Biotransformation of papaverine and in silico docking studies of the metabolites on human phosphodiesterase 10a

Eliwa, Duaa; Albadry, Mohamed A.; Ibrahim, Abdel-Rahim S.; Kabbash, Amal; Meepagala, Kumudini M.; Khan, Ikhlas A.; El‐Aasr, Mona; Ross, Samir A.

doi:10.1016/j.phytochem.2020.112598

Cited by 11 publications

(9 citation statements)

References 14 publications

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“…As such, the development of PDE10A inhibitors has drawn continuous attention, with a number of preclinical and clinical studies recently reported 16 , 17 , 18 , 19 , 20 . Of note, the plant-derived PDE10A inhibitor, papaverine, was the first compounds that entered the clinical arena 21 , 22 . Nonetheless, the use of papaverine was hampered by the relatively low potency and selectivity, as well as the relatively fast in vivo clearance.…”

Section: Introductionmentioning

confidence: 99%

Discovery of a highly specific 18F-labeled PET ligand for phosphodiesterase 10A enabled by novel spirocyclic iodonium ylide radiofluorination

Xiao

Wei

et al. 2022

Acta Pharmaceutica Sinica B

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Section: Introductionmentioning

confidence: 99%

Discovery of a highly specific 18F-labeled PET ligand for phosphodiesterase 10A enabled by novel spirocyclic iodonium ylide radiofluorination

Xiao

Wei

et al. 2022

Acta Pharmaceutica Sinica B

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“…Initial screening procedure was conducted as previously reported Eliwa et al [ 34 ]. In this case, 50 microbial cultures, obtained from the American Type Culture collection (ATCC, Rockville, Maryland), Northern Regional Research Laboratories (NRRL, Peoria, IL, USA.…”

Section: Methodsmentioning

confidence: 99%

Biotransformation of Modified Benzylisoquinoline Alkaloids: Boldine and Berberine and In Silico Molecular Docking Studies of Metabolites on Telomerase and Human Protein Tyrosine Phosphatase 1B

et al. 2022

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Natural nitrogen heterocycles biotransformation has been extensively used to prepare synthetic drugs and explore the fate of therapeutic agents inside the body. Herein, the ability of filamentous fungi to biotransform boldine and berberine was investigated. Docking simulation studies of boldine, berberine and their metabolites on the target enzymes: telomerase (TERT) and human protein tyrosine phosphatase 1B (PTP-1B) were also performed to investigate the anticancer and antidiabetic potentials of compounds in silico. The biotransformation of boldine and berberine with Cunninghamella elegans NRRL 2310, Rhodotorula rubra NRRL y1592, Penicillium chrysogeneum ATCC 10002, Cunninghamella blackesleeana MR198 and Cunninghamella blackesleeana NRRL 1369 via demethylation, N- oxidation, glucosidation, oxidation and hydroxylation reactions produced seven metabolites, namely: 1,10-didesmethyl-boldine (1), laurolitsine (2), 1,10-didesmethyl-norboldine (3), boldine-9-O-β-D-glucoside (4), tridesmethyl berberine (5), demethylene berberine (6), and lambertine (7). Primarily, the structures of the metabolites were established by one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) analyses and mass spectrometry. In silico molecular docking simulation of the metabolites of boldine and berberine to the proteins TERT and PTP-1B, respectively, revealed good binding MolDock scores comparable to boldine and berberine and favorable interactions with the catalytic sites of the proteins. In conclusion, this study presented promising biologically prepared nitrogen scaffolds (isoquinolines) of boldine and berberine.

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“…The data was in agreement with the literature. [94,102,147] papaverinol (17, C 20 H 21 NO 5 , white solid, 1 mg, 1 %): 1 H NMR (300 MHz, CDCl 3 ): δ = 8.42 (1H, d, J = 5.7 Hz, 3-H), 7.56 (1H, d, J = 5.7 Hz, 4-H), 7.16 (1H, s, 8-H), 7.09 (1H, s, 5-H), 6.93 (1H, dd, J = 8.1, 1.8 Hz, 6'-H), 6.86 (1H, d, J = 1.8 Hz, 2'-H), 6.79 (1H, d, J = 8.1 Hz, 5'-H), 6.20 (1H, s, 10-H), 4.00 (3H, s), 3.83 (3H, s), 3.82 (3H, s), 3.77 (3H, s). The data was in agreement with the literature.…”

Section: (+)-(4r5s7r11s)-mentioning

confidence: 99%

“…The data was in agreement with the literature. [147] strychnine (5, C 21 H), 1.41 (1H, ddd, J = 10.0, 3.7, 3.4 Hz, 13-H). Due to steric hindrance, the β,βconformation of the epoxide is unlikely to happen [117] concluding the product to be (R,R)-21α,22α-epoxystrychnine with an α,αconformation.…”

Section: (+)-(4r5s7r11s)-mentioning

confidence: 99%

Natural Product Diversification by One‐Step Biocatalysis using Human P450 3A4

et al. 2021

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Efficient synthetic techniques for the diversification of natural products are incremental for drug discovery processes of the pharmaceutical industry because these complex bioactive compounds often require an adjustment of properties. Human liver P450 3A4, key player of the body's detoxification system and decisive factor of a drug's metabolic fate, is renowned for its broad substrate scope including many natural products. In this study, we investigated the synthetic potential of human P450 3A4 for the diversification of natural product classes and isolated the produced metabolites of six selected natural products at a preparative 100-mg scale. Aided by efficient expression levels in P. pastoris, this whole-cell biocatalyst was found to be highly effective at the intended job allowing the identification of a total of 31 authentic human metabolites, many of them for the first time. By revealing an unprecedented degree of diversification, this study extends the synthetic repertoire for efficient enzymatic natural product modification in a one-step fashion and adds a completely new view to an old enzyme traditionally used for inhibition and toxicology studies.

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Biotransformation of papaverine and in silico docking studies of the metabolites on human phosphodiesterase 10a

Cited by 11 publications

References 14 publications

Discovery of a highly specific 18F-labeled PET ligand for phosphodiesterase 10A enabled by novel spirocyclic iodonium ylide radiofluorination

Discovery of a highly specific 18F-labeled PET ligand for phosphodiesterase 10A enabled by novel spirocyclic iodonium ylide radiofluorination

Biotransformation of Modified Benzylisoquinoline Alkaloids: Boldine and Berberine and In Silico Molecular Docking Studies of Metabolites on Telomerase and Human Protein Tyrosine Phosphatase 1B

Natural Product Diversification by One‐Step Biocatalysis using Human P450 3A4

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