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13 pages, 1476 KiB

Open AccessArticle

Microbial Modifications of Androstane and Androstene Steroids by Penicillium vinaceum

by Anna Panek, Paulina Łyczko and Alina Świzdor

Molecules 2020, 25(18), 4226; https://doi.org/10.3390/molecules25184226 - 15 Sep 2020

Cited by 7 | Viewed by 3000

Abstract

The biotransformation of steroid compounds is a promising, environmentally friendly route to new pharmaceuticals and hormones. One of the reaction types common in the metabolic fate of steroids is Baeyer-Villiger oxidation, which in the case of cyclic ketones, such as steroids, leads to [...] Read more.

The biotransformation of steroid compounds is a promising, environmentally friendly route to new pharmaceuticals and hormones. One of the reaction types common in the metabolic fate of steroids is Baeyer-Villiger oxidation, which in the case of cyclic ketones, such as steroids, leads to lactones. Fungal enzymes catalyzing this reaction, Baeyer-Villiger monooxygenases (BVMOs), have been shown to possess broad substrate scope, selectivity, and catalytic performance competitive to chemical oxidation, being far more environmentally green. This study covers the biotransformation of a series of androstane steroids (epiandrosterone and androsterone) and androstene steroids (progesterone, pregnenolone, dehydroepiandrosterone, androstenedione, 19-OH-androstenedione, testosterone, and 19-nortestosterone) by the cultures of filamentous fungus Penicillium vinaceum AM110. The transformation was monitored by GC and the resulting products were identified on the basis of chromatographic and spectral data. The investigated fungus carries out effective Baeyer-Villiger oxidation of the substrates. Interestingly, introduction of the 19-OH group into androstenedione skeleton has significant inhibitory effect on the BVMO activity, as the 10-day transformation leaves half of the 19-OH-androstenedione unreacted. The metabolic fate of epiandrosterone and androsterone, the only 5α-saturated substrates among the investigated compounds, is more complicated. The transformation of these two substrates combined with time course monitoring revealed that each substrate is converted into three products, corresponding to oxidation at C-3 and C-17, with different time profiles and yields. Full article

(This article belongs to the Special Issue Steroids-II)

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14 pages, 2072 KiB

Open AccessArticle

Detection of 7-Dehydrocholesterol and Vitamin D3 Derivatives in Honey

by Tae-Kang Kim, Venkatram Atigadda, Pawel Brzeminski, Adrian Fabisiak, Edith K. Y. Tang, Robert C. Tuckey and Andrzej T. Slominski

Molecules 2020, 25(11), 2583; https://doi.org/10.3390/molecules25112583 - 2 Jun 2020

Cited by 29 | Viewed by 11501

Abstract

20(S)-Hydroxyvitamin D3 (20(OH)D3) is an endogenous metabolite produced by the action of CYP11A1 on the side chain of vitamin D3 (D3). 20(OH)D3 can be further hydroxylated by CYP11A1, CYP27A1, CYP24A1 and/or CYP27B1 to several hydroxyderivatives. CYP11A1 also hydroxylates D3 to 22-monohydroxyvitamin [...] Read more.

