Synthesis, DFT investigation, molecular docking, drug-likeness and molecular dynamic analysis of new quinoxaline-based pyrazoline derivatives

Abstract

A variety of quinoxaline-based pyrazoline derivatives were prepared by Suzuki–Miyaura cross-coupling reaction. Optimization for Suzuki coupling reaction was caried out and the best obtained conditions were using Pd(PPh₃)₄ as a catalyst, K₂CO₃ as the base, and 1,4 dioxane as the solvent at 120 °C for 10 h. High yields of newly synthesized compounds, ranging from 59% to 82%, have been achieved. Spectroscopic analyses, including NMR, FT-IR, and mass spectrometric methods, characterized and identified the synthesized derivatives. The results of this study will affect future changes to the structure of quinoxaline, which includes adding a pyrazoline moiety, and the therapeutic potential of pyrazoline derivatives derived from quinoxaline. The density functional theory (DFT/B3LYP) approach and the double zeta plus polarization basis set 6–31 G (d,p) for the C, H, N, and O atoms were used to investigate the optimal molecular geometries of the selected derivatives . In the docking study, the best ligand (ligand f) was selected based on drug-likeness evaluation and ADMET analysis. The results demonstrated that this ligand exhibits efficacy comparable to the standard drug, achieving a docking score of -7.3 kcal/mol against the 2az5 target. Furthermore, molecular dynamics simulations were conducted to assess the stability the ligand f. The analysis revealed that ligand f shows enhanced stability, suggesting its potential as a promising oral drug candidate targeting 2az5. The findings presented here are crucial for future structural alterations to quinoxaline-based pyrazoline derivatives and the utilization of quinoxaline derivatives' therapeutic potential as anticancer or antimicrobial drugs.