Anti-Inflammatory Activity of Pyrazolo[1,5-a]quinazolines; Molecules; Vol. 29, iss. 11

Anti-Inflammatory Activity of Pyrazolo[1,5-a]quinazolines; Molecules; Vol. 29, iss. 11

Bibliographic Details
Parent link:Molecules.— .— Basel: MDPI AG
Vol. 29, iss. 11.— 2024.— Article number 2421, 24 p.
Other Authors: Crocetti L. Letizia, Khlebnikov A. I. Andrey Ivanovich, Guerrini G. Gabriella, Schepetkin (Shchepyotkin) I. A. Igor Aleksandrovich, Melani F. Fabrizio, Giovannoni M. P. Maria Paola, Quinn M. T. Mark
Summary:Title screen
Chronic inflammation contributes to a number of diseases. Therefore, control of the inflammatory response is an important therapeutic goal. To identify novel anti-inflammatory compounds, we synthesized and screened a library of 80 pyrazolo[1,5-a]quinazoline compounds and related derivatives. Screening of these compounds for their ability to inhibit lipopolysaccharide (LPS)-induced nuclear factor κB (NF-κB) transcriptional activity in human THP-1Blue monocytic cells identified 13 compounds with anti-inflammatory activity (IC50 < 50 µM) in a cell-based test system, with two of the most potent being compounds 13i (5-[(4-sulfamoylbenzyl)oxy]pyrazolo[1,5-a]quinazoline-3-carboxamide) and 16 (5-[(4-(methylsulfinyl)benzyloxy]pyrazolo[1,5-a]quinazoline-3-carboxamide). Pharmacophore mapping of potential targets predicted that 13i and 16 may be ligands for three mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase 2 (ERK2), p38α, and c-Jun N-terminal kinase 3 (JNK3). Indeed, molecular modeling supported that these compounds could effectively bind to ERK2, p38α, and JNK3, with the highest complementarity to JNK3. The key residues of JNK3 important for this binding were identified. Moreover, compounds 13i and 16 exhibited micromolar binding affinities for JNK1, JNK2, and JNK3. Thus, our results demonstrate the potential for developing lead anti-inflammatory drugs based on the pyrazolo[1,5-a]quinazoline and related scaffolds that are targeted toward MAPKs
Текстовый файл
Language:English
Published: 2024
Subjects:
pyrazolo[1,5-a]quinazoline
anti-inflammatory compound
mitogen-activated protein kinase
c-Jun N-terminal kinase
molecular docking
pharmacophore mapping
электронный ресурс
труды учёных ТПУ
Online Access:https://doi.org/10.3390/molecules29112421
Format: Electronic Book Chapter
KOHA link:https://koha.lib.tpu.ru/cgi-bin/koha/opac-detail.pl?biblionumber=683079

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