Radical Quenching and LOX Inhibiting Properties of Indole Derivatives: A Plausible Mechanism of Action Through HAT,...

A series of 2-phenylindoles were synthesized and studied the radical quenching properties towards compounds with nitrogen radical. The present indoles exhibit radical quenching properties in a substituent dependent manner through proton and electron transfer mechanisms. ortho-Hydroxy-2-phenylindole and para-hydroxy-2-phenylindole show strong radical quenching properties towards DPPH radical as comparable to vitamin C, whereas meta-hydroxy-2-phenylindole and 2-phenylindole exhibit radical quenching properties with lower efficacy. All these indoles, however, exhibit efficient radical quenching properties towards ABTS radical as comparable to DPPH radical (IC₅₀ towards DPPH/ABTS: 1: 335/22 µM, 2: 15/7 µM, 3: 102/8 µM, 4: 9/10 µM, vitamin C: 10/3 µM). These compounds also bind to lipoxygenase (LOX) and inhibit LOX activity with IC₅₀ : 18-44 µM. It is shown that O-H bond dissociation energy and ionization energy play important role in deciding the radical quenching properties of present indole compound. The compound-LOX binding affinity and binding interface is computed through autodock vina. The indole-LOX binding interface comprises of hydrophobic amino acid residues. In the presence of. indole molecule, the radical quenching occurs through hydrogen atom and/or through electron and subsequently proton transfer mechanism.