Computational Analysis of Dipyrone Metabolite 4-Aminoantipyrine as a Cannabinoid Receptor 1 Agonist
Cannabinoid receptor 1 has its crystallographic structure available in complex with agonists and inverse agonists, which paved the way to establish an understanding of the structural basis of interactions with ligands. Dipyrone is a prodrug with analgesic capabilities and which is widely used in som...
Saved in:
Published in | Current medicinal chemistry |
---|---|
Main Authors | , |
Format | Journal Article |
Language | English |
Published |
United Arab Emirates
01.01.2020
|
Subjects | |
Online Access | Get more information |
Cover
Loading…
Abstract | Cannabinoid receptor 1 has its crystallographic structure available in complex with agonists and inverse agonists, which paved the way to establish an understanding of the structural basis of interactions with ligands. Dipyrone is a prodrug with analgesic capabilities and which is widely used in some countries. Recently it was shown some evidence of a dipyrone metabolite acting over the Cannabinoid Receptor 1.
Our goal here is to explore the dipyrone metabolite 4-aminoantipyrine as a Cannabinoid Receptor 1 agonist, reviewing dipyrone characteristics, and investigating the structural basis for its interaction with Cannabinoid Receptor 1.
We reviewed here recent functional studies related to the dipyrone metabolite focusing on its action as a Cannabinoid Receptor 1 agonist. We also analyzed protein-ligand interactions for this complex obtained through docking simulations against the crystallographic structure of the Cannabinoid Receptor 1.
Analysis of the crystallographic structure and docking simulations revealed that most of the interactions present in the docked pose were also present in the crystallographic structure of Cannabinoid Receptor 1 and agonist.
Analysis of the complex of 4-aminoantipyrine and Cannabinoid Receptor 1 revealed the pivotal role played by residues Phe 170, Phe 174, Phe 177, Phe 189, Leu 193, Val 196, and Phe 379, besides the conserved hydrogen bond at Ser 383. The mechanistic analysis and the present computational study suggest that the dipyrone metabolite 4-aminoantipyrine interacts with Cannabinoid Receptor 1. |
---|---|
AbstractList | Cannabinoid receptor 1 has its crystallographic structure available in complex with agonists and inverse agonists, which paved the way to establish an understanding of the structural basis of interactions with ligands. Dipyrone is a prodrug with analgesic capabilities and which is widely used in some countries. Recently it was shown some evidence of a dipyrone metabolite acting over the Cannabinoid Receptor 1.
Our goal here is to explore the dipyrone metabolite 4-aminoantipyrine as a Cannabinoid Receptor 1 agonist, reviewing dipyrone characteristics, and investigating the structural basis for its interaction with Cannabinoid Receptor 1.
We reviewed here recent functional studies related to the dipyrone metabolite focusing on its action as a Cannabinoid Receptor 1 agonist. We also analyzed protein-ligand interactions for this complex obtained through docking simulations against the crystallographic structure of the Cannabinoid Receptor 1.
Analysis of the crystallographic structure and docking simulations revealed that most of the interactions present in the docked pose were also present in the crystallographic structure of Cannabinoid Receptor 1 and agonist.
Analysis of the complex of 4-aminoantipyrine and Cannabinoid Receptor 1 revealed the pivotal role played by residues Phe 170, Phe 174, Phe 177, Phe 189, Leu 193, Val 196, and Phe 379, besides the conserved hydrogen bond at Ser 383. The mechanistic analysis and the present computational study suggest that the dipyrone metabolite 4-aminoantipyrine interacts with Cannabinoid Receptor 1. |
Author | de Azevedo, Jr, Walter Filgueira Russo, Silvana |
Author_xml | – sequence: 1 givenname: Silvana surname: Russo fullname: Russo, Silvana organization: Laboratory of Computational Systems Biology, School of Sciences - Pontifical Catholic University of Rio Grande do Sul (PUCRS), Av. Ipiranga, 6681, Porto Alegre-RS 90619-900. Brazil – sequence: 2 givenname: Walter Filgueira surname: de Azevedo, Jr fullname: de Azevedo, Jr, Walter Filgueira organization: Laboratory of Computational Systems Biology, School of Sciences - Pontifical Catholic University of Rio Grande do Sul (PUCRS), Av. Ipiranga, 6681, Porto Alegre-RS 90619-900. Brazil |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/31490743$$D View this record in MEDLINE/PubMed |
