Rapid Dereplication of Trunk Bark Constituents of Croton sylvaticus and Molecular Docking of Terpenoids from Three Congolese Croton Species

TL;DR

This paper identifies new terpenoids in Croton sylvaticus and evaluates their potential as anticancer compounds through molecular docking.

Contribution

The study reports the first isolation of three terpenoids in C. sylvaticus and evaluates their anticancer potential using molecular docking.

Findings

Acetyl aleuritolic acid, caryophyllene oxide, and phytol were isolated for the first time in C. sylvaticus.

Molecular docking showed strong binding affinities to cancer-related receptors HAR and HIF-1α.

The compounds exhibited favorable drug-like properties according to ADMET analysis.

Abstract

Phytochemical investigation and bioactivity evaluation of terpenoids from the Croton species were conducted. The chemical composition of C. sylvaticus was explored using chemical phytochemical screening techniques and dereplication of 13C NMR data using MixONat software (v. 1.0.1). Natural products with diverse structural features were identified in the dichloromethane extract of trunk bark. These include monoterpenoids, sesquiterpenoids, diterpenoids, triterpenoids, along with other minor metabolites, such as steroids, saponins, and fatty acids. Further purification of this extract led to the isolation of three major secondary metabolites, acetyl aleuritolic acid, caryophyllene oxide, and phytol. These secondary metabolites were reported for the first time in C. sylvaticus. The isolated compounds were structurally compared to known anticancer terpenoids previously identified in two other Congolese Croton species. Through molecular docking studies, the predicted binding affinities of the identified compounds were assessed, and possible structure–activity relationships (SAR) were proposed. Two structurally characterized receptors—the human androgen receptor (HAR, PDB ID: 1E3G) and hypoxia-inducible factor 1-alpha (HIF-1α, PDB ID: 3KCX), known for their involvement in cancer-related pathways, were used for molecular docking investigations. Among the tested compounds, 1, 2, 3, and 12 were identified as having strong-to-moderate predicted binding affinities to both protein targets, along with favorable drug-like properties according to the ADMET analysis. This investigation could justify the use of Croton plants in traditional medicine. In addition, our study highlights the potential of the Congolese Croton species as sources of bioactive secondary metabolites.

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