Biological evaluation and molecular docking. studies of nitro benzamide derivatives with respect to in vitro anti-inflammatory activity
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Tarih
2017
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Elsevier
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
A series of nitro substituted benzamide derivatives were synthesized and evaluated for their potential anti-inflammatory activities in vitro. Firstly, all compounds (1-6) were screened for their inhibitory capacity on LPS induced nitric oxide (NO) production in RAW264.7 macrophages. Compounds 5 and 6 demonstrated significantly high inhibition capacities in a dose-dependent manner with IC50 values of 3.7 and 53 mu M, respectively. These two compounds were also accompanied by no cytotoxicity at the studied concentrations (max 50 mu M) in macrophages. Molecular docking analysis on iNOS revealed that compounds 5 and 6 bind to the enzyme more efficiently compared to other compounds due to having optimum number of nitro groups, orientations and polarizabilities. In addition, 5 and 6 demonstrated distinct regulatory mechanisms for the expression of the iNOS enzyme at the mRNA and protein levels. Specifically, both suppressed expressions of COX-2, IL-1 beta and TNF-alpha significantly, at 10 and 20 mu M. However, only compound 6 significantly and considerably decreased LPS-induced secretion of IL-1 beta and TNF-alpha. These results suggest that compound 6 may be a multi-potent promising lead compound for further optimization in structure and as well as for in vivo validation studies. (C) 2016 Published by Elsevier B.V.
Açıklama
Anahtar Kelimeler
Nitro substituted benzamides, Anti-inflammatory, Nitric oxide, iNOS, Molecular docking
Kaynak
International Immunopharmacology
WoS Q Değeri
Q2
Scopus Q Değeri
Q1
Cilt
43
