Novel 5 ‐Hydroxy, 5‐Substituted Benzenesulfonamide Pyrimidine‐2,4,6‐Triones Attenuate Lipopolysaccharide‐Induced Acute Lung Injury via Inhibition of the Gelatinases, MMP‐2 and MMP‐9

ABSTRACT A novel series of ten 5‐hydroxy, 5‐substituted benzene sulfonamide pyrimidine‐2,4,6‐triones were synthesized and their structures ascertained using 1H‐NMR, 13C‐NMR, mass and elemental analysis. These compounds were subsequently tested for inhibition of MMP‐2 and MMP‐9 where most exhibited activity with compound 5i being the most potent against MMP‐2 and MMP‐9 with IC50 values of 2.35 nM and 8.24 nM, respectively. Compound 5i was further analyzed in a mouse LPS‐induced acute lung injury model where it had protective activity. Histochemical studies indicated that 5i improved the vascular integrity of the lung.
Source: Drug Development Research - Category: Drugs & Pharmacology Authors: Tags: Research Article Source Type: research