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. 1H NMR, 13C NMR, IR, mass and elemental analysis were used to provide a complete structural characterization of the new synthesized Schiff bases (3-6). 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 in vitro antimicrobial activities against five bacterial strains (Escherichia coli (ATTC 25922), Salmonella thyphimurium (ATTC 14028), Staphylococcus aureus (ATCC 25923), Bacillus subtilis (ATCC 6633), Bacillus cereus (ATCC 11778)) and two fungal strains (Candida albicans (ATCC 10231) and Candida glabrata (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.

Could pyrimidine derivative be effective against Omicron of SARS-CoV-2?

BACKGROUND: A pyrimidine based Schiff base was examined in this report. Structural and spectral characterizations were done with Gaussian software. Active sites of the compound were determined using molecular electrostatic potential (MEP) maps. AIM: We focused to determine whether pyrimidine based Schiff base would be an inhibitor against Omicron of SARS-CoV-2 in silico. RESULTS AND CONCLUSION: As one of the perils the world has seen lately, omicron of SARS-CoV-2, is a complication to be solved. For the sake of that, anti-viral properties of studied pyrimidine based Schiff base compound were investigated with molecular docking calculations. It was found that the quantitative values of the calculated parameters were in the applicable ranges. In accordance with these results, it will be an important guide for future in vitro and in vivo analysis (Tab. 3, Fig. 7, Ref. 70).