Microbial transformation of danazol with Cunninghamella blakesleeana and anti-cancer activity of danazol and its transformed products

Baydoun, Elias; Wahab, Atia‐tul; Mehmood, Hina; Ahmad, Malik Shoaib; Malik, Rehan; Smith, Colin A.; Choudhary, M. Iqbal

doi:10.1016/j.steroids.2015.11.010

Cited by 12 publications

(9 citation statements)

References 23 publications

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“…A modern synthetic strategy for producing new natural products consists on biotransformation, due to its capacity to introduce functional groups in different positions of carbon skeleton, thus improving pharmacological properties of target compounds (Yang et al 2015). In fungi, there is a large variety of enzymes, which have been proved to be useful for biocatalytic processes, catalyzing many chemical reactions, including oxidations, hydroxylations, and reductions among others (Baydoun et al 2016). Besides, this methodology presents regio-and stereo-selectivity due to the chiral nature of enzymes and can be accomplished at room temperature, under neutral aqueous conditions.…”

Section: Introductionmentioning

confidence: 99%

A New Acetylcholinesterase Inhibitor from Green Glycosylation of Trachyloban-19-oic Acid by Mucor plumbeus

Santos

Takahashi

2017

An. Acad. Bras. Ciênc.

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The in vitro metabolism of a widespread natural product, trachyloban-19-oic acid (1), by the fungal species Mucor plumbeus was studied in a sucrose-yeast liquid medium. Two products were isolated, and their structures were determined by spectroscopic means as 7β-hydroxytrachyloban-19-oic acid (5) and trachyloban-19-O-β-D-glucopyranosyl ester (6). To the best of our knowledge, compound 6 is herein reported by the first time in the literature. These compounds were assayed for acetylcholinesterase inhibition along with some related compounds. Compound 6 showed the highest acetylcholinesterase inhibitory activity at 10000 µg/mL among the tested compounds, a result (92.89%) comparable to the activity of the positive control, galanthamine (94.21%). Therefore, biotransformation of the natural product 1 by M. plumbeus produced a novel compound with potential as a new lead to develop anti-Alzheimer medicines.

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Section: Introductionmentioning

confidence: 99%

A New Acetylcholinesterase Inhibitor from Green Glycosylation of Trachyloban-19-oic Acid by Mucor plumbeus

Santos

Takahashi

2017

An. Acad. Bras. Ciênc.

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“…The hydroxylation abilities of nine microorganisms from the genera Cunninghamella and Mucor was evaluated, because previous studies have shown that species in these two genera are rich in hydroxylases [27]. Additionally, C. elegans , C. echinulata , C.blakesleeana, and M. circinelloides have been successfully employed to hydroxylate other substrates [28,29,30]. The hydroxylation ability of these microorganisms was estimated by identifying and comparing their hydroxylation products.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Microbial Transformation of 10-deoxoartemisinin by UPLC-ESI-Q-TOF-MSE

et al. 2019

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10-deoxoartemisinin is a semisynthetic derivative of artemisinin that lacks a lactone carbonyl group at the 10-position, and has stronger antimalarial properties than artemisinin. However, 10-deoxoartemisinin has limited utility as a therapeutic agent because of its low solubility and bioavailability. Hydroxylated 10-deoxoartemisinins are a series of properties-improved derivatives. Via microbial transformation, which can hydroxylate 10-deoxoartemisinin at multiple sites, the biotransformation products of 10-deoxoartemisinin have been investigated in this paper. Using ultra-performance liquid chromatography-electrospray ionization-quadrupole time-of-flight mass spectrometry (UPLC-ESI-Q-TOF-MSE) combined with UNIFI software, products of microbial transformation of 10-deoxoartemisinin were rapidly and directly analyzed. The hydroxylation abilities of nine microorganisms were compared using this method. All of the microorganisms evaluated were able to hydroxylate 10-deoxoartemisinin, and a total of 35 hydroxylated products were identified. These can be grouped into dihydroxylated 10-deoxoartemisinins, monohydroxylated 10-deoxoartemisinins, hydroxylated dehydrogenated 10-deoxoartemisinins, and hydroxylated hydrogenated 10-deoxoartemisinins. Cunninghamella echinulata and Cunninghamella blakesleeana are able to hydroxylate 10-deoxoartemisinin, and their biotransformation products are investigated here for the first time. Cunninghamella elegans CICC 40250 was shown to most efficiently hydroxylate 10-deoxoartemisinin, and could serve as a model organism for microbial transformation. This method could be used to generate additional hydroxylated 10-deoxoartemisinins for further research.

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“…Electron ionization (EI-MS) and high resolution electron ionization mass spectra (HREI-MS) were recorded on JEOL JMS600H mass spectrometer (JEOL, Japan). 1 H-, 13 C-and 2D-NMR spectra were recorded on Bruker Avance spectrometers (Bruker, Switzerland) in CD 3 OD. X-Ray diffraction data of the compound 6 was recorded on Bruker SMART APEX II single-crystal X-ray diffractometer (Germany).…”

Section: Methodsmentioning

confidence: 99%

“…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: 98%

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 danazol with Cunninghamella blakesleeana and anti-cancer activity of danazol and its transformed products

Cited by 12 publications

References 23 publications

A New Acetylcholinesterase Inhibitor from Green Glycosylation of Trachyloban-19-oic Acid by Mucor plumbeus

A New Acetylcholinesterase Inhibitor from Green Glycosylation of Trachyloban-19-oic Acid by Mucor plumbeus

Evaluation of Microbial Transformation of 10-deoxoartemisinin by UPLC-ESI-Q-TOF-MSE

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

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