Molecular docking studies

Molecular docking simulations were performed using the software Autodock 4.2 Vina along with AutoDock Tools (ADT 1.5.6) using the hybrid Lamarckian Genetic Algorithm (LGA) as our previous studies³⁰. The three dimensional (3D) crystal structure of iNOS (PDB code: 3E7G) and COX-2 (PDB code: 1CX2) were obtained from the RCSB Protein Data Bank. The standard 3D structure (PDB format) of compounds 11 and 14 were constructed by using the “SKETCH” option function in SYBYL-X, whose configurations were determined by their NOESY spectra and TDDFT ECD calculations. The cubic grid box of 44 Å size (x, y, z) with a spacing of 0.375 Å and grid maps were built. The docking parameters consisted of setting the population size to 150, the number of evaluations to 2,500,000, the number of generations to 270,000, and the number of top individuals that automatically survive to 20, while the number of docking run was set to 40 with other default values during each docking run. The results of the most favorable free energy of binding were chosen as the resultant complex structures.