Morphine-6-Glucuronide Isomers-Synthesis and Biological Evaluation

Jixia Yang; Guanyi Lu; Gongzheng Zhang; Xiaodi Wang; Hongliang Wen; Cipan Huang; Jiazhen Yin; Jin Li

doi:10.1002/bkcs.12112

Morphine-6-Glucuronide Isomers-Synthesis and Biological Evaluation

Jixia Yang, Guanyi Lu, Gongzheng Zhang, Xiaodi Wang, Hongliang Wen^*, Cipan Huang, Jiazhen Yin, Jin Li^*

^*Corresponding author for this work

School of Chemistry and Chemical Engineering

Research output: Contribution to journal › Article › peer-review

1 Citation (Scopus)

Abstract

Morphine-6β-D-glucuronide (M6βG), an active metabolite of morphine, and its isomer morphine-6α-D-glucuronide (M6αG) were synthesized from 3-O-protected morphinethrough glycosylation and alkaline hydrolysis. All structures were determined by spectroscopic analysis, and especially it is the first time to report the single crystal of compound M6αG. In vitro binding assay showed that M6βG bound to mu opioid receptor (MOR), kappa opioid receptor (KOR), and delta opioid receptor (DOR) with nanomolar affinity (K_i = 28.03, 116.88, and 375.13 nM) and M6αG bound to them with similar affinity (K_i = 1070.13, 20 637.93, and 677.36 nM). The selectivity of M6αG toward KOR is much higher. Hot-plate test showed that the analgesic effect of M6βG is better than that of M6αG, that is maybe because the mechanism of M6αG is different.

Original language	English
Pages (from-to)	1073-1079
Number of pages	7
Journal	Bulletin of the Korean Chemical Society
Volume	41
Issue number	11
DOIs	https://doi.org/10.1002/bkcs.12112
Publication status	Published - Nov 2020

Keywords

Binding assay
Hot-plate test; analgesic activity
Morphine-6α-D-glucuronide
Opioid receptor

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10.1002/bkcs.12112

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title = "Morphine-6-Glucuronide Isomers-Synthesis and Biological Evaluation",

abstract = "Morphine-6β-D-glucuronide (M6βG), an active metabolite of morphine, and its isomer morphine-6α-D-glucuronide (M6αG) were synthesized from 3-O-protected morphinethrough glycosylation and alkaline hydrolysis. All structures were determined by spectroscopic analysis, and especially it is the first time to report the single crystal of compound M6αG. In vitro binding assay showed that M6βG bound to mu opioid receptor (MOR), kappa opioid receptor (KOR), and delta opioid receptor (DOR) with nanomolar affinity (Ki = 28.03, 116.88, and 375.13 nM) and M6αG bound to them with similar affinity (Ki = 1070.13, 20 637.93, and 677.36 nM). The selectivity of M6αG toward KOR is much higher. Hot-plate test showed that the analgesic effect of M6βG is better than that of M6αG, that is maybe because the mechanism of M6αG is different.",

keywords = "Binding assay, Hot-plate test; analgesic activity, Morphine-6α-D-glucuronide, Opioid receptor",

author = "Jixia Yang and Guanyi Lu and Gongzheng Zhang and Xiaodi Wang and Hongliang Wen and Cipan Huang and Jiazhen Yin and Jin Li",

note = "Publisher Copyright: {\textcopyright} 2020 Korean Chemical Society, Seoul & Wiley-VCH GmbH",

year = "2020",

month = nov,

doi = "10.1002/bkcs.12112",

language = "English",

volume = "41",

pages = "1073--1079",

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T1 - Morphine-6-Glucuronide Isomers-Synthesis and Biological Evaluation

AU - Yang, Jixia

AU - Lu, Guanyi

AU - Zhang, Gongzheng

AU - Wang, Xiaodi

AU - Wen, Hongliang

AU - Huang, Cipan

AU - Yin, Jiazhen

AU - Li, Jin

PY - 2020/11

Y1 - 2020/11

N2 - Morphine-6β-D-glucuronide (M6βG), an active metabolite of morphine, and its isomer morphine-6α-D-glucuronide (M6αG) were synthesized from 3-O-protected morphinethrough glycosylation and alkaline hydrolysis. All structures were determined by spectroscopic analysis, and especially it is the first time to report the single crystal of compound M6αG. In vitro binding assay showed that M6βG bound to mu opioid receptor (MOR), kappa opioid receptor (KOR), and delta opioid receptor (DOR) with nanomolar affinity (Ki = 28.03, 116.88, and 375.13 nM) and M6αG bound to them with similar affinity (Ki = 1070.13, 20 637.93, and 677.36 nM). The selectivity of M6αG toward KOR is much higher. Hot-plate test showed that the analgesic effect of M6βG is better than that of M6αG, that is maybe because the mechanism of M6αG is different.

AB - Morphine-6β-D-glucuronide (M6βG), an active metabolite of morphine, and its isomer morphine-6α-D-glucuronide (M6αG) were synthesized from 3-O-protected morphinethrough glycosylation and alkaline hydrolysis. All structures were determined by spectroscopic analysis, and especially it is the first time to report the single crystal of compound M6αG. In vitro binding assay showed that M6βG bound to mu opioid receptor (MOR), kappa opioid receptor (KOR), and delta opioid receptor (DOR) with nanomolar affinity (Ki = 28.03, 116.88, and 375.13 nM) and M6αG bound to them with similar affinity (Ki = 1070.13, 20 637.93, and 677.36 nM). The selectivity of M6αG toward KOR is much higher. Hot-plate test showed that the analgesic effect of M6βG is better than that of M6αG, that is maybe because the mechanism of M6αG is different.

KW - Binding assay

KW - Hot-plate test; analgesic activity

KW - Morphine-6α-D-glucuronide

KW - Opioid receptor

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DO - 10.1002/bkcs.12112

M3 - Article

AN - SCOPUS:85093534937

SN - 0253-2964

VL - 41

SP - 1073

EP - 1079

JO - Bulletin of the Korean Chemical Society

JF - Bulletin of the Korean Chemical Society

IS - 11

ER -

Morphine-6-Glucuronide Isomers-Synthesis and Biological Evaluation

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