title: Biological evaluation and molecular docking studies of nitro benzamide derivatives with respect to in vitro anti-inflammatory activity.
abstract: 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 IC50values of 3.7 and 5.3μM, respectively. These two compounds were also accompanied by no cytotoxicity at the studied concentrations (max 50μM) 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-1β and TNF-α significantly, at 10 and 20μM. However, only compound 6 significantly and considerably decreased LPS-induced secretion of IL-1β and TNF-α. 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.
authors.affiliation: Department of Molecular Biology & Genetics, Faculty of Art and Science, Çanakkale Onsekiz Mart University, Terzioğlu, 17020 Çanakkale, Turkey. Electronic address: tumerb@gmail.com.
authors.forename: Tugba B
authors.initials: TB
authors.lastname: Tumer
authors.affiliation: Natural Products and Drug Research Laboratory, Department of Chemistry, Faculty of Art and Science, Çanakkale Onsekiz Mart University, Terzioğlu, 17020 Çanakkale, Turkey.
authors.forename: Ferah Comert
authors.initials: FC
authors.lastname: Onder
authors.affiliation: Department of Molecular Biology & Genetics, Faculty of Art and Science, Çanakkale Onsekiz Mart University, Terzioğlu, 17020 Çanakkale, Turkey.
authors.forename: Hande
authors.initials: H
authors.lastname: Ipek
authors.affiliation: Natural Products and Drug Research Laboratory, Department of Chemistry, Faculty of Art and Science, Çanakkale Onsekiz Mart University, Terzioğlu, 17020 Çanakkale, Turkey.
authors.forename: Tugba
authors.initials: T
authors.lastname: Gungor
authors.affiliation: Department of Molecular Biology & Genetics, Faculty of Art and Science, Çanakkale Onsekiz Mart University, Terzioğlu, 17020 Çanakkale, Turkey.
authors.forename: Seda
authors.initials: S
authors.lastname: Savranoglu
authors.affiliation: Department of Chemistry, Faculty of Art and Science, Gaziantep University, Şehitkamil, 27310 Gaziantep, Turkey.
authors.forename: Tugba Taskin
authors.initials: TT
authors.lastname: Tok
authors.affiliation: Department of Chemistry, Faculty of Science, Gebze Technical University (GTU), Gebze, 41400 Kocaeli, Turkey.
authors.forename: Ayhan
authors.initials: A
authors.lastname: Celik
authors.affiliation: Natural Products and Drug Research Laboratory, Department of Chemistry, Faculty of Art and Science, Çanakkale Onsekiz Mart University, Terzioğlu, 17020 Çanakkale, Turkey. Electronic address: mehmetay06@comu.edu.tr.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Ay
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001549:Benzamides / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival; D051546:Cyclooxygenase 2 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000737:chemistry / Q000378:metabolism*; D009574:Nitro Compounds / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D000067996:RAW 264.7 Cells; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D001549:Benzamides; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D009574:Nitro Compounds; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C037689:benzamide; D052247:Nitric Oxide Synthase Type II; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2
keywords: Anti-inflammatory; Molecular docking; Nitric oxide; Nitro substituted benzamides; iNOS