Natural Cycloartane Triterpenoids from Corypha utan Lamk. with Anticancer Activity towards P388 Cell Lines and their Predicted Interaction with FLT3

Abstract

Background: Cancer is the second leading cause of death in the world. Leukemia is a type of cancer that accounts for 31.5% of all cancers in children under the age of 15 in industrialized countries and 15.7% in developing countries. The inhibition of FMS-like tyrosine kinase 3 (FLT3) is a suitable approach for acute myeloid leukemia (AML) therapy as it is overexpressed in AML. Aim and Objective: This study intends to explore the natural constituents from the bark of Corypha utan Lamk., and assess their cytotoxicity on murine leukemia cell lines (P388) in addition to predicting their interaction with FLT3 as a studied target by computational methods. Methods: Compounds 1 and 2 were isolated from Corypha utan Lamk using the stepwise radial chromatography method. These compounds were assessed for their cytotoxicity against Artemia salina using the BSLT and P388 cells and the MTT assay. The docking simulation was employed to predict the possible interaction between triterpenoid and FLT3. Results: Isolation from the bark of C. utan Lamk. generated two triterpenoids, cycloartanol (1) and cycloartanone (2). Based on the in vitro and in silico studies, both compounds were found to have anticancer activity. The evaluation of cytotoxicity from this study reveals that cycloartanol (1) and cycloartanone (2) could inhibit P388 cell growth (IC50 value at 102.6 and 110.0 μg/mL, respectively). The binding energy of cycloartanone was -9.94 Kcal/mol with a Ki value of 0.051 μM, while the binding energy and Ki value of cycloartanol (1) were found to be 8.76 Kcal/mol and 0.38 μM, respectively. These compounds also demonstrate a stable interaction by forming hydrogen bonds with FLT3. Conclusion: Cycloartanol (1) and cycloartanone (2) exhibit potency as anticancer agents by inhibiting P388 cells in vitro and the FLT3 gene in silico.