Matrix metalloproteinases (MMPs) are an important family of zinc-containing enzymes with a central role in many physiological and pathological processes. Although several MMP inhibitors have been synthesized over the years, none reached the market because of off-target effects, due to the presence of a zinc binding group in the inhibitor structure. To overcome this problem non-zinc-binding inhibitors (NZIs) have been recently designed. In a previous article, a virtual screening campaign identified some hydroxynaphtyridine and hydroxyquinoline as MMP-2 non-zinc-binding inhibitors. In the present work, simplified analogues of previously-identified hits have been synthesized and tested in enzyme inhibition assays. Docking and molecular dynamics studies were carried out to rationalize the activity data.
Ammazzalorso, A., De Filippis, B., Campestre, C., Laghezza, A., Marrone, A., Amoroso, R., … Agamennone, M. (2016). Seeking for non-zinc-binding MMP-2 inhibitors: Synthesis, biological evaluation and molecular modelling studies. International Journal of Molecular Sciences, 17(10). https://doi.org/10.3390/ijms17101768