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Start Over Author "Cantelmo, AR" Publisher american chemical society
2 results on '"Cantelmo, AR"'

1. N-O-Isopropyl Sulfonamido-Based Hydroxamates as Matrix Metalloproteinase Inhibitors: Hit Selection and in Vivo Antiangiogenic Activity

Author

Nuti, E, Cantelmo, A, Gallo, C, Bruno, A, Bassani, B, Camodeca, C, Tuccinardi, T, Vera, L, Orlandini, E, Nencetti, S, Stura, E, Martinelli, A, Dive, V, Albini, A, Rossello, A, Nuti E, Cantelmo AR, Gallo C, Bruno A, Bassani B, Camodeca C, Tuccinardi T, Vera L, Orlandini E, Nencetti S, Stura EA, Martinelli A, Dive V, Albini A, Rossello A, Nuti, E, Cantelmo, A, Gallo, C, Bruno, A, Bassani, B, Camodeca, C, Tuccinardi, T, Vera, L, Orlandini, E, Nencetti, S, Stura, E, Martinelli, A, Dive, V, Albini, A, Rossello, A, Nuti E, Cantelmo AR, Gallo C, Bruno A, Bassani B, Camodeca C, Tuccinardi T, Vera L, Orlandini E, Nencetti S, Stura EA, Martinelli A, Dive V, Albini A, and Rossello A

Abstract

Matrix metalloproteinases (MMPs) have been shown to be involved in tumor-induced angiogenesis. In particular, MMP-2, MMP-9, and MMP-14 have been reported to be crucial for tumor angiogenesis and the formation of metastasis, thus becoming attractive targets in cancer therapy. Here, we report our optimization effort to identify novel N-isopropoxy-arylsulfonamide hydroxamates with improved inhibitory activity toward MMP-2, MMP-9, and MMP-14 with respect to the previously discovered compound 1. A new series of hydroxamates was designed, synthesized, and tested for their antiangiogenic activity using in vitro assays with human umbilical vein endothelial cells (HUVECs). A nanomolar MMP-2, MMP-9, and MMP-14 inhibitor was identified, compound 3, able to potently inhibit angiogenesis in vitro and also in vivo in the matrigel sponge assay in mice. Finally, X-ray crystallographic and docking studies were conducted for compound 3 in order to investigate its binding mode to MMP-9 and MMP-14.

Published
2015

2. N-O-Isopropyl Sulfonamido-Based Hydroxamates as Matrix Metalloproteinase Inhibitors: Hit Selection and in Vivo Antiangiogenic Activity.

Author

Nuti E, Cantelmo AR, Gallo C, Bruno A, Bassani B, Camodeca C, Tuccinardi T, Vera L, Orlandini E, Nencetti S, Stura EA, Martinelli A, Dive V, Albini A, and Rossello A

Subjects
Angiogenesis Inhibitors chemical synthesis, Angiogenesis Inhibitors pharmacology, Animals, Apoptosis drug effects, Cell Movement drug effects, Cell Survival drug effects, Crystallography, X-Ray, Human Umbilical Vein Endothelial Cells cytology, Human Umbilical Vein Endothelial Cells drug effects, Human Umbilical Vein Endothelial Cells physiology, Humans, Hydroxamic Acids chemical synthesis, Hydroxamic Acids pharmacology, Matrix Metalloproteinase 14 chemistry, Matrix Metalloproteinase 14 metabolism, Matrix Metalloproteinase 2 chemistry, Matrix Metalloproteinase 2 metabolism, Matrix Metalloproteinase 9 chemistry, Matrix Metalloproteinase 9 metabolism, Matrix Metalloproteinase Inhibitors chemical synthesis, Matrix Metalloproteinase Inhibitors pharmacology, Mice, Molecular Docking Simulation, Stereoisomerism, Structure-Activity Relationship, Sulfonamides chemical synthesis, Sulfonamides pharmacology, Angiogenesis Inhibitors chemistry, Hydroxamic Acids chemistry, Matrix Metalloproteinase Inhibitors chemistry, Sulfonamides chemistry
Abstract

Matrix metalloproteinases (MMPs) have been shown to be involved in tumor-induced angiogenesis. In particular, MMP-2, MMP-9, and MMP-14 have been reported to be crucial for tumor angiogenesis and the formation of metastasis, thus becoming attractive targets in cancer therapy. Here, we report our optimization effort to identify novel N-isopropoxy-arylsulfonamide hydroxamates with improved inhibitory activity toward MMP-2, MMP-9, and MMP-14 with respect to the previously discovered compound 1. A new series of hydroxamates was designed, synthesized, and tested for their antiangiogenic activity using in vitro assays with human umbilical vein endothelial cells (HUVECs). A nanomolar MMP-2, MMP-9, and MMP-14 inhibitor was identified, compound 3, able to potently inhibit angiogenesis in vitro and also in vivo in the matrigel sponge assay in mice. Finally, X-ray crystallographic and docking studies were conducted for compound 3 in order to investigate its binding mode to MMP-9 and MMP-14.

Published
2015
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