Molecular docking, MD Simulation, Synthesis, DFT, and Biological Evaluations of Newer Generation Imidazolo-Triazole Hydroxamic Acid linked with Para nitro Phenyl group

Based on the structural features of vorinostat, a new set of imidazolo-triazole hydroxamic acid derivatives were designed (F۱-F۴). Then all the designed molecules were molecular docked against HDAC ۲ receptor. F۴ showed maximum binding energy of -۸.۷ kcal/mol and standard vornostat showed -۷.۲ kcal/mol. All the designed molecules were simulated using Gromacs software to calculate RMSD, RMSF, and other MD simulation data. All simulation data showed good interaction between ligand and receptor. Then all the molecules were synthesized by three parts: synthesis of para nitrophenyl linked triazolo hydroxamic acid, and oxazolone derivative. In a separate flask, substituted oxazolone derivatives were synthesized from aromatic aldehyde. In the final step, substituted oxazolone and para nitrophenyl linked triazolo hydroxamic acid were reacted to produce final set of molecules (F۱-F۴). DFT analyses were also performed to identify the most reactive molecule and F۴ emerged as most chemically reactive molecule with good electrophilicity. Furthermore, in vitro antiproliferative activity against breast cancer cell line showed that F۴ was the most effective anticancer molecule among all the synthesized molecules.

کلیدواژه ها:

Hydroxamic acid ، Molecular docking ، MD simulation ، MMPBSA ، Synthesis ، DFT