Synthesis, Crystal Structure, Fluorescence Assay, Molecular Docking and QSAR/QSPR Studies of Temephos Derivatives as Human and Insect Cholinesterase Inhibitors

Abstract

In this study, Quantitative Structure‐Activity/property relationships (QSAR/QSPR) by means of multiple linear regressions (MLR) was performed to investigate the relationship between the 48 compounds of Temephos (Tem) drivatives and their bioactivities against acetylcholinesterase (AChE) of Tribolium castaneum. Two compounds Propylene‐N, N′‐bis (O, O′‐di Ethyl Phosphorothioat (12) and Ethylene N, ′N‐ di Methyl bis (O, O′‐ di Phenyl Phosphoramidate (24) had the most mortality on the T. castaneum. The compound 24 (IC50=34.54 ppm) is a good alternative to Tem. Also, QSAR calculations indicated that the electrostatic characteristics of the most effective insecticide are applied. In docking data, Tem derivatives with the backbone of P (O)‐NH−P(O), P(O)‐NH‐NH−P(O) and P(O)‐X−P(O) are located in the active site gorge of both AChE and butyrylcholinesterase (BChE) so as to maximize the favorable contacts. These compounds relate to enzymes by non‐covalent interactions such as hydrogen bonding, electrostatic and hydrophobic (as Trp82 and Trp286). Also, these cannot reach the end of the hole because of compounds are locked in the middle between the peripheral and acyl pocket site in AChE and BChE enzymes. The results of MLR and GA‐QSAR/QSPR model of human ChE showed that topological parameters affect the inhibitory potencies of the compounds on both of logK and p(IC50). logK and p(IC50) results have a good linear relationship.

Evaluating anti-coronavirus activity of some phosphoramides and their influencing inhibitory factors using molecular docking, DFT, QSAR, and NCI-RDG studies

“…Additionally, we have recently reporteed some of these compounds with both abilities to inhibits the acetylcholinesterase enzyme and low human toxicity. [31] , [32] , [33] Among the various phosphoramide derivatives [ 31 , [33] , [34] , [35] ], we have studied phosphoguanidines and phosphopyrazines as effective compounds in drug design because of their extensive biological properties [ 31 , 33 ]. Due to the fact that Phosphoramides are able to inhibit the main protease [36] , In this work we selected 35 phosphoramide compounds including the guanidine and pyrazine with the general formula (R 1 )(R 2 )P(X)–Y, that X=O or S, Y= creatine, amino pyrazine, amino benzimidazole, or amino pyrimidines, R 1 =(C 6 H 5 , OC 6 H 5 , OCH 3 , or OCH 2 CH 3 ), and R 2 =(R, Y) ( Figure 1 , Table 1 ).…”