Elucidating Antiangiogenic Potential of Rauwolfia serpentina: VEGFR-2 Targeting-Based Molecular Docking Study

Abstract

Angiogenesis plays a critical role in tumorigenesis as it provides the necessary blood supply to the newly grown solid tumor. It helps maintain the tumor microenvironment, promotes tumor development, progression, and metastasis. The vascular epithelial growth factor (VEGF), interacting with the tyrosine kinase receptor VEGFR-2 on endothelial cells, exerts its proangiogenic activity. Hence, targeting the VEGFR-2 signaling is considered a promising strategy to inhibit angiogenesis and thus cancer treatment. This study aims to identify the bioactive compounds derived from the medicinal herb Rauwolfia serpentina that effectively binds with VEGFR-2. The bioactive compounds of R. serpentina were first screened for their physicochemical properties using the DataWarrior program (version 5.5.0). Finally, 17 compounds that obeyed Lipinski’s rule of five and showed good drug-likeness were selected for molecular docking studies. Molecular docking results showed that the ligands ajmalicidine, 1, 2-dihydrovomilenine, rauwolscine, yohimbine, ajmaline, and papaverine interact strongly with the target VEGFR-2 receptor. Hydrogen bonds and hydrophobic interactions stabilized the interactions of these compounds with VEGFR-2. These compounds showed favourable drug-like properties and possess no significant toxicity. Therefore, the findings of this study indicate that the compounds derived from R. serpentina can be considered for the development of antiangiogenic drug candidates by targeting VEGFR-2.

Identification of Potential Poly (ADP-Ribose) Polymerase-1 Inhibitors Derived from Rauwolfia serpentina: Possible Implication in Cancer Therapy

“…These results support the possible anticancer potential of 1,2-dihydrovomilenine by targeting PARP-1. Similarly, a strong binding affinity of this compound with VEGFR-2 has recently been observed, indicating possible antiangiogenic activity [ 22 ].…”

“…The traditionally used medicinal herb R. serpentina has been reported to possess anticancer properties [ 27 ]. Previously, the potential antiangiogenic bioactive compounds of R. serpentina were identified by targeting VEGFR-2 using the molecular docking approach [ 22 ]. Molecular docking is a reliable technique used for in silico prediction of potential drug-like compounds for various diseases by targeting certain specific proteins [ 16 , 28 – 32 ].…”

“…Yohimbine is an antagonist of α 2-adrenergic receptor, which is reported to exhibit inhibitory activity against breast cancer and pancreatic cancer cell proliferation [ 39 – 41 ]. In our previous study, we observed a strong binding affinity of yohimbine against VEGFR-2 implicating its potential role in the inhibition of angiogenesis [ 22 ].…”

“…Rauwolscine was found to bind at the best pose to PARP-1 with a ΔG of −9.1 kcal/mol and a Ki of 212.64 nM, involving two hydrogen bonds via Gly888 and Met890, as well as additional significant and hydrophobic contacts through residues Trp861, His862, Gly863, Tyr889, Phe891, Tyr896, Ser804, Phe897, Ala898, Lys903, Tyr907, and Glu988 ( Figure 4 ). Like yohimbine, rauwolscine is also a known antagonist of α 2-adrenergic receptor with potential anticancer and antiangiogenic activity [ 22 ].…”

“…Using the AutoDock 4.2 program, the bioactive compounds of R. serpentina were docked against PARP-1 molecular target following the previously published procedure [ 22 , 23 ]. For this, the Lamarckian Genetic Algorithm was used, with the following parameters: a beginning population of 150 randomly inserted individuals, a maximum number of 2,500,000 energy assessments, a mutation rate of 0.02, and a crossover rate of 0.8.…”