LAUSR

Abstract In this study, two novel compounds possessing both acridine and sulfonamide scaffolds were designed by molecular hybridization. These compounds were achieved via condensation of dimedone, 2,3-dichlorobenzaldehyde and sulfadiazine (5SD)/sulfathiazole (5ST) in the presence of a catalytic amount of p-toluenesulfonic acid. The obtained hybrid compounds were characterized by IR, 1H-NMR, 13C-NMR and mass spectra. Additionally, the proposed structure of 5SD was proved by single crystal X-ray analysis. Antibacterial activity of the molecules was evaluated against three Gram-positive and two Gram-negative microorganisms using four reference compounds including sulfadiazine and sulfathiazole. Computational analysis on the basis of density functional theory (DFT) calculations, molecular dynamics (MD) simulations and molecular docking have revealed the most important information about the reactive properties of the newly synthesized molecules. DFT calculations have been used in order to identify the molecular sites prone to electrostatic interactions and electrophilic attacks. The same theoretical approach was also used for the identification of the molecular sites possibly sensitive towards the autoxidation mechanism. MD simulations were employed for the determination of the molecular sites prone to interact with water. Finally, molecular docking procedure against dihydropteroate synthase has been used in order to predict the most plausible binding modes and support the experimental data.