Synthesis and Biological Assessment of Pyrrolobenzoxazine Scaffold as a Potent Antioxidant.
Tania KunduBharati BhattacharjeeSubhenjit HazraArnab K GhoshDebasish BandyopadhyayAnimesh PramanikPublished in: Journal of medicinal chemistry (2019)
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.
Keyphrases
- oxidative stress
- diabetic rats
- ischemia reperfusion injury
- dna damage
- induced apoptosis
- oxide nanoparticles
- anti inflammatory
- heart failure
- metal organic framework
- aqueous solution
- endothelial cells
- stem cells
- signaling pathway
- transcription factor
- atomic force microscopy
- high speed
- cell therapy
- protein kinase
- tissue engineering