Effects of a new 1,3,4-thiadiazolium mesoionic compound, MI-D, on the acute inflammatory response

• Published in: Drug development research Vol. 61; no. 4; pp. 207 - 217
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-04-2004; Wiley-Liss
• Subjects: 4-thiadiazolium; antiinflammatory activity; Biological and medical sciences; cyclooxygenase; Medical sciences; mesoionic 1; mesoionic 1,3,4‐thiadiazolium; Pharmacology. Drug treatments; Prostaglandin-endoperoxide synthase; Enzyme; Acute; mesoionic 1,3,4-thiadiazolium; Antiinflammatory agent; Mesoionic compound; cyclooxygenase; Inflammation; Oxidoreductases; antiinflammatory activity; Biological activity
• ISSN: 0272-4391; 1098-2299
• DOI: 10.1002/ddr.10354

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 (PGE2) 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.