogesterone by Filamentous Fungus, <i>Fusarium lini</i>

Microbial transformation of 11-ketoprogesterone (1) by the filamentous fungi Fusarium lini was investigated. Biotransformation of 1 with F. lini resulted in the production of ten oxidative metabolites (2-11). Structures of these metabolites were deduced by spectroscopic analysis and seven of them, 5-11, were found to be new metabolites.Keywords: 11-Ketoprogesterone; Steroid; Microbial transformation; Hydroxylation; Filamentous fungi; Fusarium lini.© 2011 JSR Publications. ISSN: 2070-0237 (Print); 2070-0245 (Online). All rights reserved. doi:10.3329/jsr.v2i2.6221 J. Sci. Res. 3 (2), 347-356 (2011)

Microbial Transformations of (+)-Isomenthol by Fusarium lini and Rhizopus stolonifer

Microbial transformation of (+)-isomenthol (1) by various strains of fungi was investigated. Fusarium lini has successfully converted compound 1 into a new metabolite, 5α-hydroxyisomenthol (2), and a known metabolite, 1α-hydroxyisomenthol (3), whereas incubation with Rhizopus stolonifer only yielded metabolite 3. The transformed metabolites were structurally characterized on the basis of their spectral data.

Microbial transformation of 18β-glycyrrhetinic acid by Cunninghamella elegans and Fusarium lini, and lipoxygenase inhibitory activity of transformed products

The microbial transformation of 18β-glycyrrhetinic acid (1) by Cunninghamella elegans afforded a metabolite, 3β,7β-dihydroxy-11-oxo-olean-12-en-30-oic acid (2), while fermentation of 1 with Fusarium lini afforded a metabolite, 3,11-dioxo-olean-12-en-30-oic acid (3). Compound 3 exhibited a potent lipoxygenase (LOX) inhibitory activity. The structures of these metabolites were elucidated on the basis of spectroscopic techniques.

Microbial transformation of testosterone by Rhizopus stolonifer and Fusarium lini

The microbial transformation of testosterone by the fungi Rhizopus stolonifer and Fusarium lini has been investigated for the first time. The bioconversion reactions observed from R. stolonifer included oxidation of a 17β-hydroxyl group, a hydroxylation at equatorial 11α position, reduction of the double bond at C-4 with oxidation of the methylene at C-6 to the corresponding keto group, and lactonisation of ring D; the latter is the first report of this reaction by a Rhizopus species. Fusarium lini promoted 1-dehydrogenation of the steroid, which has been rarely observed in fungi cultures. The other routes of biotransformations included oxidation of the 17β-hydroxyl group and the hydroxylation at 11α position. These reactions are not common for Fusarium species.

Microbial transformation of oleanolic acid by Fusarium lini and α-glucosidase inhibitory activity of its transformed products

The biotransformation of a pentacyclic triterpene, oleanolic acid (1), with Fusarium lini afforded two oxidative metabolites, 2α,3β-dihydroxyolean-12-en-28-oic acid (2), and 2α,3β,11β-trihydroxyolean-12-en-28-oic acid (3). Metabolite 3 was found to be a new compound. The structures were characterized on the basis of spectroscopic studies. These metabolites exhibited a potent inhibition of α-glucosidase enzyme.

Fungal Transformation of Dydrogesterone and Inhibitory Effect of Its Metabolites on the Respiratory Burst in Human Neutrophils

The biotransformation of the synthetic hormone dydrogesterone (1) by a number of fungal strains - including Cephalosporium aphidicola, Rhizopus stolonifer, Cunninghamella elegans, and Fusarium lini - afforded ten different metabolites, compounds 2-11. From a structural point of view, these transformations involved a combination of hydroxylation, oxidation, reduction, and/or epoxidation. The pregnane-based metabolites 10 and 11 are new compounds. All the known compounds were obtained for the first time from 1 by fungal transformation. The metabolites 3, 5, and 8 showed more-potent respiratory-burst inhibitory activity than the substrate 1 in a neutrophil-based cellular assay (Table 3).