Biotransformation of adrenosterone by filamentous fungus, Cunninghamella elegans

Choudhary, M. Iqbal; Khan, Niaz Ali; Musharraf, Syed Ghulam; Anjum, Shazia; Atta-ur-Rahman, _

doi:10.1016/j.steroids.2007.08.002

Cited by 49 publications

(27 citation statements)

References 20 publications

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“…The mycelia were then transferred to sterile physiological saline solution (1 plate of mycelia per 5 mL) and homogenized for 5 min. Approximately 1.5 mL aliquots of the homogenate were inoculated into 100 mL growth media, prepared according to the methods in [42], in 250 mL Erlenmeyer flasks. The cultures were incubated for 48 h at 26 °C and 180 rpm on an Infors HT Multitron rotary shaker (In vitro Technologies, Noble Park North, VIC, Australia).…”

Section: Biotransformation By Fungus and Sample Preparationmentioning

confidence: 99%

Metabolic Profile of Synthetic Cannabinoids 5F-PB-22, PB-22, XLR-11 and UR-144 by Cunninghamella elegans

Watanabe

Kuzhiumparambil

Nguyen

et al. 2017

AAPS J

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The knowledge of metabolic profile of synthetic cannabinoids is important for the detection of the drugs in urinalysis due to the typical absence or low abundance of parent cannabinoids in human urine. The fungus Cunninghamella elegans has been reported to be a useful tool for metabolism study and thus applicability to synthetic cannabinoids metabolism was examined. In this study, 8-quinolinyl 1-(5-fluoropentyl)-1H-indole-3-carboxylate (5F-PB-22), 8-quinolinyl 1-pentyl-1H-indole-3-carboxylate (PB-22), [1-(5-fluoropentyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone (XLR-11) and (1-pentyl-1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl)methanone (UR-144) were incubated with Cunninghamella elegans and the metabolites were identified using liquid chromatographyquadrupole time-of-flight mass spectrometry. The obtained metabolites were compared with reported human metabolites to assess the suitability of the fungus to extrapolate human metabolism. 5F-PB-22 underwent, dihydroxylation, dihydrodiol formation, oxidative defluorination, oxidative defluorination to carboxylic acid, ester hydrolysis and glucosidation, alone and/or in combination. The metabolites of PB-22 were generated by hydroxylation, dihydroxylation, trihydroxylation, dihydrodiol formation, ketone formation, carboxylation, ester hydrolysis and glucosidation, alone and/or in combination. XLR-11 was transformed through hydroxylation, dihydroxylation, aldehyde formation, carboxylation, oxidative defluorination, oxidative defluorination to carboxylic acid and glucosidation, alone and/or in combination. UR-144 was metabolised by hydroxylation, dihydroxylation, trihydroxylation, aldehyde formation, ketone formation, carboxylation, N-dealkylation and combinations. These findings were consistent with previously reported human metabolism except for the small extent of ester hydrolysis observed and absence of glucuronidation. Despite the limitations, Cunninghamella elegans demonstrated the capacity to produce a wide variety of metabolites including some major human metabolites of XLR-11 and UR-144 at high abundance, showing the potential for metabolism of newly emerging synthetic cannabinoids.

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Section: Biotransformation By Fungus and Sample Preparationmentioning

confidence: 99%

Metabolic Profile of Synthetic Cannabinoids 5F-PB-22, PB-22, XLR-11 and UR-144 by Cunninghamella elegans

Watanabe

Kuzhiumparambil

Nguyen

et al. 2017

AAPS J

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“…10,11 Compound 1 was earlier subjected to microbial transformation, and several new analogues were obtained. 12 In continuation of our research on biotransformation of bioactive compounds, and drug molecules, [13][14][15] mestanolone (1) was incubated with Macrophomina phaseolina, and Cunninghamella blakesleeana, which yielded metabolites 2-8 ( Fig. 1 and 2).…”

Section: -9mentioning

confidence: 99%

Microbial transformation of mestanolone byMacrophomina phaseolinaandCunninghamella blakesleeanaand anticancer activities of the transformed products

