Anti-Cervical Cancer Study of a Labdane-type Diterpene Obtained from Legundi Fruit (Vitex triolia L.) Targeting the Bcl-2 Gene

Abstract

Abstract: The development and induction of cervical cancer carcinogenesis are linked to sexually transmitted Human Papillomavirus (HPV) infection, and can affect human genes, particularly those involved in the apoptotic process, one of which is the Bcl-2 gene. Several synthetic compounds, including pyrimidineylpiperazine, phenylpyrazole, kendomycin, and navitoclax, have been shown to be effective in inhibiting the antiapoptotic activity of Bcl-2, but it is the labdane-type diterpene content of the natural legundi fruit plant (Vitex trifolia L.) that has anticancer bioactivity, particularly in the process of genetic mutations, Apoptotic inhibition and therapeutic failure have yet to be discovered, particularly in cervical cancer. The study's goal was to investigate the mechanism of interaction (molecular docking) of labdane type-diterpene compounds with the antiapoptotic protein Bcl-2. In silico (docking molecular) research was used to determine the interaction between legundi fruit ligands and the Bcl-2 target protein in cervical cancer. The docking analysis results will then be visualized with the Discovery Studio 4.1, LigPlot+, and Ligand Scout 3.1 software. The interaction of proteins and ligands was studied to determine the number and type of bonds formed, such as hydrogen and hydrophobic bonds. The results were as follows: Gibbs energy -7.8, pKi 1.91 m, 10 hydrophobic bonds, and hydrophobic residues Leu80, Leu82, Thr83, Thr86, Ala87, Cys90, Met118, Glu121, Ser122, and Leu130. The findings presented here suggest that labdane-type diterpenes are powerful anticancer agents capable of inducing apoptosis and inhibiting the antiapoptotic action of the Bcl-2 gene, which should be investigated further in (pre)clinical studies.