Synthesis of some novel phthalazine-1,4-dione derivatives, DFT calculation, and biological activity

Phthalazine is an organic chemical formed by fusing pyridazine with a benzene ring. Because of the unique structure of phthalazine derivatives, such compounds have great potential for biological activities. We designed and synthesized thirty-two compounds phthalazine-1,4-dione derivatives. The compounds were intended to bind in the active site of the enzyme similarly to the reference AChE inhibitor donepezil. IR, 1H NMR, 13C NMR, and mass spectrometry were used to evaluate all of the target products. The biological activity tests on AChE and BChE were tested in vitro. The results of the first stage indicated that thirteen compounds exhibited greater than 50% inhibition of AChE and no activity in the prescribed range of 50% inhibition of BChE. As a result, no further experiments into BChE were conducted. Three of the targeted compounds have demonstrated exceptional activity and they are DEM-H-17, DEM-H-19, and DEM-H-22. Because the major portions of the compounds are comparable to donepezil, this explains why these compounds have high inhibitory activity against AChE. Molecular docking was used to assess the interactions of the active compounds with the active site residues of AChE. To evaluate how a biomolecular system would respond to a perturbation, molecular dynamic simulation was utilized. In each of these situations, numerous simulations of both the perturbed and unperturbed systems were run in order to discover consistent discrepancies in the outcomes. Furthermore, using density functional theory (DFT), the chemical reactivity characteristics of all targeted novel compounds were studied.