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 P-31, C-13, H-1 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.