Synthesis of Novel Spiro Pyrano-Phenazine-Quinoxaline Derivatives Via a One-Pot and Five-Component Reaction As Potential Anticancer Agents by Molecular Modeling Calculation Publisher

Summary: Can hybrid molecules block a cancer-driving enzyme? Docking studies highlighted compound 5j as a promising EGFR binder, pending biological tests. #DrugDiscovery #Oncology

Mahdavinia G H ; Mardaneh P ; Mirzazadeh M ; Lavian S
Source: ChemistrySelect Published:2026

Abstract

Globally, cancer ranks as the second most common cause of human mortality in modern times. In spite of significant advancements in early detection and treatment, cancer remains a formidable challenge. Crucial functions in diverse physiological mechanisms are often overexpressed in a wide range of cancer types are mediated by tyrosine kinase receptor activity. Observations reveal that pharmacophores that contain quinoxaline, chromene, and phenazine exhibit a variety of therapeutic properties. Furthermore, computational evaluations have highlighted the significance of incorporating quinoxaline, chromene, or phenazine into the molecular structure to enhance the compound's ability to engage with the active site of the EGFR enzyme. Therefore, our study aimed to design and synthesize hybrid derivatives of quinoxaline, chromene, and phenazine that can potently suppress EGFR activity through selective binding to its active site. We employed the MCR method due to its short reaction time, minimal labor, and cost-effectiveness, as well as its ability to improve molecular complexity and diversity. Additionally, in silico evaluations, including molecular docking studies, DFT analysis, and ADMET index assessments, were performed on the synthesized compounds. Findings from the molecular docking analyses revealed that among the formed complexes within EGFR, compound 5j was the most stable compared to other analogs. © 2026 Wiley-VCH GmbH.