The main limitation in the use of anti-inflammatory drugs or drugs that inhibit some aspects of inflammation is their secondary effects, especially on the gastro-intestinal tract, during chronic use. Therefore, anti-inflammatory drugs without such effects have been one of the main objectives of researchers.
1)Modern organic chemistry development has provided an increased number of substances for various therapeutic aims. Among the methods for obtaining new drugs, molecular modification or variation using the Bioisostery concept is often used. Using this chemical concept, substitute groups can be introduced in one or more positions of a main molecule, creating similar compounds with varied biological activities that can show interesting medical properties. With this process, we can analyze the influence of the modification of an atom or a group of atoms on the main molecule's biological activity. The molecular alterations can result in molecules with similar, antagonistic or more larger potent activity than that of the original compound.2)The thiazolidinic and imidazolidinic nuclei represent a category of compounds that present promising biological activities: insecticidal, 3) antimicrobial, antifungal, narcotic, sedative, anesthetic, anticonvulsive and nematocidal. 4) Góes et al. (1991) 5) showed that thiazolidine and imidazolidine derivatives (or isosters) possess antifungal (against Candida albicans and Neurospora crassa) and moderate antibiotic activity (against E. coli, S. aureus and others).Among the compounds that possess a thiazolidinic nucleus, 2,4-thiazolidinedione ( Fig. 1) and rhodanine (Fig. 2) were studied by Lima (1999) 6) with respect to the antiedematogenic properties of their isosters. In this study antiedematogenic activity was found for two bioisosters, N-tryptophyl-5-(3,5-di-tert-butyl-4-hydroxybenzylidene)-2,4-thiazolidinedione (GS28) (MWϭ476) (Fig. 3) and N-tryptophyl-5-(3,5-di-tert-butyl-4-hydroxybenzylidene) rhodanine (GS26) (MWϭ492) (Fig. 4). Studies related to acute toxicity (LD 50 ) of GS26 and GS28 in a range of oral doses of 25, 50, 100, 250, 500 and 1000 mg/kg did not indicate any toxicity. The aim of this study was to determine the existence of antiedematogenic properties on thiazolidinic isosters GS26 and GS28 in the response evoked by well-known edematogenic agents.
Chemistry Two new compounds N-tryptophyl-5-(3,5-di-