title: Synthesis and biological evaluation of substituted N-[3-(1H-pyrrol-1-yl)methyl]-1,2,5,6-tetrahydropyridin-1-yl]benzamide/benzene sulfonamides as anti-inflammatory agents.
abstract: The pharmacological activities of tetrahydropyridine (THP) derivatives are dependent on the substituent ring moiety. In this study, we investigate the anti-inflammatory activities of 12 newly synthesized substituted N-[3-(1H-pyrrol-1-yl)methyl]-1,2,5,6-tetrahydrobenzamide/benzene sulfonamides (9a-l) in murine BV-2 microglial cells. All compounds were initially screened for attenuation of nitric oxide (NO) production in lipopolysaccharide (LPS) (1 µg/mL)-activated microglial cells. The data show that only SO2 -substituted THPs were effective at sub-lethal concentrations (IC50 values of 12.92 µM (9i), 14.64 µM (9j), 19.63 µM (9k)) relative to L-N6-(1-iminoethyl)lysine positive control (IC50  = 3.1 µM). The most potent SO2 -substituted compound (9i) also blocked the LPS-inducible nitric oxide synthase (iNOS) and attenuated the release of several cytokines including IL-1α, IL-10, and IL-6. These findings establish the moderate immuno-modulating effects of SO2 -substituted THP derivatives.
authors.affiliation: College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL, USA.
authors.forename: Madhavi
authors.initials: M
authors.lastname: Gangapuram
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Mazzio
authors.forename: Suresh
authors.initials: S
authors.lastname: Eyunni
authors.forename: Karam F A
authors.initials: KF
authors.lastname: Soliman
authors.forename: Kinfe K
authors.initials: KK
authors.lastname: Redda
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D053582:Interleukin-1alpha / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D015394:Molecular Structure; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000235:genetics; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D053582:Interleukin-1alpha; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011743:Pyrimidines; D013449:Sulfonamides; C577686:interleukin-6, mouse; C440499:lipopolysaccharide, Escherichia coli O111 B4; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse
keywords: Cytokines; Drug design; Microglial cells; Nitric oxide; Tetrahydropyridine