title: Immunotropic properties of 2-aminobenzimidazole derivatives in cultures of human peripheral blood cells, Part 5.
abstract: The reaction of 2-aminobenzimidazole with selected 4-methoxy-,2,4-dimethoxy-, 4-chloro-, 4-nitro-, and 2-nitrocinnamic acid under different conditions has been described. Two series of derivatives were obtained: 4-aryl-1,2,3,4-tetrahydropyrimido[1,2-a]-benzimidazol-2-ones (1-3) or substituted amides 4, 5, 7. The following compounds: 4-(p-methoxyphenyl)- (1), 4-(2,4-dimethoxyphenyl)- (2), 4-(p-chlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazo l-2-one (3), amides: 2-(p-nitrocinnamoylamino)- (4), 2-(p-methoxycinnamoylamino)-benzimidazole (5), and 3-methyl-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-2-one (6), recently synthesized, have been selected for further studies. Among the studied compounds, 3 and 4 strongly inhibited PHA-induced proliferation of human lymphocytes and weaker, but significantly, MLC-induced lymphocyte proliferation. 3 and 4 inhibited also LPS- or MLC-induced TNF-alpha production. In addition, TNF-alpha production, induced by LPS, was inhibited by compounds 1 and 2. Higher activity of 3 and 4 could be associated with the presence in their structures of -Cl and -NO2 substituents as compared with compounds possessing -OCH3 groups. Compounds 3 and 4 were not toxic when administered orally to mice which predisposes them for further investigations with a chance of clinical application.
authors.affiliation: Department of Technology of Drugs, Wroclaw University of Medicine, Poland.
authors.forename: W
authors.initials: W
authors.lastname: Nawrocka
authors.forename: M
authors.initials: M
authors.lastname: Zimecki
authors.forename: T
authors.initials: T
authors.lastname: Kuznicki
authors.forename: M W
authors.initials: MW
authors.lastname: Kowalska
mesh_terms: D000276:Adjuvants, Immunologic / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: C119689:2-(4-nitrocinnamoylamino)benzimidazole; C119688:4-(4-chlorophenyl)-1,2,3,4-tetrahydropyrimido(1,2-a)benzimidazol-2-one; D000276:Adjuvants, Immunologic; D001562:Benzimidazoles; D015850:Interleukin-6; D011743:Pyrimidines; D014409:Tumor Necrosis Factor-alpha