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.

A DFT study of the relationships between electronic structure and inhibitory effects of caffeine derivatives on neoplastic transformation was carried out. We obtain one statistically significant equation (R=0.97, R²= 0.94, adjusted R²= 0.92, F(7,34) =71.40 (p<0.00001), SD=0.14), relating the variation of the biological activity with the variation of the values of a definite set of local atomic reactivity indices. Based on the analysis of the results, a partial pharmacophore was built that can be employed as a tool for the development of more active molecules. Calculations have been performed by DFT/B3LYP method in the 6-31G orbital basis set.

Malaria is a serious health problem in Africa and other poor regions of the world, where new anti-malarial drugs are urgently needed at a price affordable to all. This theoretical study on the relationship between the electronic structure and the anti-malarial activity of a series of 4-quinolinylhydrazone derivatives on a chloroquine-resistant strain (K1) is carried out with the aim of proposing new molecules capable of curatively combating malaria. The QSAR study was carried out using the Klopman-Peradejordi-Gómez (KPG) technique. This enabled us to express the logarithm of the median inhibitory concentration as a function of certain local atomic reactivity indices of certain atoms in the common skeleton of this series of 4-quinolinylhydrazone derivatives. Calculations were performed using the B3LYP hybrid functional of the DFT method in the 6-31G (d, p) extended basis implemented in the Gaussian program. Statistica 10 software was used to obtain the multiple linear regression equation. A statistically acceptable equation was obtained for the studied serie. Analysis of this equation led to the proposal of a 2D pharmacophore for anti-malarial activity. From this 2D pharmacophore we proposed hypothetical molecules and among these proposed compounds, four molecules showed good biological activity after log(IC₅₀) calculation.