Structure-activity relationship of atorvastatin derivatives for metabolic activation by hydrolases

1. We investigated the structure-activity relationship of 31 kinds of synthesized atorvastatin esters, thioesters, amides and lactone, selected as prodrug models, for metabolic activation by microsomes and hydrolases. 2. The susceptibility to human carboxylesterase 1 (hCES1) was influenced not only...

Full description

Saved in:
Bibliographic Details
Published inXenobiotica Vol. 50; no. 3; pp. 261 - 269
Main Authors Mizoi, Kenta, Takahashi, Masato, Sakai, Sachiko, Ogihara, Takuo, Haba, Masami, Hosokawa, Masakiyo
Format Journal Article
LanguageEnglish
Published England Taylor & Francis 03.03.2020
Subjects
Activation, Metabolic
atorvastatin
Atorvastatin - metabolism
Carboxylesterase
Carboxylic Ester Hydrolases
Hydrolases - metabolism
metabolic activation
Microsomes, Liver - metabolism
prodrug
Prodrugs
Structure-Activity Relationship
Substrate Specificity
prodrug
Carboxylesterase
atorvastatin
structure-activity relationship
metabolic activation
Online AccessGet full text

Cover

Abstract 1. We investigated the structure-activity relationship of 31 kinds of synthesized atorvastatin esters, thioesters, amides and lactone, selected as prodrug models, for metabolic activation by microsomes and hydrolases. 2. The susceptibility to human carboxylesterase 1 (hCES1) was influenced not only by the size of the acyl group and alkoxy group but also by the degree of steric crowding around the alkoxy group. 3. The susceptibility to human carboxylesterase 2 (hCES2) increased with a decrease in electron density around the alkoxy group of the substrate. 4. Lactone was specifically hydrolyzed by paraoxonase 3 (PON3). 5. These findings should be useful in prodrug design for controlling metabolic activation.
AbstractList 1. We investigated the structure-activity relationship of 31 kinds of synthesized atorvastatin esters, thioesters, amides and lactone, selected as prodrug models, for metabolic activation by microsomes and hydrolases.2. The susceptibility to human carboxylesterase 1 (hCES1) was influenced not only by the size of the acyl group and alkoxy group but also by the degree of steric crowding around the alkoxy group.3. The susceptibility to human carboxylesterase 2 (hCES2) increased with a decrease in electron density around the alkoxy group of the substrate.4. Lactone was specifically hydrolyzed by paraoxonase 3 (PON3).5. These findings should be useful in prodrug design for controlling metabolic activation.
1. We investigated the structure-activity relationship of 31 kinds of synthesized atorvastatin esters, thioesters, amides and lactone, selected as prodrug models, for metabolic activation by microsomes and hydrolases. 2. The susceptibility to human carboxylesterase 1 (hCES1) was influenced not only by the size of the acyl group and alkoxy group but also by the degree of steric crowding around the alkoxy group. 3. The susceptibility to human carboxylesterase 2 (hCES2) increased with a decrease in electron density around the alkoxy group of the substrate. 4. Lactone was specifically hydrolyzed by paraoxonase 3 (PON3). 5. These findings should be useful in prodrug design for controlling metabolic activation.
Author Takahashi, Masato
Hosokawa, Masakiyo
Ogihara, Takuo
Mizoi, Kenta
Sakai, Sachiko
Haba, Masami
Author_xml – sequence: 1
  givenname: Kenta
  surname: Mizoi
  fullname: Mizoi, Kenta
  organization: Faculty of Pharmacy, Takasaki University of Health and Welfare
– sequence: 2
  givenname: Masato
  surname: Takahashi
  fullname: Takahashi, Masato
  organization: Faculty of Pharmacy, Chiba Institute of Science
– sequence: 3
  givenname: Sachiko
