Molecular Design of N-Salicyloyl Tryptamine Derivatives Via Quantitative Structure-Property Relationship )QSPR( and Molecular Dynamic Simulation Methods

Abstract

N-salicyloyl tryptamine derivatives as anti-neuroinflammatory agents have a potent strategy to cure neuroinflammatory diseases including Alzheimer and Parkinson. Computational methods of quantitative structure properties relationships (QSPR) and molecular dynamics were successfully used to design of four novel N-salicyloyl tryptamine with improved properties. The QSPR model of five variables was presented to predict anti- neuroinflammatory activity of N-salicyloyl tryptamine derivatives. The quantum descriptors as Hartree Fock energy, ionization energy, softness, dipole moment and the thermal energy, were calculated with density functional theory at the B3LYP/6-311G level. Cross validation of multivariate linear regression (MLR) was used to build and evaluate the model QSPR. The model possesses coefficients of the highest squared correlation coefficient (R²) of 0.900 for the training set and 0.817 for the test set. The statistical results exhibited high internal and external consistency as demonstrated by the validation methods. Three of designed compounds showed good pharmacokinetic properties by QSPR predictions. These results provided strong guidance for the discovery and design of novel potential anti- neuroinflammatory compounds. Also, the adsorption of the designed compounds on functionalized carbon nanotube (8, 0) was investigated using molecular dynamics simulation with COMPASS force field. Results indicated that the adsorption of designed N-salicyloyl tryptamine derivatives on f-CNT involves a partial π–π interaction and hydrogen bonding. The study of investigation the interactions of N-salicyloyl tryptamine with f-CNT (8, 0) can be useful for finding the main CNT-based carriers for these derrivatives.