Sulphonamides: Deserving class as MMP inhibitors?

The importance of sulphonamide moiety in medicinal chemistry cannot be ignored as it constitutes an important class of extensively used drugs. Recently, sulphonamides have also been reported for their matrix metalloproteinase (MMP) inhibitory activity. MMPs are calcium- and zinc-dependent endopeptidases, involved in both inter- and intra-cellular activity. This review documents the emergence of sulphonamides as matrix metalloproteinase inhibitors (MMPIs) from the first generation to the recent third generation MMPIs, their mode of action – how sulphonamides act on MMPs? as well as the structure activity relationship along with their therapeutic uses in chronic obstructive pulmonary disease (COPD), ulcer, asthma, arthritis and cancer. From this review, readers can get answer for the question- is sulphonamides a potential class of MMPIs?

Sulfonamides inhibit MMPs by forming hydrogen bonds and directing the hydrophobic substituents deeply to the S1′ pocket; thus strengthening their role in disorders like COPD, dermal ulcers, asthma, arthritis, cancer etc.Figure optionsDownload as PowerPoint slideHighlights
► CGS-27023A – prototype sulphonamide MMP inhibitors.
► Development of sulphonamide MMPIs has been discussed from the prototype CGS-27023A to S-3304.
► MMPIs contain Zn-binding motif, connecting scaffold along with S1′ and S2′ binding sites.
► SAR studies have revealed that potent MMPIs with nanomolar inhibition can be obtained.
► Sulphonamides as MMPIs can be useful in COPD, ulcer, arthritis, asthma and cancer.