Structure-based molecular screening and dynamic simulation of phytocompounds targeting VEGFR-2: a novel therapeutic approach for papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is the most prevalent type of thyroid cancer, with aggressive variants presenting major therapeutic challenges. Vascular endothelial growth factor receptor-2 (VEGFR-2) is a key regulator of tumor angiogenesis and is highly expressed in PTC, making it a promising target for therapeutic intervention. This highlights the potential of VEGFR-2 inhibition as an effective strategy for managing PTC. In this study, we employed virtual drug screening, molecular dynamics simulations, and binding free energy calculations to identify potential VEGFR-2 inhibitors from the African natural product database (AfroDb). Our virtual drug screening identified three lead compounds SA_0090, 17.3.1.7.8 and BMC_0005 with a docking scores of -9.04 kcal/mol, -8.96 kcal/mol, and -8.33 kcal/mol respectively, surpassing the control compound (-8.39 kcal/mol). Molecular dynamics simulation analysis confirmed the dynamic stability, structural compactness, and minimal residual fluctuations of the 17.3.1.7.8 and BMC_0005 compounds-VEGFR2 complexes. The binding free energy calculations further supported the strong interactions, with values recorded as -60.3861 ± 0.39 kcal/mol for the control, -52.2732 ± 0.37 kcal/mol for SA_0090, -52.7797 ± 0.62 kcal/mol for 17.3.1.7.8, and -61.476 ± 0.59 kcal/mol for BMC_0005. Additionally, the selected compounds exhibited highly favorable ADMET properties, including optimal water solubility, efficient gastrointestinal absorption, and a non-hepatotoxic profile, all aligning with Lipinski's rule of five. In conclusion, these findings highlight 17.3.1.7.8 and BMC_0005 compounds as compelling candidates for VEGFR-2 inhibition, offering a promising therapeutic avenue for papillary thyroid carcinoma, warranting further in vitro and in vivo validation for potential therapeutic use.