Flavonoid and Phenolic Compounds from Carissa macrocarpa: Molecular Docking and Cytotoxicity Studies

Objective: The objective of the study is to investigate the phytochemical contents of the methanol extract of leaves of Carissa macrocarpa, the possible anticancer activities of the isolated compounds through molecular docking approaches as well as the potential cytotoxic activity. Materials and Methods: The methanol extract of the plant was subjected to several chromatographic procedures. In silico studies of the isolated compounds against four anticancer target kinases, namely, protein kinase B (PKB/AKT), phosphatidylinositol 3-kinase, protein kinase C, and rapidly accelerated fibrosarcoma kinase were performed. Potential cytotoxic activity of the isolated compounds was determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay against A549 cells. Results: Phytochemical investigation led to the isolation of three known flavonoid compounds: kaempferol 3-O-robinobioside (1), Kaempferol-3-O-α-L-rhamnopyranosyl (1-6)(4``-p-coumaroyl)β-D-galactopyranoside7-O-α-L-rhamnopyranoside (2), and variabiloside E (3) as well as three phenolic compounds: p-coumaric acid (4), salicin (5), and 3,4-dimethylphenol β-gentiobioside (6). In silico studies revealed that three out of the six compounds were strongly bound with one or more of the targets enzymes. Compound 3 showed broad-spectrum binding with the four targets with high docking score. Compounds 1–3 showed IC50comparable to that of positive control, doxorubicin. The rest of the compounds 4–6 showed relatively discrete IC50. Conclusion: The isolated compounds were reported for the first time from this plant. Compounds 1–3 could serve as lead compounds for development of new anticancer drugs.