Phosphorhydrazides as urease and acetylcholinesterase inhibitors: biological evaluation and QSAR study

New phosphorhydrazide compounds (1–7, 13, 15–16) and thiophosphorhydrazide (14 and 17) were synthesized and characterized by 31P, 13C, 1H NMR and IR spectroscopy. Furthermore, the crystal structure of compound (C6H5NH)(C6H5O)P(O)(NH–NH2) (2) was investigated. The activities of derivatives on acetylcholinesterase (AChE) and urease were determined. Quantitative structure–activity relationship (QSAR) was used to understand the relationship between molecular structural features and inhibitory. DFT–QSAR models for enzymes demonstrated the importance of E LUMO parameter in describing the anti-AChE and anti-urease activities of the synthesized compounds. The correlation matrix of QSAR models and docking analysis confirmed that electrophilicity descriptor can control the influence of the polarizability properties of N–H functional group of PAH derivatives in the inhibition of enzymes.