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Immunotropic Properties of 2‐Aminobenzimidazole Derivatives in Cultures of Human Peripheral Blood Cells, Part 5
Author(s) -
Nawrocka Wanda,
Zimecki Michal,
Kuznicki Tomasz,
Kowalska Maria Wiktoria
Publication year - 1999
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/(sici)1521-4184(19993)332:3<85::aid-ardp85>3.0.co;2-s
Subject(s) - chemistry , benzimidazole , aryl , nitro , stereochemistry , peripheral blood , chemical synthesis , medicinal chemistry , pharmacology , in vitro , biochemistry , organic chemistry , immunology , medicine , alkyl
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 deriva‐tives 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 ]benzimidazol‐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‐α production. In addition, TNF‐α 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 ‐NO 2 substituents as compared with compounds possessing ‐OCH 3 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.