Secondary Metabolites Isolation of Cryptocarya massoy and In Silico Study of its Anticancer Potency a Tasya Citra Violeta, b Reza Aditama, a Dikhi Firmansyah, c Wahyu Hidayat and a Lia Dewi Juliawaty*
a Organic Chemistry Division, Faculty of Mathematics and Natural Sciences, Institut Teknologi Bandung, Jalan Ganesha no. 10, Bandung
b Biochemistry Division, Faculty of Mathematics and Natural Sciences, Institut Teknologi Bandung, Jalan Ganesha no. 10, Bandung
c Department of Forestry Faculty of Agriculture University of Lampung, Jl. Prof. Soemantri Brojonegoro No. 1 Gedung Meneng, Bandar Lampung
Abstract
The MAPK signaling cascade is one of the most frequently mutated and deregulated signaling pathways in leukemia cancer. MEK1 and ERK2 have been widely used as targets for inhibitor development, such as trametinib and ulixertinib. However, using those inhibitors may result in side effects such as coughing up blood to the point of causing prolonged bleeding from cuts. Therefore, alternative natural compound inhibitors are still to be made available. The Cryptocarya genus is one of the Indonesian plants reported to have significant anticancer properties, including against the murine leukemia P-388 cell line. Until now, research on the potential of Indonesian Cryptocarya secondary metabolites as MEK1 and ERK2 inhibitors has been limited. This research aimed to isolate secondary metabolites from the stem bark of C. massoy and study the potential of secondary metabolites from the stem bark of C. massoy as MEK1 and ERK2 inhibitors. The isolation of secondary metabolites from C. massoy was carried out in several steps, i.e., maceration of the stem bark powder with acetone solvent and separation of the acetone extract using chromatography methods, including vacuum liquid chromatography (VLC) and gravity column chromatography (GCC), to obtain pure compounds. The structure of the isolated compounds was determined using 1D NMR (1H-NMR and 13C-NMR). The results of the research indicated the presence of two compounds, namely (-)-syringaresinol, first discovered in the stem bark of C. massoy, but previously obtained from the wood of C. massoy, and also C-10 massoilactone, the main compound from C. massoy. The molecular docking analysis revealed that C-10 massoilactone from C. massoy had potency as MEK1 inhibitors with a docking score of -5,9 kcal/mol. In contrast, (-)-syringaresinol from C. massoy had the potency as ERK2 inhibitors with a docking score of -8,2 kcal/mol. Hydrophobic interactions were found to be important in the MEK1 and ERK2 inhibition mechanisms.
Keywords: Cryptocarya massoy, MEK1, ERK2, anticancer, in silico, isolation
