Chapter 10: Carbohydrate-containing Matrix Metalloproteinase Inhibitors (MMPIs): A Second Childhood for Sulfonamidic Inhibitors?

Among the plethora of synthetic matrix metalloproteinase inhibitors (MMPIs) reported in the last three decades, a prominent position is enjoyed by sulfonamidic inhibitors, a family of which N-isobutyl-N-[(4-methoxyphenylsulfonyl)glycyl]hydroxamic acid (NNGH) is the most popular progenitor. Great expectations in terms of clinical applicability, and corresponding bitter disappointments, have followed the research endeavors dedicated to this family of structures endowed with nanomolar affinities for MMPIs. Too many failures inhibited the interest of academia and industry rather than MMPs so that sulfonamidic inhibitors and, in general, the whole family of MMPIs, suffered from a drop of attention. Recent advances, however, have shed new light on the structural relationship existing between MMPIs and their hosts, bringing the design of innovative molecules to a new life. Tailored inhibitors overcoming some of the limitations suffered by the original NNGH-related structures have been achieved without compromising the high affinity for MMPs. A deeper structural insight and a new approach to MMP targeting may indeed induce a renaissance for this class of compounds.