# Synthesis and multifaceted exploration of dibenzoxepinones: in vitro antimicrobial and ct-DNA binding, DFT/TD-DFT, molecular docking and simulation studies

## TL;DR

Researchers synthesized new dibenzoxepinone compounds and tested their antimicrobial and DNA-binding properties using various techniques.

## Contribution

The study introduces novel dibenzoxepinone derivatives with demonstrated antimicrobial and DNA-binding potential through a combination of experimental and computational methods.

## Key findings

- Compound 7a showed strong antibacterial and antifungal activity with low MIC values and a large zone of inhibition.
- Molecular docking and MD simulations confirmed stable binding interactions of the compounds with target proteins and DNA.
- UV-Vis and fluorescence studies indicated groove-binding interaction with DNA for compound 7a.

## Abstract

In the present study, ten novel derivatives of dibenzoxepine-11-one, have been synthesized and thoroughly characterized using spectroscopic techniques, including 1H and 13C NMR, FTIR, and HRMS. Density Functional Theory (DFT) calculations were carried out to analyze the geometrical structure and vibrational modes, enabling the identification of the most stable conformation of the lead compound. Time-Dependent DFT (TD-DFT) was employed to investigate the electronic transitions within the UV-Vis spectrum. Molecular docking studies were performed for all derivatives using various target proteins with PDB IDs:IKZN (for E. coli), 1IYL (for C. albicans), and the DNA dodecamer structure (PDB ID: 1BNA). The results revealed favorable binding interactions across all targets. Additionally, molecular dynamics (MD) simulations were conducted for 50 ns using the most promising compound, 7a, confirming the stability of its binding conformation. From in vitro studies, antibacterial activity was assessed for all the synthesized derivatives against Gram-positive strains (B. subtilis, L. rhamnosus) and a Gram-negative strain (E. coli). Compounds 7a, 7b, 7c, 7d, and 7f exhibited strong antibacterial efficacy, with minimum inhibitory concentration (MIC) values of 8 μg ml−1 for E. coli and L. rhamnosus and 16 μg ml−1 for B. subtilis bacterial strains. Additionally, compound 7a exhibited good antifungal activity, with a maximum zone of inhibition of 18 mm against the fungal strain C. albicans. Further UV-Vis absorption and fluorescence quenching studies, conducted for compounds 7a, 7b, and 7e with calf thymus DNA (ct-DNA), suggested a groove-binding interaction. Compound 7a demonstrated the strongest binding affinity, with a binding constant (Kb) of 3.61 × 105 M−1 and a Gibbs free energy change (ΔG) of −31.70 kJ mol−1. Therefore, these novel dibenzoxepine-11-ones derivatives are multifaceted in their action as potential antimicrobial and DNA-binding agents, and will be useful in developing new therapeutics.

In the present study, ten novel derivatives of dibenzoxepine-11-one, have been synthesized and thoroughly characterized using spectroscopic techniques, including 1H and 13C NMR, FTIR, and HRMS.