BookMark | eNo1j91KxDAQhYMo7o--gsQHqOanSZrLUl0VVgRR8G5JmkQibVKa7EXf3oh6Luac4YMZzgachhgsANcY3RAs6lskiWy4oIQXYYkk4pgxSuUJWONGsKrkjxXYpPSFECYSoXOworiWSNR0DfoujtMxq-xjUANsy1iSTzA6eOenZS7P4LPNSsfBZwvrqh19iCrkH-gLVAkq2KkQlC7AG_hqezvlOEMM288YfMoX4MypIdnLP9-C9939W_dY7V8enrp2X-lakFxRypx2lhmsiZKWc8SYLhsnDDecOmSItY0kqullX8pKIySnFDfG9tSJmmzB1e_d6ahHaw7T7Ec1L4f_tuQbWcRZPg |
CitedBy_id | crossref_primary_10_2174_0929867328666210623143526 crossref_primary_10_2174_0929867328666210806105810 crossref_primary_10_2174_0929867327666200515101820 crossref_primary_10_1007_s00044_020_02667_5 |
ContentType | Journal Article |
Copyright | Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net. |
Copyright_xml | – notice: Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net. |
DBID | NPM |
DOI | 10.2174/0929867326666190906155339 |
DatabaseName | PubMed |
DatabaseTitle | PubMed |
DatabaseTitleList | PubMed |
Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database |
DeliveryMethod | no_fulltext_linktorsrc |
Discipline | Medicine Chemistry Pharmacy, Therapeutics, & Pharmacology |
EISSN | 1875-533X |
ExternalDocumentID | 31490743 |
Genre | Journal Article |
GroupedDBID | --- .5. 0R~ 29F 36B 4.4 5GY AAEGP AAVXF ABEEF ABJNI ABVDF ACGFS ACGOD ACITR ACIWK ACPRK AENEX AFRAH AFUQM AGJNZ AHMBA ALIPV ALMA_UNASSIGNED_HOLDINGS ANTIV CS3 DU5 EBS F5P GH2 HZ~ IPNFZ KCGFV KFI NPM O9- P2P RIG |
ID | FETCH-LOGICAL-b472t-335fbfe5d1b2a9e66055b5d16251863f0d2ee892a8c9c6669d7963318dec3f742 |
IngestDate | Sat Sep 28 08:40:17 EDT 2024 |
IsPeerReviewed | true |
IsScholarly | true |
Keywords | docking dipyrone cannabinoid receptor 1 4-aminoantipyrine metamizole molecular interactions |
Language | English |
License | Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net. |
LinkModel | OpenURL |
MergedId | FETCHMERGED-LOGICAL-b472t-335fbfe5d1b2a9e66055b5d16251863f0d2ee892a8c9c6669d7963318dec3f742 |
PMID | 31490743 |
ParticipantIDs | pubmed_primary_31490743 |
PublicationCentury | 2000 |
PublicationDate | 2020-01-01 |
PublicationDateYYYYMMDD | 2020-01-01 |
PublicationDate_xml | – month: 01 year: 2020 text: 2020-01-01 day: 01 |
PublicationDecade | 2020 |
PublicationPlace | United Arab Emirates |
PublicationPlace_xml | – name: United Arab Emirates |
PublicationTitle | Current medicinal chemistry |
PublicationTitleAlternate | Curr Med Chem |
PublicationYear | 2020 |
SSID | ssj0012900 |
Score | 2.3874717 |
SecondaryResourceType | review_article |
Snippet | Cannabinoid receptor 1 has its crystallographic structure available in complex with agonists and inverse agonists, which paved the way to establish an... |
SourceID | pubmed |
SourceType | Index Database |
Title | Computational Analysis of Dipyrone Metabolite 4-Aminoantipyrine as a Cannabinoid Receptor 1 Agonist |
URI | https://www.ncbi.nlm.nih.gov/pubmed/31490743 |
hasFullText | |
inHoldings | 1 |
isFullTextHit | |
isPrint | |
link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3da9swEBfrBllfSpd9teuGBqMvrjdb_pIeQ7ZSBil9SFneir5cDK0dknSQ_vU9yVLsdS37yIOJJWyUu1_k39357hD6xEqZKi1kyJmMQpO6GFJFdZizglEeZ1TZ6PnkND85T7_PslnXs9Vml6zEZ3n7YF7J_2gVxkCvJkv2HzS7uSkMwHfQLxxBw3D8Kx23LRm8O69fX-RrNV8vGiCQE70CNZtE4yANR9dV3YAozaRhl3wZ8GDM65qDfdxUJlPRvOXSLII4GF02tcsN2lQycLWcXDzeVBbx7eI2cZsb-MnWo1pdmXbNflzpYHSrf2rVBnosTH7YSH1wXF1d3uhqwfsOCBL1HBC63TTB5gmBNs4e2pKNyWMjRITRvACyCB8gIcxQKbiG9a8B6c6vra4SMNwMufnz7L1q2X5qC20V1Ox4p8Z746JKhEXRAH10q_ry6Jq20cDf5561YVnHdBftOHMBj1rdv0BPdD1Ez8de7EM0mLiXI4bo8KwtQ74-wtMuq255hA_xWVegfP0SyV9wgz1ucFNijxvc4Qb_hhvMl5jjHm6wxw2OscPNK3R-_G06Pglds41QpAVZhUmSlaLUmYoF4UznYOZmAs7APo5pnpSRIlpTRjiVTIK8mCpg74YngtIyKYuUvEZPa1jfW4RzReGpyYAoA3dMgUNyJqSknMioELLQe-hNK9OLeVtR5cJLe__RmXdou8PeAXpWwl9Yvwc-uBIfrJLvAJnDXnU |
link.rule.ids | 786 |
linkProvider | National Library of Medicine |
openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Computational+Analysis+of+Dipyrone+Metabolite+4-Aminoantipyrine+as+a+Cannabinoid+Receptor+1+Agonist&rft.jtitle=Current+medicinal+chemistry&rft.au=Russo%2C+Silvana&rft.au=de+Azevedo%2C+Jr%2C+Walter+Filgueira&rft.date=2020-01-01&rft.eissn=1875-533X&rft_id=info:doi/10.2174%2F0929867326666190906155339&rft_id=info%3Apmid%2F31490743&rft_id=info%3Apmid%2F31490743&rft.externalDocID=31490743 |