Pyridine-Containing Macrocycles Display MMP-2/9 Inhibitory Activity and Distinct Effects on Migration and Invasion of 2D and 3D Breast Cancer Models.

ABSTRACT: The role of metalloproteinases (MMPs) on the migration and invasion of cancer cells has been correlated with tumor aggressiveness, namely with the up-regulation of MMP-2 and 9. Herein, two pyridine-containing macrocyclic compounds, [15]pyN₅ and [16]pyN₅, were synthesized, chemically characterized and evaluated as potential MMP inhibitors for breast cancer therapy using 3D and 2D cellular models. [15]pyN₅ and [16]pyN₅ (5-20 µM) showed a marked inhibition of MMPs activity (100% at concentrations ≥ 7.5 μM) when compared to ARP-100, a known MMP inhibitor. The inhibitory activity of [15]pyN₅ and [16]pyN₅ was further supported through in silico docking studies using Goldscore and ChemPLP scoring functions. Moreover, although no si

SUBMITTER: Proenca S 

PROVIDER: S-EPMC6829403 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature