Synthesis and Biological Assessment of Pyrrolobenzoxazine Scaffold as a Potent Antioxidant

Reduction of mitochondrial
oxidative stress-mediated diseases is
an important pharmaceutical objective in recent biomedical research.
In this context, a series of novel pyrrolobenzoxazines (PyBs) framework
with enormous diversity (compounds 5a–w) was synthesized by employing a low-temperature greener pathway,
and antioxidant property of the synthesized compounds was successfully
demonstrated on preclinical model goat heart mitochondria, in vitro. Copper–ascorbate (Cu–As) was utilized
as an oxidative stress generator. Out of screened PyBs, the compound
possessing −OH and −OMe groups on benzene nucleus along
with pyrrolobenzoxazine core moiety (compound 5w) displayed
magnificent antioxidant property with a minimum effective dose of
66 μM during the biochemical assessment. The ameliorative effect
of synthesized pyrrolobenzoxazine moiety on levels of biomarkers of
oxidative stress, antioxidant enzyme, activities of Krebs cycle and
respiratory chain enzymes, mitochondrial morphology, and Ca2+ permeability of mitochondrial membrane was investigated in the presence
of Cu–As. Furthermore, the binding mode of Cu–As by
compound 5w was explored successfully using isothermal
titration calorimetry (ITC) analysis.