α-Ketoheterocycles Able to Inhibit the Generation of Prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) in Rat Mesangial Cells
Prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) is a key mediator of inflammation, and consequently huge efforts have been devoted to the development of novel agents able to regulate its formation. In this work, we present the synthesis of various α-ketoheterocycles and a study...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-02-01
|
| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/11/2/275 |
| _version_ | 1797396645896257536 |
|---|---|
| author | Anastasia Psarra Maria A. Theodoropoulou Martin Erhardt Marina Mertiri Christiana Mantzourani Sofia Vasilakaki Victoria Magrioti Andrea Huwiler George Kokotos |
| author_facet | Anastasia Psarra Maria A. Theodoropoulou Martin Erhardt Marina Mertiri Christiana Mantzourani Sofia Vasilakaki Victoria Magrioti Andrea Huwiler George Kokotos |
| author_sort | Anastasia Psarra |
| collection | DOAJ |
| description | Prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) is a key mediator of inflammation, and consequently huge efforts have been devoted to the development of novel agents able to regulate its formation. In this work, we present the synthesis of various α-ketoheterocycles and a study of their ability to inhibit the formation of PGE<sub>2</sub> at a cellular level. A series of α-ketobenzothiazoles, α-ketobenzoxazoles, α-ketobenzimidazoles, and α-keto-1,2,4-oxadiazoles were synthesized and chemically characterized. Evaluation of their ability to suppress the generation of PGE<sub>2</sub> in interleukin-1β plus forskolin-stimulated mesangial cells led to the identification of one α-ketobenzothiazole (GK181) and one α-ketobenzoxazole (GK491), which are able to suppress the PGE<sub>2</sub> generation at a nanomolar level. |
| first_indexed | 2024-03-09T00:54:23Z |
| format | Article |
| id | doaj.art-5030b9c8ecc3449b948d3c85a4284efe |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-09T00:54:23Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-5030b9c8ecc3449b948d3c85a4284efe2023-12-11T16:57:44ZengMDPI AGBiomolecules2218-273X2021-02-0111227510.3390/biom11020275α-Ketoheterocycles Able to Inhibit the Generation of Prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) in Rat Mesangial CellsAnastasia Psarra0Maria A. Theodoropoulou1Martin Erhardt2Marina Mertiri3Christiana Mantzourani4Sofia Vasilakaki5Victoria Magrioti6Andrea Huwiler7George Kokotos8Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, 15771 Athens, GreeceDepartment of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, 15771 Athens, GreeceInstitute of Pharmacology, University of Bern, CH-3010 Bern, SwitzerlandDepartment of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, 15771 Athens, GreeceDepartment of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, 15771 Athens, GreeceDepartment of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, 15771 Athens, GreeceDepartment of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, 15771 Athens, GreeceInstitute of Pharmacology, University of Bern, CH-3010 Bern, SwitzerlandDepartment of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, 15771 Athens, GreeceProstaglandin E<sub>2</sub> (PGE<sub>2</sub>) is a key mediator of inflammation, and consequently huge efforts have been devoted to the development of novel agents able to regulate its formation. In this work, we present the synthesis of various α-ketoheterocycles and a study of their ability to inhibit the formation of PGE<sub>2</sub> at a cellular level. A series of α-ketobenzothiazoles, α-ketobenzoxazoles, α-ketobenzimidazoles, and α-keto-1,2,4-oxadiazoles were synthesized and chemically characterized. Evaluation of their ability to suppress the generation of PGE<sub>2</sub> in interleukin-1β plus forskolin-stimulated mesangial cells led to the identification of one α-ketobenzothiazole (GK181) and one α-ketobenzoxazole (GK491), which are able to suppress the PGE<sub>2</sub> generation at a nanomolar level.https://www.mdpi.com/2218-273X/11/2/275anti-inflammatoryinhibitionα-ketobenzothiazolesmesangial cellsprostaglandin E<sub>2</sub> |
| spellingShingle | Anastasia Psarra Maria A. Theodoropoulou Martin Erhardt Marina Mertiri Christiana Mantzourani Sofia Vasilakaki Victoria Magrioti Andrea Huwiler George Kokotos α-Ketoheterocycles Able to Inhibit the Generation of Prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) in Rat Mesangial Cells Biomolecules anti-inflammatory inhibition α-ketobenzothiazoles mesangial cells prostaglandin E<sub>2</sub> |
| title | α-Ketoheterocycles Able to Inhibit the Generation of Prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) in Rat Mesangial Cells |
| title_full | α-Ketoheterocycles Able to Inhibit the Generation of Prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) in Rat Mesangial Cells |
| title_fullStr | α-Ketoheterocycles Able to Inhibit the Generation of Prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) in Rat Mesangial Cells |
| title_full_unstemmed | α-Ketoheterocycles Able to Inhibit the Generation of Prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) in Rat Mesangial Cells |
| title_short | α-Ketoheterocycles Able to Inhibit the Generation of Prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) in Rat Mesangial Cells |
| title_sort | α ketoheterocycles able to inhibit the generation of prostaglandin e sub 2 sub pge sub 2 sub in rat mesangial cells |
| topic | anti-inflammatory inhibition α-ketobenzothiazoles mesangial cells prostaglandin E<sub>2</sub> |
| url | https://www.mdpi.com/2218-273X/11/2/275 |
| work_keys_str_mv | AT anastasiapsarra aketoheterocyclesabletoinhibitthegenerationofprostaglandinesub2subpgesub2subinratmesangialcells AT mariaatheodoropoulou aketoheterocyclesabletoinhibitthegenerationofprostaglandinesub2subpgesub2subinratmesangialcells AT martinerhardt aketoheterocyclesabletoinhibitthegenerationofprostaglandinesub2subpgesub2subinratmesangialcells AT marinamertiri aketoheterocyclesabletoinhibitthegenerationofprostaglandinesub2subpgesub2subinratmesangialcells AT christianamantzourani aketoheterocyclesabletoinhibitthegenerationofprostaglandinesub2subpgesub2subinratmesangialcells AT sofiavasilakaki aketoheterocyclesabletoinhibitthegenerationofprostaglandinesub2subpgesub2subinratmesangialcells AT victoriamagrioti aketoheterocyclesabletoinhibitthegenerationofprostaglandinesub2subpgesub2subinratmesangialcells AT andreahuwiler aketoheterocyclesabletoinhibitthegenerationofprostaglandinesub2subpgesub2subinratmesangialcells AT georgekokotos aketoheterocyclesabletoinhibitthegenerationofprostaglandinesub2subpgesub2subinratmesangialcells |