Design, Synthesis and Therapeutic investigation of Tryptamine derivatives as Potential Antioxidant and Amyloid inhibitor/disaggregator

Abstract

Oxidative stress is one of the main causative factors for pathogenesis of numerous disorders including psychological and neurodegenerative diseases (Alzheimer’s disease and Parkinsonism). Amyloid aggregates induced oxidative stress is involved in disfunction and degeneration of brain cells in Alzheimer’s disease. Antioxidants are important natural or synthetic molecules having tendency to curb free radicals and discontinuing their chain reactions prior to the damage of essential biomolecules. Drugs possessing antioxidant activity are being extensively anticipated for developing novel therapeutic agents in numerous pathological conditions accompanying oxidative stress like AD. In this study twelve tryptamine derivatives were synthesized and investigated for antioxidant, fibril inhibition and disaggregation potential. In vitro antioxidant potential of the derivatives was examined by using DPPH (2,2‑diphenyl‑1‑picrylhydrazyl) assay and revealed that SR10, SR14, SR23 and SR42 displayed better antioxidant activity (IC50 in the range of 0.75±0.05µM-14.43±0.77µM) than the standard ascorbic acid (IC50 =15.83±0.88µM). In vitro amyloid fibril inhibition and disaggregation assay was carried out by using HEWL (Hen egg white lysozyme) presenting moderate to high inhibition/disaggregation activities. Molecular dockingassessment recognized themode of bindingswithin active site of human antioxidant enzyme peroxiredoxin (PDB ID: 3MNG). These tryptamine derivatives with potential antioxidant and inhibition/disaggregation activitieswill be beneficialto develop and designdrug molecules forneurodegenerative disorders.