20(S)-Hydroxyvitamin D3 (20(OH)D3) is an endogenous metabolite produced by the action of CYP11A1 on the side chain of vitamin D3 (D3). 20(OH)D3 can be further hydroxylated by CYP11A1, CYP27A1, CYP24A1 and/or CYP27B1 to several hydroxyderivatives. CYP11A1 also hydroxylates D3 to 22-monohydroxyvitamin D3 (22(OH)D3), which is detectable in the epidermis. 20-Hydroxy-7-dehydrocholesterol (20(OH)-7DHC) has been detected in the human epidermis and can be phototransformed into 20(OH)D3 following the absorption of ultraviolet B (UVB) energy by the B-ring. 20(OH)D3 and its hydroxyderivatives have anti-inflammatory, pro-differentiation and anti-proliferative effects, comparable to 1,25-dihydroxyvitamin D3 (1,25(OH)₂D3). Since cytochromes P450 with 20- or 25-hydroxylase activity are found in insects participating in ecdysone synthesis from 7-dehydrocholesterol (7DHC), we tested whether D3-hydroxyderivatives are present in honey, implying their production in bees. Honey was collected during summer in the Birmingham area of Alabama or purchased commercially and extracted and analyzed using LC-MS. We detected a clear peak of m/z = 423.324 [M + Na]⁺ for 20(OH)D3 corresponding to a concentration in honey of 256 ng/g. We also detected peaks of m/z = 383.331 [M + H − H₂O]⁺ for 20(OH)-7DHC and 25(OH)D3 with retention times corresponding to the standards. We further detected species with m/z = 407.329 [M + Na]⁺ corresponding to the RT of 7DHC, D3 and lumisterol3 (L3). Similarly, peaks with m/z = 399.326 [M + H − H₂O]⁺ were detected at the RT of 1,25(OH)₂D3 and 1,20-dihydroxyvitamin D3 (1,20(OH)₂D3). Species corresponding to 20-monohydroxylumisterol3 (20(OH)L3), 22-monohydroxyvitamin D3 (22(OH)D3), 20,23-dihydroxyvitamin D3 (20,23(OH)₂D3), 20,24/25/26-dihydroxyvitamin D3 (20,24/25/26(OH)₂D3) and 1,20,23/24/25/26-trihydroxyvitamin D3 (1,20,23/24/25/26(OH)₃D3) were not detectable above the background. In conclusion, the presence of 7DHC and D3 and of species corresponding to 20(OH)-7DHC, 20(OH)D3, 1,20(OH)₂D3, 25(OH)D3 and 1,25(OH)₂D3 in honey implies their production in bees, although the precise biochemistry and photochemistry of these processes remain to be defined. Full article

(This article belongs to the Special Issue Steroids-II)

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13 pages, 1274 KiB

Open AccessArticle

A Convenient Synthesis of (16S,20S)-3β-Hydroxy-5α-pregnane-20,16-carbolactam and Its N-alkyl Derivatives

by Agnieszka Wojtkielewicz, Damian Pawelski, Przemysław Bazydło, Aneta Baj, Stanisław Witkowski and Jacek W. Morzycki

Molecules 2020, 25(10), 2377; https://doi.org/10.3390/molecules25102377 - 20 May 2020

Cited by 1 | Viewed by 3364

Abstract

A concise synthesis of (16S,20S)-3β-hydroxy-5α-pregnane-20,16-carbolactam from tigogenin via the corresponding lactone is described. The most efficient synthetic route consisted of the lactone ring-opening with aminoalane reagent followed by PDC or Dess-Martin oxidation. The oxo-amide obtained was subjected to cyclization [...] Read more.

A concise synthesis of (16S,20S)-3β-hydroxy-5α-pregnane-20,16-carbolactam from tigogenin via the corresponding lactone is described. The most efficient synthetic route consisted of the lactone ring-opening with aminoalane reagent followed by PDC or Dess-Martin oxidation. The oxo-amide obtained was subjected to cyclization with Et₃SiH/TFA or Et₃SiH/Bi(TfO)₃. Alternately, the lactone was converted first to the oxo-acid, which was then subjected to the microwave-assisted reductive amination. N-Alkyl derivatives were also obtained in a similar way. Full article

(This article belongs to the Special Issue Steroids-II)

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9 pages, 871 KiB

Open AccessArticle

Simple Synthesis of 17-β-O-hemisuccinate of Stanozolol for Immunoanalytical Methods

by Silvana Casati, Roberta Ottria and Pierangela Ciuffreda

Molecules 2020, 25(9), 2019; https://doi.org/10.3390/molecules25092019 - 26 Apr 2020

Cited by 3 | Viewed by 3166

Abstract

The use of doping in sports is a global problem that affects athletes around the world. Among the different methods developed to detect doping agents in biological samples, there are antibody-based methods that need an appropriate hapten design. Steroids with a hydroxyl group [...] Read more.

