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Evaluation and in vivo efficacy study of pyrano[3,2‐c]quinoline analogues as TNF‐α inhibitors
Author(s) -
Upadhyay Kuldip D.,
Dodia Narsinh M.,
Khunt Rupesh C.,
Chaniara Ravi S.,
Shah Anamik K.
Publication year - 2019
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.13566
Subject(s) - in vivo , chemistry , pharmacology , ketamine , xylazine , medicine , anesthesia , biology , microbiology and biotechnology
A series of pyrano[3,2 c]quinoline was evaluated for its in vivo efficacy as TNF ‐α inhibitor using LPS , phosphodiesterase (PDE)‐4, and CIA assays in different mice/rat models. The synthesis was performed using one‐pot multicomponent condensation between 2,4‐dihydroxy‐1‐methylquinoline, malononitrile, and diverse un(substituted) aromatic aldehydes. In vivo efficacy of the title compounds was evaluated using LPS assay in BALB /c mice, PDE 4 inhibition in ketamine–xylazine‐induced anesthetize SD rats, and CIA assay was performed in DBA /1J mice as per the standard literature protocols. The outcome of the study revealed that compound 4v was found to be most promising candidate of the series. It was efficacious with 48.8 ± 13.0% inhibition of TNF ‐α release at 100 mg/kg p.o., in the LPS assay in Balb/c mice model. It was effective in PDE 4 assay in ketamine–xylazine‐induced anesthetize SD rats with duration of 38.3 ± 4.5 min for reversal of anesthetic effect and also showed significant inhibition of PDE 4 in salbutamol treated U937 cell assay. It was also abolished TNF ‐α induced phosphorylation and degradation of IκBα. Ultimately, its effect on CIA ‐related bone and cartilage damage was found statistically similar to Enbrel.