Albendazole repurposing on VEGFR-2 for possible anticancer application: In-silico analysis

Drug repurposing is the finding new activity of the existing drug. Recently, Albendazole's well-known antihelmintic has got the attention of an anticancer drug. Plausible evidence of the interaction of Albendazole with one of the types of tyrosine kinase protein receptor, vascular endothelial growth factor receptor-2 (VEGFR-2) is still not well understood. Inhibition of the VEGFR-2 receptor can prevent tumor growth. The current study investigated the interaction of Albendazole with VEGFR-2.It was found that the said interaction exhibited potent binding energy Delta G = -7.12 kcal/mol, inhibitory concentration (Ki) = 6.04 mu M, and as positive control comparison with standard drug (42Q1170A) showed Delta G = -12.35 kcal/mol and Ki = 881 mu M. The key residue Asp1046 was formed involved hydrogen bonding with Albendazole. The molecular dynamics simulation study revealed the stable trajectory of the VEGFR-2 receptor with Albendazole bound complex having significant high free energy of binding as calculated from Molecular Mechanics Generalized Born and Surface Area study Delta G = -42.07 +/- 2.4 kcal/mol. The binding energy is significantly high for greater stability of the complex. Principal component analysis of molecular docking trajectories exhibited ordered motion at higher modes, implying a high degree of VEGFR-2 and Albendazole complex stability as seen with the standard drug 42Q. Therefore, the current work suggests the role of Albendazole as a potent angiogenesis inhibitor as ascertained by its potential interaction with VEGFR-2. The findings of research will aid in the future development of Albendazole in anticancer therapy.

Automated summary

Drug repurposing is the process of discovering new activity for existing drugs. This study investigates the interaction of Albendazole, a well-known antihelmintic drug, with the tyrosine kinase protein receptor VEGFR-2. The findings suggest that Albendazole has potential as a potent angiogenesis inhibitor and could aid in the development of anticancer therapies.