Quinoxaline as Dual Modulators of Apoptotic Regulators Bcl-2 and Bax: A Combined In Vitro and In Silico Anticancer Approach

Meshak Dhanashekaran, Cecileya Jasmin; Venugopal, Vinod Prabhu; Chokkalingam, Nivetha; Sakthivel, Kunnathur Murugesan; Narayanaswamy, Radhakrishnan

doi:10.31557/APJCP.2026.27.3.1017

Quinoxaline as Dual Modulators of Apoptotic Regulators Bcl-2 and Bax: A Combined In Vitro and In Silico Anticancer Approach

Document Type : Research Articles

Authors

¹ Department of Biochemistry, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences (Deemed to be University), Thandalam, Chennai, Tamil Nadu, India.

² Department of Microbiology, School of Sciences, P P Savani University, Dhamdod, Kosamba, Surat, Gujarat, India.

³ Department of Biochemistry, Bharath Institute of Higher Education and Research (BIHER) Chennai, Tamil Nadu, India.

⁴ Department of Biochemistry, PSG College of Arts & Science, Coimbatore, Tamil Nadu, India.

10.31557/APJCP.2026.27.3.1017

Abstract

Objective: This study aimed to evaluate the antioxidant potential of quinoxaline and investigate its molecular interactions with cancer-related proteins through computational docking. Methods: Antioxidant activity of quinoxaline was assessed using DPPH, FRAP, ABTS, hydrogen peroxide, superoxide, and reducing power assays at varying concentrations, and IC₅₀ values were calculated. Molecular docking studies were performed to examine the interactions of quinoxaline with cancer-associated proteins, including epidermal growth factor receptor (EGFR), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and β-actin. Results: Antioxidant assays showed a concentration-dependent increase in inhibitory activity, with IC₅₀ values of 130.446 µM (DPPH), 151.343 µM (FRAP), 171.551 µM (ABTS), 108.194 µM (H₂O₂), 104.592 µM (superoxide), and 95.893 µM (reducing power assay). Molecular docking analysis revealed that quinoxaline exhibited strong binding affinity with the anti-apoptotic Bcl-2, suggesting potential inhibition of its function. Additionally, favorable interactions with the pro-apoptotic Bax were observed, indicating a possible dual mechanism of apoptosis induction. Conclusion: Quinoxaline demonstrated significant antioxidant activity and potential pro-apoptotic effects by targeting key apoptotic regulators. The docking results suggest that quinoxaline could inhibit anti-apoptotic Bcl-2 while promoting the activity of the pro-apoptotic Bax, thereby inducing apoptosis and highlighting its potential as a promising anticancer agent.

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