A series of 23 novel phosphorhydrazide derivatives were synthesized and characterized by spectral techniques, and their anti-ChE, antibacterial and insecticide activities were investigated.

step of organic nitrogen mineralization to produce ammonia and carbamate. The carbamate produced during this reaction spontaneously decomposes, at physiological pH, to give a second molecule of ammonia and bicarbonate [3][4][5][6]. The hydrolysis of the reaction products causes an abrupt overall pH increase, the major cause for the negative side effects of the action of urease both for human and animal health, and for agriculture. Urease inhibitors have also been proposed to control urea hydrolysis in soil [6][7][8][9][10][11][12][13][14][15][16]. In particular, compound with the P(X)-NH2 segment (X = O, S) have received considerable attention as urease inhibitors. The most effective inhibitors are substituted both thiophosphinicamide and phosphinicamide families. Many phosphoramide compounds are the most effective compounds currently available to retard the hydrolysis of urea fertilizer in soil and to decrease ammonia volatilization and nitrite accumulation in soils treated with urea. (Thio)phosphoramide inhibited urease by forming a chelated complex with the nickel ion in the active site of enzyme. Phosphoramide acts as urease inhibitors by coordinating itself to the nickel ions of active site [15]. The oxygen or sulfur atoms and amide group of the inhibitor molecule are engaged in the formation of a bridge between the Ni(1) and Ni(2) ions. In this work, we have compared the effectiveness of new (thio) phosphorhydrazide compounds (1-17) to inhibit jack bean urease toward (thio)phosphoramides. In addition, we carried out quantitative structure-activity relationship (QSAR) studies on the aforementioned derivatives to gain an understanding of the activity shown by such compounds, to propose its union mode to the urease active site, and to try to create the correlation between the electronic and structural parameters in contrast to the inhibition potency.Abstract New phosphorhydrazide compounds (1-7, 13, 15-16) and thiophosphorhydrazide (14 and 17) were synthesized and characterized by 31 P, 13 C, 1 H NMR and IR spectroscopy. Furthermore, the crystal structure of compound (C 6 H 5 NH)(C 6 H 5 O)P(O)(NH-NH 2 ) (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 antiAChE 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.

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