Newly Synthesized 3-Indolyl Furanoid Inhibits Matrix Metalloproteinase-9 Activity and Prevents Nonsteroidal Anti-inflammatory Drug-Induced Gastric Ulceration.

Indomethacin, a known nonsteroidal anti-inflammatory drug (NSAID) induces gastric inflammation, causing degradation of the extracellular matrix by specific matrix metalloproteinases (MMPs). We investigated the antiulcer efficacy of 3-indolyl furanoids ( and , i.e., methoxy substitution at 4- and 5-positions of the indole ring, respectively), derived from indomethacin. Interestingly, protected against indomethacin-induced gastropathy in vivo by inhibiting MMP-9. Our work established a chemical modification strategy for the development of safer NSAIDs. Moreover, in vitro and in silico studies confirmed that inhibited MMP-9 activity with an IC value of 50 μM by binding to the catalytic cleft of MMP-9, leading to ulcer prevention. Pharmacokinetics was presented as the mean concentration-time profile in the rat plasma, and the extraction efficiency was greater than 70%, showing a of 104.48 μg/mL after 6.0 h () treatment with half-life and area under the curve being 7.0 h and 1273.8 h μg/mL, respectively, indicating the higher antiulcer potency of .