Anti-arthritic properties

A new class of compounds is reported to have dual inhibitory properties. They have a y-sultam skeleton and show potent inhibitory effects towards both COX-2 and 5-lipoxygenase as well as production of IL-1 in in vitro assays. These compounds have also proved to be effective in several animal arthritic models without any ulcerogenic activity. Among these compounds S-2474 ((E)-(5)-(3,5-di-fe/t.-butyl-4-hydroxy-benzylidene)-2-ethyl-1,2-isothiazolidine-1,1-dioxide) was selected as an anti-arthritic drug candidate and is now under clinical investigations (Inagaki et al., 2000). 

Introduction of the 16a-hydroxyl group into 9-fluoro-hydrocortisone and 9-fluoro-prednisolone has been shown by Bernstein et al. [16] to result in complete suppression of the salt-retaining properties of these steroids, without appreciably impairing their glucocorticoid activity. Moreover, studies in man have demonstrated the anti-arthritic activity of 9-fluoro-16a-hydroxy-prednisolone and have confirmed its lack of salt-retaining activity. Subsequently, Lederle reported that the anti-inflammatory potency was lowered, but salt retention was eliminated. 

Collagenase production and release are partly responsible for the joint destruction that characterises human rheumatoid arthritis. Triterpenes from the lupane and a-amyrin groups have been studied in vitro to examine their effects on the release of the arthritic joint degradative enzyme collagenase using the rat osteosarcoma. This test and the rat synovial granuloma of adjuvant arthritis are similar both models are based on connective tissue tumours with bone-invasive properties. The pentacyclic triterpenes assayed have been shown to possess general antiproteolytic effects that can explain the anti-arthritic effects in adjuvant arthritis in rats [71,103]. 

The separation of nonsteroidal anti-inflammatory drugs (NSAIDs) has recently attracted considerable interest. Nonsteroidal anti-inflammatory drugs are agents that, in addition to having anti-inflammatory action, also have analgesic, antipyretic, and platelet-inhibitory properties. They are used primarily in the treatment of chronic arthritic conditions and certain soft tissue disorders associated with pain and inflammation. 

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