Title:Natural Cycloartane Triterpenoids from Corypha utan Lamk. with Anticancer
Activity towards P388 Cell Lines and their Predicted Interaction
with FLT3
Volume: 26
Issue: 13
Author(s): Leny Heliawati*, Dikdik Kurnia, Eti Apriyanti, Putri Nabila Adinda Adrian Syah and Sun Theo Constan Lotebulo Ndruru
Affiliation:
- Department of Chemistry, Faculty of Mathematics and Natural Science, Universitas Pakuan, Bogor 16143, Indonesia
Keywords:
Corypha utan Lamk., cycloartane triterpenoids, acute myeloid leukemia, FLT3, chromateography method, anticancer agents.
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.