Synthesis, Drug-Likeness Evaluation of Some Heterocyclic Moieties Fused Indole Derivatives as Potential Antioxidants

Background: Indole and its derivatives have a wide range of pharmacological effects, including analgesic, antimicrobial, antidepressant, anti-diabetic, anti-convulsant, anti-helminthic, and anti-inflammatory properties. They are crucial structural components of many of today's powerful antioxidant medications. Objective: Using the Schotten–Baumann reaction, the indole ring was linked to other key heterocyclic moieties such as morpholine, imidazole, piperidine, and piperazine at the active 3^rd position and then tested for antioxidant activity. Methods: Synthesis of derivatives was accomplished under appropriate conditions and characterized by IR, NMR (¹H and ¹³C), and mass spectrum. Using the Swiss ADME online application, ADME properties were also determined. The in vitro antioxidant activity was measured using DPPH and Reducing power method. Results: In the DPPH assay, compounds 5a (IC50=1.01±0.22 μg/mL), 5k (IC50=1.21 ± 0.07 μg/mL), whereas compounds 5a (EC50=23 ± 1.00 μg/mL), 5h (EC50=26±2.42 μg/mL) in the reducing power assay were most potent as compared with standard Ascorbic acid. Compounds 5a, 5h, and 5k demonstrated maximal potency equivalent to standard. Lipinski's rule was followed in ADME outcomes. Conclusion: The synthesis and evaluation of indole derivatives to investigate their antioxidant action has received a lot of attention. These discoveries could lead to more effective antioxidant candidates being designed and developed.