Synthesis, spectroscopic characterization, DFT analysis, antibacterial, antifungal, antioxidant, molecular docking, and ADME study of 3,4-dihydro-2H-napthalen-1-one tagged chalcone derivatives

Abstract

Chalcone derivatives were synthesized from 3,4-dihydro-2H-naphthalen-1-one using a base-catalyzed Claisen-Schmidt reaction and characterized by FT-IR, ¹H NMR, and ¹³C NMR spectroscopy. Density functional theory (DFT) with the B3LYP/6-311G(d,p) basis set was employed to explore the structural, electronic, and quantum properties of the compounds. Simulated electronic absorption spectra for compounds 3c and 3e in gas phase, DMSO, and DCM were generated using time-dependent DFT (TD-DFT). Compound 3c's first singlet excited state shifted from 376.10 nm in the gas phase to 390.08 nm in DMSO, while compound 3e shifted from 381.58 nm to 383.54 nm in DMSO. Experimental absorption values matched the theoretical predictions, with higher oscillator strengths in DMSO and DCM indicating solvent-enhanced transition probabilities. The antimicrobial activity of the chalcones was evaluated against four bacterial strains (E. coli, B. subtilis, S. aureus, and Streptococcus spp.) and four fungal strains (R. oryzae, P. chrysogenum, A. niger, and C. albicans). Compounds 3d and 3f showed strong antibacterial activity with MIC values of 3.9 µg/mL and moderate antifungal activity. Antioxidant properties were assessed using DPPH and hydroxyl radical assays, with compound 3d demonstrating 75.8 % and 76.4 % scavenging activity for OH and DPPH radicals, respectively. ADME studies were conducted to evaluate pharmacokinetics, and molecular docking studies revealed strong binding affinities. Compounds 3a and 3e had docking scores of -8.7 kcal/mol with the E. coli protein (PDB ID: 1KZN), while 3d and 3f performed best against B. subtilis (PDB ID: 1BAG) and S. aureus gyrase (PDB ID: 2XCT), with scores of -9.1 and -8.3 kcal/mol, respectively. Molecular dynamics simulation of compound 3d with 1BAG over 100 ns confirmed stable binding. These findings suggest chalcone derivatives have strong potential for pharmaceutical development.