Oxidation and Degradation Products of Papaverine. Part I: Gadamer and Schulemann's Papaverinol Synthesis Revisited

“…Peaks at m / z 354, 340, 325 and 309 corresponded to (M-H) + , (M-CH 3 ) + , (M-OCH 3 ) + and (M-OCH 3 -CH 3 ) + fragments, respectively. Based on these data, metabolite 5 was elucidated as papaverine 3-ol [ 22 ] ( Figure 1 ).…”

Section: Resultsmentioning

confidence: 99%

Papaverinol-N-Oxide: A Microbial Biotransformation Product of Papaverine with Potential Antidiabetic and Antiobesity Activity Unveiled with In Silico Screening

et al. 2023

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Bioconversion of biosynthetic heterocyclic compounds has been utilized to produce new semisynthetic pharmaceuticals and study the metabolites of bioactive drugs used systemically. In this investigation, the biotransformation of natural heterocyclic alkaloid papaverine via filamentous fungi was explored. Molecular docking simulations, using protein tyrosine phosphatase 1B (PTP1B), α-glucosidase and pancreatic lipase (PL) as target enzymes, were performed to investigate the antidiabetic potential of papaverine and its metabolites in silico. The metabolites were isolated from biotransformation of papaverine with Cunninghamella elegans NRRL 2310, Rhodotorula rubra NRRL y1592, Penicillium chrysogeneum ATCC 10002 and Cunninghamella blackesleeana NRRL 1369 via reduction, demethylation, N-oxidation, oxidation and hydroxylation reactions. Seven metabolites were isolated: namely, 3,4-dihydropapaverine (metabolite 1), papaveroline (metabolite 2), 7-demethyl papaverine (metabolite 3), 6,4′-didemethyl papaverine (metabolite 4), papaverine-3-ol (metabolite 5), papaverinol (metabolite 6) and papaverinol N-oxide (metabolite 7). The structural elucidation of the metabolites was investigated with 1D and 2D NMR and mass spectroscopy (EI and ESI). The molecular docking studies showed that metabolite 7 exhibited better binding interactions with the target enzymes PTP1B, α-glucosidase and PL than did papaverine. Furthermore, papaverinol-N-oxide (7) also displayed inhibition of α-glucosidase and lipase enzymes comparable to that of their ligands (acarbose and orlistat, respectively), as unveiled with an in silico ADMET profile, molecular docking and molecular dynamics studies. In conclusion, this study provides evidence for enhanced inhibition of PTP1B, α-glucosidase and PL via some papaverine fungal transformation products and, therefore, potentially better antidiabetic and antiobesity effects than those of papaverine and other known therapeutic agents.

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“…The minor product of the preparation of papaverinol 50b from papaverine 50a, which has a violet fluorescence, has been identified as the 6a,12a-diazabenzo[a,g]fluorenylium salt 54 from its mass spectrum, but its mode of formation was not investigated. 47 Oxidation of O-methylarmepavine 55a and of laudanosine 55b with iodosylbenzene and tetrabutylammonium iodide has given the lactam 56, together with anisaldehyde 57a and veratric aldehyde 57b respectively. 28 Reaction of dihydropapaverine 58 with the bromoketones 59a-59d has given the pyrroles 60a-60d.…”

Section: Benzylisoquinolinesmentioning

confidence: 99%

β-Phenylethylamines and the isoquinoline alkaloids

Bentley

2004

Nat. Prod. Rep.

124

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This review covers beta-phenylethylamines and isoquinoline alkaloids derived from them, including further products of oxidation. condensation with formaldehyde and rearrangement, some of which do not contain an isoquinoline system, together with naphthylisoquinoline alkaloids, which have a different biogenetic origin. The occurrence of the alkaloids, with the structures of new bases, together with their reactions, syntheses and biological activities are reported. The literature from July 2002 to June 2003 is reviewed, with 568 references cited.

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Oxidation and Degradation Products of Papaverine. Part I: Gadamer and Schulemann's Papaverinol Synthesis Revisited

Cited by 11 publications

References 4 publications

Spectroscopic study and G-quadruplex DNA binding affinity of two bioactive papaverine-derived ligands

Spectroscopic study and G-quadruplex DNA binding affinity of two bioactive papaverine-derived ligands

Papaverinol-N-Oxide: A Microbial Biotransformation Product of Papaverine with Potential Antidiabetic and Antiobesity Activity Unveiled with In Silico Screening

β-Phenylethylamines and the isoquinoline alkaloids

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