  surname: Sakai
  fullname: Sakai, Sachiko
  organization: Faculty of Pharmacy, Chiba Institute of Science
– sequence: 4
  givenname: Takuo
  surname: Ogihara
  fullname: Ogihara, Takuo
  organization: Faculty of Pharmacy, Takasaki University of Health and Welfare
– sequence: 5
  givenname: Masami
  surname: Haba
  fullname: Haba, Masami
  organization: Faculty of Pharmacy, Chiba Institute of Science
– sequence: 6
  givenname: Masakiyo
  surname: Hosokawa
  fullname: Hosokawa, Masakiyo
  email: masakiyo@cis.ac.jp
  organization: Faculty of Pharmacy, Chiba Institute of Science
BackLink https://www.ncbi.nlm.nih.gov/pubmed/31173561$$D View this record in MEDLINE/PubMed
BookMark eNp9kE1P5DAMhiMEguHjJ4By5NLZfDSd9AZCu7AS0h4WzpGbuCKobYYkHdR_T4cZOHKyZT2vLT-n5HAIAxJyydmSM81-MVbWWqhyKRivl7wSiml5QBZcVlWhaqEPyWLLFFvohJym9MoYq7gQx-REcr6SquIL0vzPcbR5jFiAzX7j80QjdpB9GNKLX9PQUsghbiDleThQh9Fv5m6DibYh0h4zNKHzln7mP4O0mejL5GLoIGE6J0ctdAkv9vWMPP_5_XT3UDz-u_97d_tY2FKKXKgKhSydVsKu2gpQ8cahZqosQctWCuDKtUI30mkNNczPO4m1XTXCSl1jI8_I9W7vOoa3EVM2vU8Wuw4GDGMyQpSy1JLVfEbVDrUxpBSxNevoe4iT4cxs9ZovvWar1-z1zrmr_Ymx6dF9p758zsDNDvDDLKeH9xA7ZzJMXYhthMH6NMM_3vgAJeqN0Q
CitedBy_id crossref_primary_10_3390_molecules25245980
crossref_primary_10_1038_s41598_022_25802_1
crossref_primary_10_1080_00498254_2022_2119179
crossref_primary_10_1016_j_jhazmat_2020_125026
crossref_primary_10_1186_s43141_022_00443_z
crossref_primary_10_3390_biomedicines8100374
crossref_primary_10_1002_chir_23141
crossref_primary_10_3390_ph17010035
crossref_primary_10_1016_j_dmpk_2021_100391
crossref_primary_10_1016_j_ejps_2020_105455
Cites_doi 10.1124/dmd.109.026567
10.1016/j.bmcl.2018.02.035
10.1124/dmd.104.000554
10.1124/dmd.110.034454
10.1016/j.bcp.2016.07.007
10.1146/annurev.pharmtox.38.1.257
10.1124/dmd.113.051714
10.1023/A:1011625728803
10.1007/s00228-012-1315-5
10.1194/jlr.M400511-JLR200
10.1124/dmd.104.000620
10.1124/dmd.111.039628
10.1006/abbi.2001.2346
10.1124/dmd.111.038141
10.1124/jpet.106.110577
10.2133/dmpk.23.73
10.2133/dmpk.DMPK-12-RV-042
10.1016/j.bcp.2011.08.003
10.1248/bpb.20.869
10.1021/jo01097a026
10.1016/j.bmcl.2015.12.069
10.1124/jpet.104.067116
10.3390/molecules13020412
10.1124/dmd.107.015727
ContentType Journal Article
Copyright 2019 Informa UK Limited, trading as Taylor & Francis Group 2019
Copyright_xml – notice: 2019 Informa UK Limited, trading as Taylor & Francis Group 2019
DBID CGR
CUY
CVF
ECM
EIF
NPM
AAYXX
CITATION
7X8
DOI 10.1080/00498254.2019.1625083
DatabaseName Medline
MEDLINE
MEDLINE (Ovid)
MEDLINE
MEDLINE
PubMed
CrossRef
MEDLINE - Academic
DatabaseTitle MEDLINE
Medline Complete
MEDLINE with Full Text
PubMed
MEDLINE (Ovid)
CrossRef
MEDLINE - Academic
DatabaseTitleList MEDLINE
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
– sequence: 2
  dbid: EIF
  name: MEDLINE
  url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search
  sourceTypes: Index Database
DeliveryMethod fulltext_linktorsrc
Discipline Chemistry
Pharmacy, Therapeutics, & Pharmacology
EISSN 1366-5928
EndPage 269
ExternalDocumentID 10_1080_00498254_2019_1625083
31173561
1625083
Genre General Xenobiochemistry
Journal Article
GrantInformation_xml – fundername: JSPS KAKENHI
  grantid: 9; 8
GroupedDBID ---
00X
03L
0BK
0R~
123
29R
36B
4.4
5RE
AAJNR
AALUX
AAMIU
AAPUL
AAPXX
AAQRR
ABBKH
ABDBF
ABEIZ
ABLKL
ABPTK
ABUPF
ACENM
ACFUF
ACGEJ
ACGFS
ACLSK
ADCVX
ADFCX
ADRBQ
ADXPE
AECIN
AEGXH
AENEX
AEOZL
AEYQI
AFKVX
AFWLO
AGDLA
AGFJD
AGRBW
AGYJP
AIJEM
AIRBT
AJWEG
AKBVH
ALIIL
ALMA_UNASSIGNED_HOLDINGS
ALQZU
BABNJ
BLEHA
BOHLJ
CCCUG
CS3
DKSSO
DTRLO
DU5
EAP
EBC
EBD
EBS
EBX
EDH
EMB
EMK
EMOBN
EPL
ESX
F5P
H13
HZ~
J.N
KRBQP
KWAYT
KYCEM
L7B
LJTGL
M4Z
MK0
O9-
RNANH
RVRKI
SV3
TFDNU
TFL
TFW
TUS
UHWXJ
V1S
~1N
.GJ
