Sulfonamide derivatives with protease inhibitory action as anticancer, anti-inflammatory and antiviral agents

A large number of suffonamide derivatives have ultimately been reported to show substantial protease inhibitory properties. Some matrix metalloprotease (MMP) inhibitors belonging to this class show significant antiturnour properties. Such compounds also lead to the design of effective tumour TNF-alpha converting enzyme (TACE) inhibitors, potentially useful in the treatment of inflammatory states. Since both MMPs and TACE contribute synergistically to the pathophysiology of many diseases (arthritis, bacterial meningitis, tumour invasion etc.), the dual inhibition of these enzymes emerged as an interesting target for the drug design of anticancer/anti-inflammatory drugs. Human neutrophil elastase (HNE) inhibitors of the sulfonamide type may also be useful in the treatment of inflammatory conditions such as emphysema, cystic fibrosis, chronic bronchitis, ischaemia-reperfusion injury and acute respiratory distress syndrome. Inhibition of cysteine proteases, such as several caspase and cathepsin isozymes, may lead to the development of pharmacological agents effective for the management of rheumatoid arthritis, inflammatory bowel disease, brain damage and stroke. Another research line that has progressed recently regards different sulfonamides with remarkable antiviral activity. Some clinically used HIV protease inhibitors, such as amprenavir (Agenerase(TM), Vertex Pharmaceuticals, Inc.), possess sulfonamide moieties in their molecules, whereas a very large number of other derivatives are constantly being synthesised and evaluated in order to obtain compounds with lower toxicity or augmented activity against viruses resistant to the first generation of such drugs.