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Effects of a new 1,3,4‐thiadiazolium mesoionic compound, MI‐D, on the acute inflammatory response
Author(s) -
Cardoso Júlio C.,
Cadena Sílvia M. S. C.,
Zampronio Aleksander,
Arruda Ana Maria S.,
Carnieri Eva G. S.,
Echevarria Aurea,
Constantin Jorgete,
Bracht Adelar,
Oliveira Maria Benigna M.
Publication year - 2004
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.10354
Subject(s) - mesoionic , chemistry , pharmacology , nitric oxide , lipopolysaccharide , antipyretic , endocrinology , medicine , analgesic , organic chemistry , medicinal chemistry
Abstract A new mesoionic compound, 4‐phenyl‐5‐(4‐nitro‐cinnamoyl)‐1,3,4‐thiadiazolium‐2‐phenylamine (MI‐D), is described along with some of its biological properties. Its effects on hepatic metabolism, on O 2 −and nitric oxide (NO) production, and in in vivo models for potential antinociceptive, antipyretic, and antiinflammatory activities were determined. In perfused rat liver, MI‐D (25 µM) stimulated glycogenolysis (95%), and inhibited oxygen uptake (37%) with affecting glycolysis. In phorbol 12‐myristate 13‐acetate‐stimulated macrophages, O 2 −generation was reduced (95%) by MI‐D (15 µM), whereas the production of NO was unaffected. MI‐D (2 mg/kg) inhibited (55%) the number of abdominal writhings induced by acetic acid. At 1 mg/kg, MI‐D inhibited the febrile response (5 h) induced by lipopolysaccharide (LPS) and was also effective against a preexisting febrile response. Treatment with MI‐D (1 mg/kg) reduced by 67% prostaglandin (PGE 2 ) levels in the cerebrospinal fluid of LPS‐exposed mice, and at a higher dose (8 mg/kg) MI‐D inhibited paw edema formation (2 h) induced by carrageenan. MI‐D has a spectrum of activities similar to other nonsteroidal antiinflammatory drugs, qualifying it as a potential anti‐inflammatory drug. Drug Dev. Res. 61:207–217, 2004. © 2004 Wiley‐Liss, Inc.