# Molecular Targets of Minor Cannabinoids in Breast Cancer: In Silico and In Vitro Studies
## 2 Results
### Molecular Docking Results

Table 1: _Cont._Regarding ER\(\alpha\), we analyzed the docking positions and the energy scores and selected 85 compounds of the 129 cannabinoids as the best candidates to act as ER\(\alpha\) antagonists (Table 2, Supplementary Figure S2). The cannabinoids selected belong mainly to **A9-THC**, **CBG**, **CBC**, and miscellaneous classes and all of them bind in the vicinity of the residues Val534, Leu525, Glu353, Arg394, Phe404, Met421, His524, and Asp351, being mainly stabilized by hydrophobic interactions. The cannabinoid with the best binding affinity was cannabioexpane, which presented a value of \(-9.2\) kcal/mol. \begin{table}
\begin{tabular}{c c c c} \hline \hline \multirow{2}{*}{**Cannabinoid Name**} & **Cannabinoid Class** & \begin{tabular}{c} **Binding Affinity (kcal/mol)** \\ \end{tabular}  & **Relevant Interactions** \\ \hline (-)-\(\Delta^{9}\)_-trans_-Tetrahydrocannabihexol & \(\Delta^{9}\)-THC & \(-8.5\) & \begin{tabular}{c} Close to Asp351; hydrophobic interactions \\ with Trp383 \\ \end{tabular}  \\ \hline \(\alpha\)-Terperyl (-)-\(\Delta^{9}\)_-trans_-tetrahydrocannabinolate & \(\Delta^{9}\)-THC & \(-8.0\) & \begin{tabular}{c} Close to Asp351; hydrophobic interactions \\ with Phe404 \\ \end{tabular}  \\ \hline \(11\)-Acetoxy-(-)-\(\Delta^{9}\)_-trans_-tetrahydrocannabinolic acid A & \(\Delta^{9}\)-THC & \(-7.8\) & \begin{tabular}{c} Hydrogen bonds with Glu353 and Arg394; close to Asp351; hydrophobic interactions with Phe404 \\ \end{tabular}  \\ \hline \(8\)-oxo-(-)-\(\Delta^{9}\)_-trans_-tetrahydrocannabinol & \(\Delta^{9}\)-THC & \(-7.8\) & \begin{tabular}{c} Close to Asp351; hydrophobic interactions \\ with Trp383 \\ \end{tabular}  \\ \hline (-)-\(\Delta^{9}\)_-trans_-tetrahydrocannabinol & \(\Delta^{9}\)-THC & \(-7.8\) & \begin{tabular}{c} Close to Asp351; hydrophobic interactions \\ with Trp383 \\ \end{tabular}  \\ \hline \(4\)-Terpenyl & \(\Delta^{9}\)-_trans_-tetrahydrocannabinolate & \(\Delta^{9}\)-THC & \(-7.3\) & \begin{tabular}{c} Hydrogen bond with Asp351; hydrophobic interactions \\ interactions with Trp383 \\ \end{tabular}  \\ \hline \(\Delta^{9}\)-Tetrahydrocannabinol (THC) & \(\Delta^{9}\)-THC & \(-7.1\) & \begin{tabular}{c} Close to Asp351; hydrophobic interactions \\ with Trp383 \\ \end{tabular}  \\ \hline (-)-\(\Delta^{9}\)_-trans_-tetrahydrocannabinol-C\({}_{4}\) & \(\Delta^{9}\)-THC & \(-7.0\) & \begin{tabular}{c} Close to Asp351; hydrophobic interactions \\ with Trp383 \\ \end{tabular}  \\ \hline (-)-\(\Delta^{9}\)_-trans_-tetrahydrocannabinol & \(\Delta^{9}\)-THC & \(-6.5\) & \begin{tabular}{c} Hydrogen bond with Asp351; hydrophobic interactions with Trp383 \\ \end{tabular}  \\ \hline (-)-\(\Delta^{9}\)_-trans_-tetrahydrocannabinolic acid A-C\({}_{4}\) & \(\Delta^{9}\)-THC & \(-5.4\) & \begin{tabular}{c} Hydrogen bonds with Val534 and Asp351; hydrophobic interactions with Trp383 \\ \end{tabular}  \\ \hline (-)-\(\Delta^{8}\)_-trans_-tetrahydrocannabinol & \(\Delta^{8}\)-THC & \(-8.4\) & \begin{tabular}{c} Close to Asp351; hydrophobic interactions \\ with Trp383 \\ \end{tabular}  \\ \hline \(10\)-Hydroxy-\(\Delta^{8}\)-tetrahydrocannabinol & \(\Delta^{8}\)-THC & \(-8.1\) & \ \begin{tabular}{c} Hydrogen bond with Glu353; close to Asp351; hydrophobic interactions \\ hydrophobic interactions with Trp383 \\ \end{tabular}  \\ \hline \(10\)-Hydroxy-\(\Delta^{8}\)-tetrahydrocannabinol & \(\Delta^{8}\)-THC & \(-7.4\) & \begin{tabular}{c} Close to Asp351; hydrophobic interactions \\ with Trp383 \\ \end{tabular}  \\ \hline \(10\)-\(\alpha\)-Hydroxy-\(\alpha\)oxo-\(\Delta^{8}\)-tetrahydrocannabinol & \(\Delta^{8}\)-THC & \(-6. \begin{table}
\begin{tabular}{c c c c} \hline \hline
**Cannabinoid Name** & **Cannabinoid Class** & \begin{tabular}{c} **Binding** \\ **Affinity (kcal/mol)** \\ \end{tabular}  & **Relevant Interactions** \\ \hline Cannabidihexol & Cannabidiol & \(-6.8\) & \begin{tabular}{c} Close to Asp351; hydrophobic interactions \\ with Trp383 \\ \end{tabular}  \\ \hline Cannabigerol & Cannabigerol & \(-6.9\) &