Phytochemical Repurposing of Natural Molecule: Sabinene for Identification of Novel Therapeutic Benefits Using In Silico and In Vitro Approaches.

Repurposing of drugs/natural or synthetic chemicals is a promising approach to identify the new therapeutic indication/use and mode of action. In pharmaceuticals, this process is used to save the time and cost for the drug discovery process with reduced risk of failure. In the present studies, repurposing of a natural molecule: sabinene (major phytochemical in cardamom) was used to characterize the new biological activities using in silico as well as in vitro approaches. In silico similarity searching demonstrated that (+)-3-carene possessed the maximum structural similarity with sabinene. In vitro activities of (+)-3-carene were repurposed for sabinene based on similarity hypothesis (similar structures may have similar biological activities). In vitro studies demonstrated that sabinene is having antimicrobial activity and also showed concentration-dependent antioxidant activity by 2,2-diphenyl-1-picrylhydrazyl scavenging assay. Sabinene treatment protected the yeast cells from hydrogen peroxide-induced cytotoxicity in 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide assay. Moreover, it was found that sabinene treatment decreased the generation of oxidative stress and also decreased the activities of antioxidant enzymes; glutathione S-transferase, catalase, and lipid peroxidase as compared with untreated yeast cells. Sabinene was also found to have angiostatic and antiangiogenic effects. These results were supported by molecular docking studies against antiangiogenic targets. Therefore, the results of these studies suggested that structurally similar molecules are having the same activity. The phytochemical repurposing using in silico similarity searching as well as in vitro approaches can also be applied for other phytochemicals whose activities are not/less known. Furthermore, this could also be useful in the novel lead/scaffold discovery and target fishing.