The use of doping in sports is a global problem that affects athletes around the world. Among the different methods developed to detect doping agents in biological samples, there are antibody-based methods that need an appropriate hapten design. Steroids with a hydroxyl group can be converted to the corresponding hemisuccinates. A novel approach to the synthesis of 17β-O-hemisuccinate of the common doping agent stanozolol is described here. Acylation of stanozolol with methyl 4-chloro-4-oxobutyrate/4-dimethylaminopyridine, followed by mild alkaline hydrolysis with methanolic sodium hydroxide at room temperature, gave the simultaneous protection and deprotection of pyrazole-nitrogen atoms. The proposed new synthetic method allows the desired hemisuccinate derivative to be obtained in only two steps, and with a good total yield starting from stanozolol. Full article

(This article belongs to the Special Issue Steroids-II)

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15 pages, 3455 KiB

Open AccessArticle

Relation between Crystal Structures of Precursors and Final Products: Example of Vitamin D Intermediates

by Monika Wanat, Maura Malinska, Andrzej Kutner and Krzysztof Woźniak

Molecules 2020, 25(8), 1802; https://doi.org/10.3390/molecules25081802 - 14 Apr 2020

Cited by 2 | Viewed by 2993

Abstract

In this paper, we proved that the solid-state structure of vitamin D analog is well represented by the structures of its structural fragments. This is important in predicting the biological activity of vitamin D analogs that are not available in the solid form. [...] Read more.

In this paper, we proved that the solid-state structure of vitamin D analog is well represented by the structures of its structural fragments. This is important in predicting the biological activity of vitamin D analogs that are not available in the solid form. The previously published crystal structure of advanced vitamin D intermediate provided additional insights into vitamin D properties. A similar analysis based on simple vitamin D intermediate analogues showed that precursors crystallized in the space groups typical for vitamins D; geometrical parameters were related to the corresponding parameters in the vitamin D analogues; and crystal structures of the basic intermediates and their final products contained similar intermolecular interactions, essential for the infinite hydrogen bond motif observed in the vitamin D analogues. The energy of these interactions is related as shown by theoretical calculations, that is, energy frameworks analysis. Moreover, analysis of the hydrogen bonds motifs revealed a relation between these motifs and the absolute configuration of basic intermediates as well as the space orientation of the exocyclic methylene group in the final structures. Full article

(This article belongs to the Special Issue Steroids-II)

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15 pages, 982 KiB

Open AccessFeature PaperArticle

Synthesis of New Cisplatin Derivatives from Bile Acids

by Barbara Seroka, Zenon Łotowski, Agnieszka Hryniewicka, Lucie Rárová, Rafal R. Sicinski, Aneta M. Tomkiel and Jacek W. Morzycki

Molecules 2020, 25(3), 655; https://doi.org/10.3390/molecules25030655 - 4 Feb 2020

Cited by 7 | Viewed by 3976

Abstract

A series of bile acid derived 1,2- and 1,3-diamines as well as their platinum(II) complexes were designed and synthesized in hope to get a highly cytotoxic compound by the combination of two bioactive moieties. All complexes obtained were subjected to cytotoxicity assays in [...] Read more.

A series of bile acid derived 1,2- and 1,3-diamines as well as their platinum(II) complexes were designed and synthesized in hope to get a highly cytotoxic compound by the combination of two bioactive moieties. All complexes obtained were subjected to cytotoxicity assays in vitro and some hybrid molecules showed an expected activity. Full article

(This article belongs to the Special Issue Steroids-II)

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8 pages, 1200 KiB

Open AccessArticle

Two-step Synthesis of Solasodine Pivalate from Diosgenin Pivalate

by Agnieszka Wojtkielewicz, Urszula Kiełczewska and Jacek W. Morzycki

Molecules 2019, 24(6), 1132; https://doi.org/10.3390/molecules24061132 - 21 Mar 2019

Cited by 5 | Viewed by 3463

Abstract

A two-step synthesis of solasodine pivalate from diosgenin pivalate is described. The key transformation involves the reaction of diosgenin pivalate with benzyl carbamate (CbzNH₂) promoted by TMSOTf. During the reaction the F-ring of the spiroketal moiety opens up with a simultaneous [...] Read more.

