Drug design of new therapeutic agents: molecular docking, molecular dynamics simulation, DFT and POM analyses of new Schiff base ligands and impact of substituents on bioactivity of their potential antifungal pharmacophore site.

Since Schiff base derivatives have a wide range of biological activities, novel Schiff base derivatives were designed and synthesized in satisfactory yields. H NMR, C NMR, IR, mass and elemental analysis were used to provide a complete structural characterization of the new synthesized Schiff bases (). The antiproliferative activity properties of compounds were tested against two human cancer cell lines including breast (MDA-MB-231) and colon (DLD-1). The compounds overall did not show high cytotoxic activity against both cancer cell lines compared to the positive control drug cisplatin. The synthesized Schiff base compounds were further screened for their antimicrobial activities against five bacterial strains ( (ATTC 25922), (ATTC 14028), (ATCC 25923), (ATCC 6633), (ATCC 11778)) and two fungal strains ( (ATCC 10231) and (ATCC 90030)) using broth micro dilution techniques. The mode of action for the antimicrobial effect in the experimental part was explored through molecular docking. The stability of target-ligand complexes obtained from the docking were assessed through molecular dynamics simulation. The binding affinity of the compounds toward the target protein were also investigated using MMPBSA. Furthermore, electrochemical properties of some compounds was analyzed by DFT calculations. By using POM theory, it becomes more easy to control the bioactivity of drugs. Here, how the physicochemical properties play a crucial role in the orientation of their bioactivity was demonstrated.Communicated by Ramaswamy H. Sarma.