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

Leny Heliawati; Dikdik Kurnia; Eti Apriyanti; Putri Nabila Adinda Adrian Syah; Sun Theo Constan Lotebulo Ndruru

doi:10.2174/1386207326666230210141218

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

Comb Chem High Throughput Screen. 2023;26(13):2293-2303. doi: 10.2174/1386207326666230210141218.

Authors

Leny Heliawati¹, Dikdik Kurnia², Eti Apriyanti², Putri Nabila Adinda Adrian Syah³, Sun Theo Constan Lotebulo Ndruru⁴

Affiliations

¹ Department of Chemistry, Faculty of Mathematics and Natural Science, Universitas Pakuan, Bogor 16143, Indonesia.
² Department of Chemistry, Faculty of Mathematics and Natural Science, Universitas Padjadjaran, Sumedang 45363, Indonesia.
³ Department of Agricultural Technology, Faculty of Engineering, Universitas Pelita Bangsa, Bekasi 17530, Indonesia.
⁴ Research Center for Chemistry, Research Organization for Nanotechnology and Materials, National Research and Innovation Agency (BRIN), Kawasan PUSPIPTEK Area Serpong, Tangerang Selatan, Banten 15314, Indonesia.

PMID: 36809943
DOI: 10.2174/1386207326666230210141218

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.

Keywords: Corypha utan Lamk; FLT3; acute myeloid leukemia; anticancer agents; chromateography method; cycloartane triterpenoids.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis
Cell Line
Cell Line, Tumor
Leukemia, Myeloid, Acute* / drug therapy
Leukemia, Myeloid, Acute* / genetics
Mice
Mutation
Protein Kinase Inhibitors / pharmacology
Triterpenes* / pharmacology
fms-Like Tyrosine Kinase 3 / genetics

Substances

cycloartane
fms-Like Tyrosine Kinase 3
Protein Kinase Inhibitors
Triterpenes