Determination of the Content of Isoquinoline Alkaloids in Selected Plant Extracts and Study of Their Cholinesterase-Inhibiting Activity and Cytotoxicity Against Human Melanoma Cells Using In Vitro and In Silico Methods

Different plants containing isoquinoline alkaloids are known to exhibit various biological activities such as anti-inflammatory, antimicrobial, antiviral, antioxidant, antihyperglycemic, cholesterol-lowering, antifungal and anticancer behaviors. Diseases that pose a significant health burden include neurodegenerative diseases and cancer. Current treatments for these diseases are still inadequate, so new therapeutic agents are needed to treat them more effectively. The aim of this study was to determine the content of selected isoquinoline alkaloids in plant extracts obtained from the leaves of Peumus boldus Molina (Monimi aceae); the rhizomes of Coptis chinensis Franch. (Ranunculaceae); the roots of Jateorhiza palmate (Lam.) Miers (Menispermaceae); the herbs of Eschscholzia californica Cham. (Papaveraceae); and the bark, buds, and flowers of Magnolia officinalis Rehder & E.H.Wilson (Magnoliaceae). The aim of the study was also to determine, in vitro and in silico, the acetylcholinesterase and butyrylcholinesterase inhibitory activity of the investigated isoquinoline alkaloids and the plant extracts containing them. The investigated alkaloid standards and most of the investigated plant extracts exhibited significant anti-cholinesterase activity. Extracts obtained from the rhizomes of Coptis chinensis exhibited the highest activity against acetylcholinesterase and butyrylcholinesterase, with IC50 = 4.85 and 9.58 µg/mL, respectively. The kinetic results indicated that boldine, noncompetitively; coptisine, competitively; and columbamine, in mixed mode, inhibited acetylcholinesterase activity. The activity of butyrylcholinesterase was inhibited by coptisine and columbamine in mixed mode. The next objective of our research was to determine the cytotoxic activity of the tested plant extracts against human melanoma A375 and SK-MEL-3 cell lines. The highest cytotoxicity was observed for the extract obtained from the rhizomes of Coptis chinensis, with IC50 = 4.06 and 27.3 µg/mL against A375 and SK-MEL-3 cells, respectively. All investigated plant extracts exhibited a selectivity index of cytotoxic activity greater than 1.0 against human melanoma cancer cells and fibroblasts, which indicates their selective cytotoxicity towards cancer compared to normal cells. An especially high selectivity index (17.27) was obtained for the Coptis chinensis rhizome extract. Particularly interesting results were obtained for the Coptis chinensis rhizome extract due to its high inhibitory activity against cholinesterases and significant cytotoxicity towards human melanoma cells, combined with a more than seventeen-fold lower toxicity towards fibroblasts; consequently, Coptis chinensis may be particularly recommended for further research.