Abstract
Iminium quaternary protoberberine alkaloids (QPA) have been found to be novel P2X7 antagonists. To assess their structure-activity relationships, these compounds were modified at their R1 and R2 groups and assayed for their ability to inhibit the 2′(3′)-O-(4-benzoylbenzoyl)-ATP (BzATP)-induced uptake of fluorescent ethidium by HEK-293 cells stably expressing the human P2X7 receptor, and their ability to inhibit BzATP-induced IL-1β release by differentiated THP-1 cells. Compounds 15a and 15d, with alkyl groups at the R1 position, and especially compound 19h, with the 2-NO2-4,5-dimethoxy-benzyl group at the R2 position, had potent inhibitory efficacy as P2X7 antagonists.
| Original language | English |
|---|---|
| Pages (from-to) | 954-958 |
| Number of pages | 5 |
| Journal | Bioorganic and Medicinal Chemistry Letters |
| Volume | 19 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2009 Feb 1 |
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Keywords
- Antagonist
- Ethidium uptake
- Human P2X receptor
- IL-1β release
- Iminium quaternary protoberberine alkaloids
ASJC Scopus subject areas
- Pharmaceutical Science
- Drug Discovery
- Organic Chemistry
- Molecular Medicine
- Molecular Biology
- Clinical Biochemistry
- Biochemistry
Cite this
Synthesis and structure-activity relationships of novel, substituted 5,6-dihydrodibenzo[a,g]quinolizinium P2X7 antagonists. / Lee, Ga Eun; Lee, Ho Sung; Lee, So Deok; Kim, Jung Ho; Kim, Won-Ki; Kim, Yong Chul.
In: Bioorganic and Medicinal Chemistry Letters, Vol. 19, No. 3, 01.02.2009, p. 954-958.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Synthesis and structure-activity relationships of novel, substituted 5,6-dihydrodibenzo[a,g]quinolizinium P2X7 antagonists
AU - Lee, Ga Eun
AU - Lee, Ho Sung
AU - Lee, So Deok
AU - Kim, Jung Ho
AU - Kim, Won-Ki
AU - Kim, Yong Chul
PY - 2009/2/1
Y1 - 2009/2/1
N2 - Iminium quaternary protoberberine alkaloids (QPA) have been found to be novel P2X7 antagonists. To assess their structure-activity relationships, these compounds were modified at their R1 and R2 groups and assayed for their ability to inhibit the 2′(3′)-O-(4-benzoylbenzoyl)-ATP (BzATP)-induced uptake of fluorescent ethidium by HEK-293 cells stably expressing the human P2X7 receptor, and their ability to inhibit BzATP-induced IL-1β release by differentiated THP-1 cells. Compounds 15a and 15d, with alkyl groups at the R1 position, and especially compound 19h, with the 2-NO2-4,5-dimethoxy-benzyl group at the R2 position, had potent inhibitory efficacy as P2X7 antagonists.
AB - Iminium quaternary protoberberine alkaloids (QPA) have been found to be novel P2X7 antagonists. To assess their structure-activity relationships, these compounds were modified at their R1 and R2 groups and assayed for their ability to inhibit the 2′(3′)-O-(4-benzoylbenzoyl)-ATP (BzATP)-induced uptake of fluorescent ethidium by HEK-293 cells stably expressing the human P2X7 receptor, and their ability to inhibit BzATP-induced IL-1β release by differentiated THP-1 cells. Compounds 15a and 15d, with alkyl groups at the R1 position, and especially compound 19h, with the 2-NO2-4,5-dimethoxy-benzyl group at the R2 position, had potent inhibitory efficacy as P2X7 antagonists.
KW - Antagonist
KW - Ethidium uptake
KW - Human P2X receptor
KW - IL-1β release
KW - Iminium quaternary protoberberine alkaloids
UR - http://www.scopus.com/inward/record.url?scp=58549113754&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=58549113754&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2008.11.088
DO - 10.1016/j.bmcl.2008.11.088
M3 - Article
C2 - 19110420
AN - SCOPUS:58549113754
VL - 19
SP - 954
EP - 958
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
IS - 3
ER -