ABSTRACT
Poly (ADP-ribose) polymerase-1 (PARP-1) has been recognized as a prospective target for the development of novel cancer therapeutics. Several PARP-1 inhibitors are currently being considered for anticancer drug development and clinical investigation. Lately, natural compounds seem to be excellent alternative drug candidates for cancer treatment. Rauwolfia serpentina is a medicinal plant traditionally used in Indian subcontinents to treat various diseases. This study has been designed to identify the bioactive compounds derived from R. serpentina for possible binding and inhibition of PARP-1 using the molecular docking approach. Thirteen compounds were found to interact with the target with a binding affinity greater than the value of -9.0 kcal/mol. After screening the physicochemical properties, only 5 ligands (ajmalicine, yohimbine, isorauhimbine, rauwolscine, and 1,2-dihydrovomilenine) were found to obey all the parameters of Lipinski's rule of five, showed maximum drug-likeness, and possess no significant toxicity. These ligands displayed strong interactions with target PARP-1 via several hydrogen bonds and hydrophobic interactions. Therefore, these identified compounds derived from R. serpentina can be considered for drug development against cancer-targeting PARP-1.
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.
