Synthesis, spectroscopic characterization, DFT and molecular dynamics of quinoline-based peptoids

Peptoids mimic the functions of peptides which have a side chain appended to amidic nitrogen instead of α carbon. This structural change in their backbone gives them increased resistance from proteolysis, improved biostability, greater immunogenicity, and better bioavailability. Therefore, they are specifically designed for various biological activities, including antibacterial, antifungal, antioxidant, antifouling, and anticancer properties. The aim of the research is the one-pot synthesis of quinoline-based peptoids 5(a-b) via Ugi-4CR by the reaction of 1R-(-)-myrtenal 1, benzylamine 2, quinoline-based carboxylic acids 3(a-b), and cyclohexyl isocyanide 4. These peptoids were characterized by FT-IR, 1H NMR, 13C NMR, and HR ESI-MS. In computational studies, the spectral results of 5(a-b) were compared with the calculated spectral values computed at B3LYP/6-311G (d,p) level. TD-DFT method was used to predict electron excitation of 5(a-b) and the contribution of orbitals. The electronic transition of peptoids from charge distribution was computed using natural bond order (NBO) analysis. NPA and MEP analysis was calculated to predict charge distribution in 5(a-b). The FMOs analysis was executed to calculate the global reactivity descriptor to predict the reactivity and stability of peptoids. DFT analysis showed that 5b was slightly more reactive than 5a due to extended conjugation. The biological activities were also predicted using an in silico approach that involved molecular docking and molecular dynamic (MD) simulations. The antiulcer, antibacterial, and antifungal activities were predicted based on ligand–protein binding interactions, binding energy calculations, and dissociation constants. 5(a-b) were evaluated in-vitro for anticholinesterase activity, and they showed 71% inhibition. The umbrella sampling was performed to probe ligand–protein binding.