Design, Synthesis and Characterization of New Acenaphthoquinone derived Halogen-Substituted Oxindole Bis-Schiff Bases: In-Vitro and In-Silico Studies

Abstract

In this study, a new series of halogen-substituted oxindole bis-Schiff base derivatives (5f, 5g, and 5j) were synthesized using a regioselective strategy involving temporary carbonyl protection followed by sequential condensation between halogenated isatin and acenaphthoquinone derivatives. The structural elucidation of the synthesized compounds was confirmed by FT-IR, ¹H NMR, and ¹³C NMR spectral analyses, validating the formation of the bis-imine framework. The antibacterial evaluation revealed that halogen substitution significantly influenced biological activity, with the fluorinated derivative 5g exhibiting superior inhibition against Bacillus subtilis and Escherichia coli.Molecular docking studies performed against DNA gyrase showed strong binding affinities (–5.20 to –5.60 kcal/mol) with key hydrogen bond and hydrophobic interactions involving residues Ala117, Ala118, Tyr86, and Val90, indicating stable enzyme–ligand binding. The pharmacokinetic and ADMET analysis further revealed favourable bioavailability (0.79–0.86), excellent intestinal permeability (HIA = 0.99), appropriate TPSA (70.89 Ų), and satisfactory metabolic stability (half-life ≈ 93–97 h). The combined experimental, docking, and pharmacokinetic results highlight that these halogenated oxindole bis-Schiff bases, particularly compound 5g, possess promising structural and biological characteristics for further optimization as potential antibacterial agents targeting DNA gyrase.