In silico evaluation of the potential anticancer effects of Viscosine and Quercetin 7-rutinoside: inhibition of DEAD-box RNA helicase DDX3X and b-cell lymphoma-extra large (Bcl-XL) activity

Abstract

Globally, cancer is the second leading cause of mortality, surpassed only by cardiovascular disorders. Among its various types, Non-Small Cell Lung Cancer (NSCLC) poses a significant global health risk. Chemotherapy is the most common therapeutic approach for treating cancer. However, chemotherapeutic drugs can cause serious toxicity by reducing the survival of both tumor and normal cells, thereby diminishing the survival chances of patients. Natural products extracted from medicinal plants serve as effective anticancer agents with minimal side effects. Among natural compounds, flavonoids have been reported as effective anticancer agents. In this study, two flavonoids, viscosine and quercetin 7-rutinoside, were evaluated for their antitumor potential using in silico models. These flavonoids were tested for their inhibitory activity against DEAD-box RNA helicase DDX3X (referred to as DDX3) and B-cell lymphoma-extra-large (Bcl-XL) enzymes through molecular docking and dynamic simulation analyses. The docking analysis revealed low docking scores and binding energies for both viscosine and quercetin 7-rutinoside. The overall docking results revealed that the selected flavonoids exhibited a favorable binding affinity for DDX3 and Bcl-X_L. They bind firmly to the key active sites and remain stably within the pocket regions of DDX3 and Bcl-X_L, thereby inhibiting their activity. This data was further supported by the RMSF and RMSD analyses. The preliminary molecular docking and simulation analyses confirm the promising inhibitory effects of viscosine and quercetin 7-rutinoside against DDX3 and Bcl-X_L. Therefore, these flavonoids could serve as potential antitumor drug candidates in the future. However, further experimental studies are needed to validate their potential for clinical trials.