Effect of the Electronic Structure of Para-Substituted Benzaldehyde Benzohydrazone on Its Antimicrobial Activity: A DFT Analysis

Abstract

Bacillus subtilis is a bacterium that has demonstrated its efficacy across various domains, including industry, agriculture, and commerce, owing to its protective, inhibitory, and biological mechanisms against specific microbes. However, at high concentrations, it can lead to food poisoning and severe infections, resulting in symptoms such as diarrhea and vomiting. Bacterial spores produced by Bacillus subtilis can induce conditions like gas gangrene and tetanus. In this context, benzohydrazones are recognized for their antimicrobial activity, particularly against Bacillus subtilis. This study aims to elucidate the relationship between the electronic structure of para-substituted benzaldehyde benzohydrazone derivatives and their antimicrobial activity. This leads to the proposal of a 2D pharmacophore for predicting the antibacterial activity of these derivatives. The quantitative structure-activity relationship (QSAR) approach employed is the KPG method. The electronic structures were optimized using the density functional theory (DFT) method with the B3LYP functional and the 6-31G (d,p) basis set. Charge and local molecular orbitals were considered in the optimization process. The resulting prediction equation (R=98.95%, R²=97.91%, Adjusted R²=96.76%, F(5,9)=84.52) derived from multiple linear regression provides the basis for the proposed 2D pharmacophore. This equation shows that antimicrobial activity of benzohydrazone derivative is on charge and orbital controlled. This pharmacophore holds potential utility in designing new molecular structures with enhanced activity against Bacillus subtilis