Tetrahydroimidazo[4,5-<i>c</i>]pyridine-Based Inhibitors of <i>Porphyromonas gingivalis</i> Glutaminyl Cyclase
Periodontitis is a severe yet underestimated oral disease. Since it is linked to several systemic diseases, such as diabetes, artheriosclerosis, and even Alzheimer’s disease, growing interest in treating periodontitis has emerged recently. The major cause of periodontitis is a shift in the oral micr...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-11-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/14/12/1206 |
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| author | Daniel Ramsbeck Nadine Taudte Nadine Jänckel Stefanie Strich Jens-Ulrich Rahfeld Mirko Buchholz |
| author_facet | Daniel Ramsbeck Nadine Taudte Nadine Jänckel Stefanie Strich Jens-Ulrich Rahfeld Mirko Buchholz |
| author_sort | Daniel Ramsbeck |
| collection | DOAJ |
| description | Periodontitis is a severe yet underestimated oral disease. Since it is linked to several systemic diseases, such as diabetes, artheriosclerosis, and even Alzheimer’s disease, growing interest in treating periodontitis has emerged recently. The major cause of periodontitis is a shift in the oral microbiome. A keystone pathogen that is associated with this shift is <i>Porphyromonas gingivalis</i>. Hence, targeting <i>P. gingivalis</i> came into focus of drug discovery for the development of novel antiinfective compounds. Among others, glutaminyl cyclases (QCs) of oral pathogens might be promising drug targets. Here, we report the discovery and structure–activity relationship of a novel class of <i>P. gingivalis</i> QC inhibitors according to a tetrahydroimidazo[4,5-<i>c</i>]pyridine scaffold. Some compounds exhibited activity in the lower nanomolar range and thus were further characterized with regard to their selectivity and toxicity. |
| first_indexed | 2024-03-10T03:21:50Z |
| format | Article |
| id | doaj.art-c83c92b5888541eb8c2136912ad25b5a |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T03:21:50Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-c83c92b5888541eb8c2136912ad25b5a2023-11-23T10:02:27ZengMDPI AGPharmaceuticals1424-82472021-11-011412120610.3390/ph14121206Tetrahydroimidazo[4,5-<i>c</i>]pyridine-Based Inhibitors of <i>Porphyromonas gingivalis</i> Glutaminyl CyclaseDaniel Ramsbeck0Nadine Taudte1Nadine Jänckel2Stefanie Strich3Jens-Ulrich Rahfeld4Mirko Buchholz5Fraunhofer Institute for Cell Therapy and Immunology IZI, Department of Drug Design and Target Validation MWT, Weinbergweg 22, 06120 Halle (Saale), GermanyPerioTrap Pharmaceuticals GmbH, Weinbergweg 22, 06120 Halle (Saale), GermanyPerioTrap Pharmaceuticals GmbH, Weinbergweg 22, 06120 Halle (Saale), GermanyFraunhofer Institute for Cell Therapy and Immunology IZI, Department of Drug Design and Target Validation MWT, Weinbergweg 22, 06120 Halle (Saale), GermanyFraunhofer Institute for Cell Therapy and Immunology IZI, Department of Drug Design and Target Validation MWT, Weinbergweg 22, 06120 Halle (Saale), GermanyPerioTrap Pharmaceuticals GmbH, Weinbergweg 22, 06120 Halle (Saale), GermanyPeriodontitis is a severe yet underestimated oral disease. Since it is linked to several systemic diseases, such as diabetes, artheriosclerosis, and even Alzheimer’s disease, growing interest in treating periodontitis has emerged recently. The major cause of periodontitis is a shift in the oral microbiome. A keystone pathogen that is associated with this shift is <i>Porphyromonas gingivalis</i>. Hence, targeting <i>P. gingivalis</i> came into focus of drug discovery for the development of novel antiinfective compounds. Among others, glutaminyl cyclases (QCs) of oral pathogens might be promising drug targets. Here, we report the discovery and structure–activity relationship of a novel class of <i>P. gingivalis</i> QC inhibitors according to a tetrahydroimidazo[4,5-<i>c</i>]pyridine scaffold. Some compounds exhibited activity in the lower nanomolar range and thus were further characterized with regard to their selectivity and toxicity.https://www.mdpi.com/1424-8247/14/12/1206PgQC<i>Porphyromonas gingivalis</i>periodontitisglutaminyl cyclase |
| spellingShingle | Daniel Ramsbeck Nadine Taudte Nadine Jänckel Stefanie Strich Jens-Ulrich Rahfeld Mirko Buchholz Tetrahydroimidazo[4,5-<i>c</i>]pyridine-Based Inhibitors of <i>Porphyromonas gingivalis</i> Glutaminyl Cyclase Pharmaceuticals PgQC <i>Porphyromonas gingivalis</i> periodontitis glutaminyl cyclase |
| title | Tetrahydroimidazo[4,5-<i>c</i>]pyridine-Based Inhibitors of <i>Porphyromonas gingivalis</i> Glutaminyl Cyclase |
| title_full | Tetrahydroimidazo[4,5-<i>c</i>]pyridine-Based Inhibitors of <i>Porphyromonas gingivalis</i> Glutaminyl Cyclase |
| title_fullStr | Tetrahydroimidazo[4,5-<i>c</i>]pyridine-Based Inhibitors of <i>Porphyromonas gingivalis</i> Glutaminyl Cyclase |
| title_full_unstemmed | Tetrahydroimidazo[4,5-<i>c</i>]pyridine-Based Inhibitors of <i>Porphyromonas gingivalis</i> Glutaminyl Cyclase |
| title_short | Tetrahydroimidazo[4,5-<i>c</i>]pyridine-Based Inhibitors of <i>Porphyromonas gingivalis</i> Glutaminyl Cyclase |
| title_sort | tetrahydroimidazo 4 5 i c i pyridine based inhibitors of i porphyromonas gingivalis i glutaminyl cyclase |
| topic | PgQC <i>Porphyromonas gingivalis</i> periodontitis glutaminyl cyclase |
| url | https://www.mdpi.com/1424-8247/14/12/1206 |
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