Designing, Spectral Confirmation, Hirshfeld Surface Analysis and Investigation of DNA Binding and Antibacterial Potentials as well as DFT, Molecular Docking and ADMET Evaluation of Hydrazide Based Schiff Bases

Two Schiff bases have been synthesized in three steps: first by reacting 2-(2,4-dichlorophenoxy)acetic acid with ethanol to give ethyl 2-(2,4-dichlorophenoxy)acetate, which was then treated with hydrazine to give 2-(2,4-dichlorophenoxy)acetohydrazide (a) in the 2nd step, and in the 3rd step, it was further reacted separately with salicylaldehyde and 4-(diethylamino)salicylaldehyde to give the final products (E)-2(2,4-dichlorophenoxy)-N-(2-hydroxybenzylidine)acetohydrazide (1) and (E)-2-(2,4-dichlorophenoxy)-N-(4-diethylamino)-2-hydroxybenzylidene)acetohydrazide (2). The products of each step were confirmed via instrumental techniques (FTIR, NMR and single crystal XRD). The crystal systems with space groups of a & 2 were triclinic & P-1 and monoclinic & P 21/n, respectively. The ADMET studies explored the potency of the screened compounds as drug. The compounds were tested for interaction with DNA using UV-Vis spectroscopy, viscosity measurement and molecular docking and results obtained from both studies suggest the intercalative mode of interaction. Both the compounds 1 & 2 have shown significant activity against the studied bacterial strains as compared to the standard drug Ciprofloxacin. The ADMET properties of compounds 1 & 2 were examined with the help of ADMETLab 3.0 to determine their drug-like characteristics. The drug-likeness and drug score of compounds 1 & 2 are 5.86 & 0.09 and 6.4 & 0.07, respectively. DFT study shows that the compounds have good chemical reactivity due to small energy gap value (ΔE). The red lines in the contour map are due to the presence of strong electron withdrawing oxygen atoms.

Aiman Siddique, Muhammad Sirajuddin, Ali Haider, Saqib Ali, Muhammad Nawaz Tahir, Moazzam Hussain Bhatti