A two-step synthesis of solasodine pivalate from diosgenin pivalate is described. The key transformation involves the reaction of diosgenin pivalate with benzyl carbamate (CbzNH₂) promoted by TMSOTf. During the reaction the F-ring of the spiroketal moiety opens up with a simultaneous introduction of a Cbz-protected amino group in position 26. A one-pot deprotection of 26-amine with AcBr/BuOH followed by the N-cyclization affords solasodine pivalate in 45% overall yield. Full article

(This article belongs to the Special Issue Steroids-II)

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12 pages, 1452 KiB

Open AccessArticle

Simple and Accurate HPTLC-Densitometric Method for Assay of Nandrolone Decanoate in Pharmaceutical Formulation

by Małgorzata Dołowy, Alina Pyka-Pająk and Josef Jampílek

Molecules 2019, 24(3), 435; https://doi.org/10.3390/molecules24030435 - 25 Jan 2019

Cited by 7 | Viewed by 3880

Abstract

This study reports the development and validation of a new, simple, and accurate high-performance thin-layer chromatography (HPTLC)-densitomeric method for the determination of nandrolone decanoate in a commercially available injection formulation. Chromatographic analysis was performed on glass CN modified silica gel 60F₂₅₄ plates [...] Read more.

This study reports the development and validation of a new, simple, and accurate high-performance thin-layer chromatography (HPTLC)-densitomeric method for the determination of nandrolone decanoate in a commercially available injection formulation. Chromatographic analysis was performed on glass CN modified silica gel 60F₂₅₄ plates developed using n-hexane-ethyl acetate in volume ratio 42.5:7.5 as the mobile phase. Densitometric scanning was carried out at the wavelength of 245 nm. This chromatographic system gave compact spot and a symmetrical peak of nandrolone decanoate with retardation factor (R_F) value at 0.57 (±0.02). The linearity of this method with the high correlation coefficient of calibration plot ranges from 0.780 to 12.500 μg/spot. The developed method is characterized by good precision (coefficient of variation CV < 2%) and high accuracy close to 100.3% (R = 99.0%). Values of limits of detection and quantification equal to 0.231 and 0.700 μg/spot, respectively, confirm the sensitivity of the developed method. The analysis of the pharmaceutical formulation of nandrolone decanoate indicates drug content of 50.5 mg/mL and 101.0% in relation to the label claim. This is in good agreement with the recommendation of the International Council for Harmonisation (ICH) guidelines as well as the pharmacopoeial requirements. The low CV value (<1%) of nandrolone decanoate content in the tested injection formulation confirms the suitability of the proposed HPTLC-densitometric method for routine control of this compound in examined pharmaceuticals. Full article

(This article belongs to the Special Issue Steroids-II)

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Review

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19 pages, 1906 KiB

Open AccessFeature PaperReview

Glucocorticoids Influencing Wnt/β-Catenin Pathway; Multiple Sites, Heterogeneous Effects

by Katalin Meszaros and Attila Patocs

Molecules 2020, 25(7), 1489; https://doi.org/10.3390/molecules25071489 - 25 Mar 2020

Cited by 22 | Viewed by 5444

Abstract

Glucocorticoid hormones are vital; their accurate operation is a necessity at all ages and in all life situations. Glucocorticoids regulate diverse physiological processes and they use many signaling pathways to fulfill their effect. As the operation of these hormones affects many organs, the [...] Read more.

Glucocorticoid hormones are vital; their accurate operation is a necessity at all ages and in all life situations. Glucocorticoids regulate diverse physiological processes and they use many signaling pathways to fulfill their effect. As the operation of these hormones affects many organs, the excess of glucocorticoids is actually detrimental to the whole human body. The endogenous glucocorticoid excess is a relatively rare condition, but a significant proportion of adult people uses glucocorticoid medication for the treatment of chronic illnesses, therefore they are exposed to the side effects of long-term glucocorticoid treatment. Our review summarizes the adverse effects of glucocorticoid excess affecting bones, adipose tissue, brain and skin, focusing on those effects which involve the Wnt/β-catenin pathway. Full article

(This article belongs to the Special Issue Steroids-II)

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