53G
5VS
AACCU
AALIY
ABCRQ
ABJNI
ABLIJ
ABXYU
ACIEZ
AFAUU
AFQCT
AGAFX
AJEBJ
AJXHO
ALYBC
AWYRJ
BVLLS
CAG
CGR
COF
CUY
CVF
DEIEU
DLVIE
DZHFC
ECM
EIF
EJD
JFOCU
M44
NPM
NUSFT
OVD
QRXOQ
TBQAZ
TEORI
TERGH
TUROJ
ZGI
ZXP
~KM
AAYXX
CITATION
7X8
ID FETCH-LOGICAL-c432t-56e234d852c7f6ae51bde80544a83f32a15df28b3d88a9a982d3e9c7b2c389eb3
ISSN 0049-8254
IngestDate Fri Oct 25 05:19:49 EDT 2024
Fri Dec 06 04:52:19 EST 2024
Wed Oct 16 00:46:20 EDT 2024
Tue Jun 13 19:27:57 EDT 2023
IsPeerReviewed true
IsScholarly true
Issue 3
Keywords prodrug
Carboxylesterase
atorvastatin
structure-activity relationship
metabolic activation
Language English
LinkModel OpenURL
MergedId FETCHMERGED-LOGICAL-c432t-56e234d852c7f6ae51bde80544a83f32a15df28b3d88a9a982d3e9c7b2c389eb3
Notes ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
PMID 31173561
PQID 2243483091
PQPubID 23479
PageCount 9
ParticipantIDs proquest_miscellaneous_2243483091
pubmed_primary_31173561
crossref_primary_10_1080_00498254_2019_1625083
informaworld_taylorfrancis_310_1080_00498254_2019_1625083
PublicationCentury 2000
PublicationDate 2020-03-03
PublicationDateYYYYMMDD 2020-03-03
PublicationDate_xml – month: 03
  year: 2020
  text: 2020-03-03
  day: 03
PublicationDecade 2020
PublicationPlace England
PublicationPlace_xml – name: England
PublicationTitle Xenobiotica
PublicationTitleAlternate Xenobiotica
PublicationYear 2020
Publisher Taylor & Francis
Publisher_xml – name: Taylor & Francis
References CIT0010
CIT0011
Zhang QY (CIT0028) 1999; 27
CIT0013
CIT0016
CIT0018
Kuo CL (CIT0015) 1998; 26
CIT0017
CIT0019
CIT0021
CIT0020
CIT0001
CIT0023
CIT0022
Kamendulis LM (CIT0014) 1996; 279
CIT0003
CIT0025
CIT0002
CIT0024
CIT0005
CIT0027
CIT0004
CIT0026
CIT0007
CIT0006
CIT0009
CIT0008
Humerickhouse R (CIT0012) 2000; 60
References_xml – ident: CIT0027
  doi: 10.1124/dmd.109.026567
– ident: CIT0023
  doi: 10.1016/j.bmcl.2018.02.035
– ident: CIT0022
  doi: 10.1124/dmd.104.000554
– ident: CIT0004
  doi: 10.1124/dmd.110.034454
– ident: CIT0003
  doi: 10.1016/j.bcp.2016.07.007
– ident: CIT0019
  doi: 10.1146/annurev.pharmtox.38.1.257
– ident: CIT0007
  doi: 10.1124/dmd.113.051714
– ident: CIT0001
  doi: 10.1023/A:1011625728803
– ident: CIT0021
  doi: 10.1007/s00228-012-1315-5
– ident: CIT0002
  doi: 10.1194/jlr.M400511-JLR200
– ident: CIT0006
  doi: 10.1124/dmd.104.000620
– ident: CIT0026
  doi: 10.1124/dmd.111.039628
– ident: CIT0010
  doi: 10.1006/abbi.2001.2346
– volume: 60
  start-page: 1189
  year: 2000
  ident: CIT0012
  publication-title: Cancer Res
  contributor:
    fullname: Humerickhouse R
– ident: CIT0008
  doi: 10.1124/dmd.111.038141
– ident: CIT0025
  doi: 10.1124/jpet.106.110577
– volume: 27
  start-page: 804
  year: 1999
  ident: CIT0028
  publication-title: Drug Metab Dispos
  contributor:
    fullname: Zhang QY
– ident: CIT0009
  doi: 10.2133/dmpk.23.73
– volume: 26
  start-page: 653
  year: 1998
  ident: CIT0015
  publication-title: Drug Metab Dispos
  contributor:
    fullname: Kuo CL
– ident: CIT0005
  doi: 10.2133/dmpk.DMPK-12-RV-042
– ident: CIT0018
  doi: 10.1016/j.bcp.2011.08.003
– ident: CIT0024
  doi: 10.1248/bpb.20.869
– ident: CIT0016
  doi: 10.1021/jo01097a026
– ident: CIT0017
  doi: 10.1016/j.bmcl.2015.12.069
– ident: CIT0020
  doi: 10.1124/jpet.104.067116
– ident: CIT0011
  doi: 10.3390/molecules13020412
– volume: 279
  start-page: 713
  year: 1996
  ident: CIT0014
  publication-title: J Pharmacol Exp Ther
  contributor:
    fullname: Kamendulis LM
– ident: CIT0013
  doi: 10.1124/dmd.107.015727
SSID ssj0006122
Score 2.367382
Snippet 1. We investigated the structure-activity relationship of 31 kinds of synthesized atorvastatin esters, thioesters, amides and lactone, selected as prodrug...
