title: Synthesized pyridine compound derivatives decreased TNF alpha and adhesion molecules and ameliorated HSV-induced inflammation in a mouse model.
abstract: Synthesized pyridine compound derivatives (SK94, SK126) from a natural lead source were administered to mice to test for possible anti-TNF alpha and anti-inflammatory activities. Lipopolysaccharide (LPS)-induced TNF alpha production was analyzed in the endothelial cells, Raw 264.7 cells, and serum of normal mice after treatment with SK compounds. These compounds were also orally administered to a herpes simplex virus (HSV)-induced Behcet's disease mouse model to investigate their anti-inflammatory therapeutic effect. TNF alpha production was inhibited in a dose-dependent manner in the SK94 treated cells. E-selectin, VCAM-1, and ICAM-1 mRNA levels were also down-regulated. Treatment with 30mg/kg SK94 inhibited 55% of the TNF alpha production in LPS challenged Balb/c mice (n=8). SK94 and SK126 were administered to the Behcet's disease-like mice for five consecutive days and SK94 improved in five out of six mice (83%), while it only improved in one out of nine mice (11%) in the pH 1.2 saline (artificial gastric juice) group (P<0.005), four out of ten mice (40%) in the thalidomide group (P<0.05), and six out of seven (86%) in the SK126 group (P<0.005). Soluble ICAM-1 was inhibited by 23.8% in the sera of SK94 treated mice and by 34.6% in SK126 treated mice when compared to artificial gastric juice. Based on these findings, SK compounds could be candidates for clinical trials.
authors.affiliation: Laboratory of Cell Biology, Ajou University Institute for Medical Sciences, Republic of Korea.
authors.forename: Bunsoon
authors.initials: B
authors.lastname: Choi
authors.forename: Joohyon
authors.initials: J
authors.lastname: Kim
authors.forename: Eun-So
authors.initials: ES
authors.lastname: Lee
authors.forename: Dongsik
authors.initials: D
authors.lastname: Bang
authors.forename: Seonghyang
authors.initials: S
authors.lastname: Sohn
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001528:Behcet Syndrome / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000821:virology*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008970:Molecular Weight; D009287:Naphthyridines / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011725:Pyridines / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018139:Simplexvirus / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: C528322:2-ethyl-8-(4-fluorophenyl)-6-methyl-3,4-dihydro-2H-(2,7)naphthyridin-1-one; D015815:Cell Adhesion Molecules; D009287:Naphthyridines; D011725:Pyridines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C023666:pyridine