Synthesis of Biologically Active Novel Indole Fused Heterocyclic Derivatives: Molecular Modeling Studies

Abstract

A novel series of fluoro/methoxy indole analogues 6 was synthesized and the final targets were confirmed by IR, ¹H & ¹³C NMR and mass spectral analysis. Novel 3-substituted indole derivatives estimate for their antibacterial, antioxidant activities particularly the parent core combined with benzamides ring significantly. From antibacterial activities, compounds 6c, 6e and 6b show the highest bacterial activity against S. epidermidis, S. aureus, E. coli, with zone of inhibition 34, 30, 28 mm, respectively. Novel fluoroindole derivatives 6c, 6b, 6i shows an excellent antioxidant activity with % of inhibition 150.12, 139.04, 137.08 mmol/mL, respectively. The calculations for ligand-protein flexible of crystal structure of C(30) carotenoid dehydrosqualene synthase from S. aureus complexed with bisphosphonate BPH-700 (2ZCS). Among the designed compounds 6c exhibited highest hydrogen bonding interactions 2.06 Å, 1.85 Å with amino acids Asp27, Lys273 and binding energy -6.38 kcal/mol, respectively. Fluoroindoles 6i, 6e and 6f shows highest ΔG = -7.90, -7.66, -7.47 kcal/mol with dissociation constants 10.32, 21.77, 22.68 μM and amino acid Lys273 interactions.