Synthesis, X-ray crystallography, computational investigation on quinoxaline derivatives as potent against adenosine receptor A2AAR

Abstract

Quinoxaline represents one of the most important classes of heterocyclic compounds, which have exhibited a wide range of biological activities and industrial importance in many different fields. In this regard, we have synthetized two new quinoxaline derivatives. Their structures were confirmed by single-crystal X-ray analysis. The compounds show potent activity against adenosine receptors A2AAR based on structural activity relationship studies. Further molecular docking, molecular dynamics, ADMET analysis, and DFT (density functional theory) calculations were performed to understand the titled compound’s future drug candidacy. DFT computations confirmed the good stability of the synthesized compounds, as evidenced by the optimized molecular geometry, HOMO–LUMO energy gap, and intermolecular interactions. NBO analysis confirmed intermolecular interactions mediated by lone pair, bonding, and anti-bonding orbitals. All DFT findings were consistent with experimental results, indicating that the synthesized molecules are highly stable. These findings suggest that the synthesized compounds are promising candidates for further development as drugs for the treatment of A2AAR-related diseases.

Communicated by Ramaswamy H. Sarma

Keywords:

• Quinoxaline
• density functional theory
• NLO
• NBO analysis
• molecular docking and dynamics simulation
• ADMET

Acknowledgments

The authors extend their appreciation to the Researchers Supporting Project, King Saud University, Riyadh, Saudi Arabia, for funding this work through Grant No. RSP2024R353.

Disclosure statement

No potential conflict of interest was reported by the authors.

Scheme 1. Synthesis route 2 and 3.

Additional information

Funding

This research was funded by Researchers Supporting Project No. RSP2024R353, King Saud University, Riyadh, Saudi Arabia.