Antiedematogenic activity of two thiazolidine derivatives: N-tryptophyl-5-(3,5-di-tert-butyl-4-hydroxybenzylidene) rhodanine (GS26) and N-tryptophyl-5-(3,5-di-tert-butyl-4-hydroxybenzylidene)-2,4-thiazolidinedione (GS28).
The search for new anti-inflammatory drugs has been constant in several research centers. The use of the Bioisostery concept allows the elaboration of new bioactive compounds with different properties through the introduction of substitute groups in one or more positions of a main molecule with known biological activity. Preliminary works accomplished at our laboratory with 2,4-thiazolidinedione isosters demonstrated inhibitory activity on edema formation for N-tryptophyl-5-(3,5-di-tert-butyl-4-hydroxybenzylidene)-2,4-thiazolidinedione (GS28) and N-tryptophyl-5-(3,5-di-tert-butyl-4-hydroxybenzylidene) rhodanine (GS26). We verified the antiedematogenic and ulcerogenic activity of these two compounds in Wistar rats. The carrageenan induced paw edema suffered significant (p<0.05) inhibition (28.36% on average) for GS28 (100 mg/kg; v.o.) during the entire time of the experiment. GS26 (50 and 100 mg/kg; v.o.) significantly inhibited (p<0.05) the paw edema dextran induced (22.1 and 27.8%, for the respective doses) after 180 min. The compounds GS26 and GS28 did not show ulcerogenic activity on gastric mucous. The results suggest antiedematogenic action for both compounds without the appearance of gastric lesions.
Rodrigues e Silva
Antonio Alfredo
AA
Department of Physiology and Pharmacology, Federal University of Pernambuco, Recife, Brazil.
da Silva Góes
Alexandre José
AJ
de Lima
Waldir Tavares
WT
de Souza Maia
Maria Bernadete
MB
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012236:Rhodanine / Q000737:chemistry / Q000627:therapeutic use*; D013276:Stomach Ulcer / Q000188:drug therapy* / Q000473:pathology; D045162:Thiazolidinediones / Q000737:chemistry / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D045162:Thiazolidinediones; D012236:Rhodanine; C089946:2,4-thiazolidinedione