SourceID proquest
crossref
pubmed
informaworld
SourceType Aggregation Database
Index Database
Publisher
StartPage 261
SubjectTerms Activation, Metabolic
atorvastatin
Atorvastatin - metabolism
Carboxylesterase
Carboxylic Ester Hydrolases
Hydrolases - metabolism
metabolic activation
Microsomes, Liver - metabolism
prodrug
Prodrugs
Structure-Activity Relationship
Substrate Specificity
Title Structure-activity relationship of atorvastatin derivatives for metabolic activation by hydrolases
URI https://www.tandfonline.com/doi/abs/10.1080/00498254.2019.1625083
https://www.ncbi.nlm.nih.gov/pubmed/31173561
https://search.proquest.com/docview/2243483091
Volume 50
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Za9wwEBbtBtq8hDa9Nj1QoeSl8WJbsi0_JmlDKGwb6Ab2zehyY5bYYddb2Pz6jiRfaRJ6vBgjYVn4-yzPyDPfIPQh8amArzr3Yporj7I48lKtpJcyRbSihEhu8p2nX-PTc_plHs37gEybXVKLiby-M6_kf1CFNsDVZMn-A7LdoNAA54AvHAFhOP4Vxt-t-Ot6qT2TnmCrQCzb4DYThGX-8YNP_ZObtCEb9rq0xcyM0qwJL7zUNXDAyFzb6x0XwB692KgluLyrJr6wsV3nujSaTfUgumdaXFdFk95Td60zvjCJYrZc8McpX8Ecuo0c6CrcTrS8KBZd-7cfhVGOtuzhi3U13IwAz9NEY7kFSrsFlMSxF6VNwnezwjpp2YZJZLhcOiH2W8t4G_dIU-PAmgC8dBKAp-a7ojcDaK8uLbYkCBISudF-089uux6iLSOWSEdo6_Do09FJ970GGy9sc7uM6vpdd91Gj9pxbhgwN-Rt73dSrLEye4J2Gi8DHzrKPEUPdLmLHh-3xf120f6ZkyzfHOBZn4G3OsD7-KwXM988Q-I2x_CQY7jK8ZBjeMAxDJPGHcdwzzEsNrjn2HN0fvJ5dnzqNXU5PElJWHtRrENCFYtCmeQx11EglGZg-1POSE5CHkQqD5kgijGecnia8N6nMhGhBPNYC_ICjcqq1K8QBvOJ-dKPfaEUjZQWTIF_HQWc5iyhUo7RpH3Y2ZWTX8mCTtXWAZUZoLIGqDFKh5Bktd33yl2Rmoz84dr3LX4ZwGH-nPFSV-tVBnYuoYyAbT1GLx2w3XRaXuzd2_Mabffvyhs0Atz0WzBla_Gu4eIv6Qyeww
link.rule.ids 314,780,784,27924,27925
linkProvider EBSCOhost
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=Structure-activity+relationship+of+atorvastatin+derivatives+for+metabolic+activation+by+hydrolases&rft.jtitle=Xenobiotica&rft.au=Mizoi%2C+Kenta&rft.au=Takahashi%2C+Masato&rft.au=Sakai%2C+Sachiko&rft.au=Ogihara%2C+Takuo&rft.date=2020-03-03&rft.eissn=1366-5928&rft.volume=50&rft.issue=3&rft.spage=261&rft_id=info:doi/10.1080%2F00498254.2019.1625083&rft_id=info%3Apmid%2F31173561&rft.externalDocID=31173561
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0049-8254&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0049-8254&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0049-8254&client=summon