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Structural features and functional activities of benzimidazoles as NOD2 antagonists.
- Source :
-
European journal of medicinal chemistry [Eur J Med Chem] 2020 Mar 15; Vol. 190, pp. 112089. Date of Electronic Publication: 2020 Jan 24. - Publication Year :
- 2020
-
Abstract
- NOD1 and NOD2 are pattern recognition receptors that have important roles in innate immune responses. Although their overactivation has been linked to a number of diseases, NOD2 in particular remains a virtually unexploited target in this respect, with only one structural class of antagonist reported. To gain insight into the structure-activity relationships of NOD2 antagonists, a series of novel analogs was designed and synthesized, and then screened for antagonist activity versus NOD2, and counter-screened versus NOD1. Compounds 32 and 38 were identified as potent and moderately selective NOD2 antagonists, and 33 and 42 as dual NOD1/NOD2 antagonists, with balanced activities against both targets in the low micromolar range. These data enable in-depth exploration of their structure-activity relationships and provide deeper understanding of the structural features required for NOD2 antagonism.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)
- Subjects :
- Anti-Inflammatory Agents chemical synthesis
Anti-Inflammatory Agents toxicity
Benzimidazoles chemical synthesis
Benzimidazoles toxicity
Drug Design
HEK293 Cells
Humans
Molecular Structure
Nod1 Signaling Adaptor Protein antagonists & inhibitors
Structure-Activity Relationship
Anti-Inflammatory Agents pharmacology
Benzimidazoles pharmacology
Nod2 Signaling Adaptor Protein antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1768-3254
- Volume :
- 190
- Database :
- MEDLINE
- Journal :
- European journal of medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 32014680
- Full Text :
- https://doi.org/10.1016/j.ejmech.2020.112089