Synthesis, design, biological activity, DFT study and molecular docking of new 1,2,4-triazine and 1,2,4-triazol derivatives bearing the phthalazine moiety

Abstract

The present work aims to synthesise a series of new compounds with a combination of 1,2,4-triazine and 1,2,4-triazole with a phthalazine components that have been created from compound (M4). The structural formula of these new compounds was confirmed by FT-IR, 1HNMR , 13CNMR and Mass spectra. Density functional theory (DFT) simulations utilising the Gausean-9 programme were used to rationalise the mechanism of all novel compounds. They demonstrations that the energy gap between compounds (M8–M10) is 0.09951 a.u., 0.108133 a.u. and 0.9857 a.u., respectively, between HOMO and LOMO. The molecular docking analysis unveiled the existence of several derivatives exhibiting significant binding affinities and unique interaction patterns with the target proteins. Derivatives M8–10 have been identified as the most favourable candidates, demonstrating the highest binding energies and a diverse range of interaction types, such as hydrogen bonding and pi interactions, across various distances. Derivative (M8–10) exhibits the highest binding energy at S = -8.15, -8.18, or -8.28 Kcal/mol with the 2VAM receptor and -8.52, -8.78 and -9.04 Kcal/mol with the 2G1H receptor. The analysis of the inhibition of the growth values in different concentrations against both Escherichia coli and Bacillus subtilis bacteria compared with amoxicillin. The presented research obviously demonstrates that compounds (M8–10) can serve as promising candidates for alternatives to new medications. The empirical findings were consistent with the anticipated outcomes derived from the molecular docking analysis.