et al. 2018

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The microbial transformation of anabolic androgenic steroid mestanolone (1) with Macrophomina phaseolina and Cunninghamella blakesleeana has afforded seven metabolites. The structures of these metabolites were characterized as 17b-hydroxy-17a-methyl-5a-androsta-1-ene-3,11-dione (2), 14a,17b-dihydroxy-17a-methyl-5a-androstan-3,11-dione (3), 17b-hydroxy-17a-methyl-5a-androstan-1,14-diene-3,11-dione (4), 17b-hydroxy-17a-methyl-5a-androstan-3,11-dione (5), 11b,17b-dihydroxy-17a-methyl-5a-androstan-1-ene-3-one (6), 9a,11b,17b-trihydroxy-17a-methyl-5a-androstan-3-one (7), and 1b,11a,17b-trihydroxy-17a-methyl-5a-androstan-3-one (8). All the metabolites, except 5 and 6, were identified as new compounds. Substrate 1 (IC 50 ¼ 27.6 AE 1.1 mM), and its metabolites 2 (IC 50 ¼ 19.2 AE 2.9 mM) and 6 (IC 50 ¼ 12.8 AE 0.6 mM) exhibited moderate cytotoxicity against the HeLa cancer cell line (human cervical carcinoma). All metabolites were noncytotoxic to 3T3 (mouse fibroblast) and H460 (human lung carcinoma) cell lines. The metabolites were also evaluated for immunomodulatory activity, and all were found to be inactive. IntroductionBiotransformation has been widely used in organic chemistry for stereoslective synthesis.1-6 Biotransformation reactions can be achieved by a variety of agents, such as enzymes, animals and plant cell cultures, and microorganisms; however, microorganisms are most effectively used for this purpose. Microbial enzyme systems can be used for reduction, oxidation, hydroxylation, and Michael addition. Regio-and stereo-selective oxidation and hydroxylation of steroids have been extensively achieved through microbial transformation. The cytochrome P450 monooxygenase system, present in microorganismsparticularly in fungi -is responsible for the stereoselective hydroxylation at various sites of the steroidal skeleton. 7-9Mestanolone (1) (C 20 H 18 O 2 ) is a member of the anabolicandrogenic class of steroids. It is weakly anabolic and strongly androgenic. Mestanolone was rst synthesized by the oxidation of 17b-methylandrostan-3b,17b-diol. It is used as a starting material for the synthesis of other anabolic steroids, such as 17-methyl-1-testosterone, and oxandrolone.10,11 Compound 1 was earlier subjected to microbial transformation, and several new analogues were obtained. 12In continuation of our research on biotransformation of bioactive compounds, and drug molecules, 13-15 mestanolone (1) was incubated with Macrophomina phaseolina, and Cunninghamella blakesleeana, which yielded metabolites 2-8 ( Fig. 1 and 2). ExperimentalGeneral Mestanolone (1) was acquired from Hangzhu Dayangchem (Cat no. 541-11-9, China). Sabouraud dextrose agar (SDA) was purchased from Merck KGaA (Cat no. 146392, Germany). Silica gel precoated TLC plates (PF 254 , Merck KGaA, Germany) were used for thin layer chromatography; phosphomolybdic acid solution was used as a staining reagent for UV inactive compounds. Silica gel (70-230 mesh, Merck, Germany) was used for column chromatography. Final purication of the compounds was carried out...

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“…Microbial transformation of steroids has been extensively investigated (Donova, Egorova, 2012), and various hydroxylated derivatives have been produced on large scale (Abourashed, Clark, Hufford, 1999). Microbial transformation of steroids has been extensively employed for the synthesis of steroidal drugs, both at laboratory and industrial levels Choudhary et al, 2011;Choudhary et al, 2010;Al-Aboudi et al, 2009;Choudhary et al, 2009;Choudhary et al, 2007;Devkota et al, 2007). In modern drug discovery process, generation of libraries 904 of bioactive compounds with diverse structures plays an important role (Tong, Dong, 2009).…”

Section: Introductionmentioning

confidence: 99%

Microbial biotransformation of beclomethasone dipropionate by Aspergillus niger

Ahmad

Khaliq

Madni

et al. 2014

Braz. J. Pharm. Sci.

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In the present research, the steroidal anti-asthmatic drug beclomethasone dipropionate was subjected to microbial biotransformation by Aspergillus niger. Beclomethasone dipropionate was transformed into various metabolites first time from microbial transformation. New drug metabolites produced can act as new potential drug molecules and can replace the old drugs in terms of safety, efficacy, and least resistance. They were purified by preparative thin layer chromatography technique, and their structures were elucidated using modern spectroscopic techniques, such as 13 C NMR, 1 H NMR, HMQC, HMQC, COSY, and NOESY, and mass spectrometry, such as EI-MS. Four metabolites were purified: (i) beclomethasone 17-monopropionate, (ii) beclomethasone 21-monopropionate, (iii) beclomethasone, and (iv) 9beta,11beta-epoxy-17,21-dihydroxy-16beta-methylpregna-1,4-diene-3,20-dione 21-propionate.Uniterms: Anti-asthmatics. Aspergillus niger/use in biotransformation. Beclomethasone dipropionate/ microbial biotransformation. Steroids/microbial transformation. Biotransformation.Na pesquisa presente o fármaco esteróide antiasmático dipropionato de beclometasona foi submetido à biotransformação microbiana pelo Aspergillus niger. O dipropionato de beclometasona foi transformado, pela primeira vez, em metabólitos variados por biotransformação microbiana. Novos metabólitos do fármaco produzidos podem agir como novas moléculas potenciais e podem substituir os fármacos antigos em questão de segurança, eficácia e mínima resistência. Eles foram purificados por cromatografia em camada delgada preparativa e as suas estruturas foram elucidadas usando técnicas espectroscópicas modernas, como 13 C NMR, 1 H NMR; HMQC; HMQC; COSY, NOESY e espectrometria de massas, por exemplo, EI-MS. Purificaram-se quatro metabólitos, denominados (i) 17-monopropionato de beclometasona; (ii) 21-monopropionato de beclometasona: (iii) beclometasona e (iv) 21-propionato de 9beta,11beta-epoxi-17,21-diidroxi-16beta-metilpregna-1,4-dieno-3,20-diona.Unitermos: Antismáticos. Aspergillus niger/uso em biotransformação. Dipropionato de beclomentasona/ biotransformação microbiana. Esteróide/biotransformação microbiana. Biotransformação.

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Biotransformation of adrenosterone by filamentous fungus, Cunninghamella elegans

Cited by 49 publications

References 20 publications

Metabolic Profile of Synthetic Cannabinoids 5F-PB-22, PB-22, XLR-11 and UR-144 by Cunninghamella elegans

Metabolic Profile of Synthetic Cannabinoids 5F-PB-22, PB-22, XLR-11 and UR-144 by Cunninghamella elegans

Microbial transformation of mestanolone byMacrophomina phaseolinaandCunninghamella blakesleeanaand anticancer activities of the transformed products

Microbial biotransformation of beclomethasone dipropionate by Aspergillus niger

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