Triazole-Pyridine Dicarbonitrile Targets Phosphodiesterase 4 to Induce Cytotoxicity in Lung Carcinoma Cells.
A549 Cells
Antineoplastic Agents
/ chemical synthesis
Cell Proliferation
/ drug effects
Cyclic Nucleotide Phosphodiesterases, Type 4
/ metabolism
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Humans
Lung Neoplasms
/ drug therapy
Molecular Structure
Nitriles
/ chemistry
Phosphodiesterase 4 Inhibitors
/ chemical synthesis
Pyridines
/ chemistry
Structure-Activity Relationship
Triazoles
/ chemistry
Tumor Cells, Cultured
chemotherapy
cytotoxic
phosphodiesterase 4
synthetic small molecule
Journal
Chemistry & biodiversity
ISSN: 1612-1880
Titre abrégé: Chem Biodivers
Pays: Switzerland
ID NLM: 101197449
Informations de publication
Date de publication:
Sep 2019
Sep 2019
Historique:
received:
01
05
2019
accepted:
09
07
2019
pubmed:
10
7
2019
medline:
18
12
2019
entrez:
10
7
2019
Statut:
ppublish
Résumé
Phosphodiesterase 4 (PDE4) is a key enzyme involved in the hydrolysis of cyclic adenosine monophosphate (cAMP) and widely expressed in several types of cancers. The inhibition of PDE4 results in an increased concentration of intracellular cAMP levels that imparts the anti-inflammatory response in the target cells. In the present report, two series of triazolo-pyridine dicarbonitriles and substituted dihydropyridine dicarbonitriles were synthesized using green protocol (TBAB in refluxed water). We next evaluated the title compounds for their cytotoxicity towards lung cancer (A549) cells and identified 7'-[4-(methylsulfonyl)phenyl]-5'-oxo-1',5'-dihydrospiro[cyclohexane-1,2'-[1,2,4]triazolo[1,5-a]pyridine]-6',8'-dicarbonitrile (5h) and 7'-(1-methyl-1H-imidazol-2-yl)-5'-oxo-1',5'-dihydrospiro[cyclohexane-1,2'-[1,2,4]triazolo[1,5-a]pyridine]-6',8'-dicarbonitrile (5j) as lead analogs with the IC
Identifiants
pubmed: 31287204
doi: 10.1002/cbdv.201900234
doi:
Substances chimiques
Antineoplastic Agents
0
Nitriles
0
Phosphodiesterase 4 Inhibitors
0
Pyridines
0
Triazoles
0
Cyclic Nucleotide Phosphodiesterases, Type 4
EC 3.1.4.17
pyridine
NH9L3PP67S
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1900234Informations de copyright
© 2019 Wiley-VHCA AG, Zurich, Switzerland.
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