# Molecular Targets of Minor Cannabinoids in Breast Cancer: In Silico and In Vitro Studies
## 2 Results
### Molecular Docking Results
\begin{table}
\begin{tabular}{c c c c} \hline \hline
**Cannabinoid Name** & **Cannabinoid Class** & **Binding Affinity—Aromatase** & **Binding Affinity—ER\(\alpha\)** \\  & & **(kcal/mol)** & **(kcak/mol)** \\ \hline
8-Oxo-(-)-\(\Delta^{9}\)_-trans_-tetrahydrocannabinol & \(\Delta^{9}\)-THC & \(-9.2\) & \(-7.8\) \\ \hline
11-Acetoxy-(-)-\(\Delta^{9}\)_-trans_-tetrahydrocannabinolic acid A & \(\Delta^{9}\)-THC & \(-8.3\) & \(-7.8\) \\ \hline (-)-\(\Delta^{9}\)_-trans_-tetrahydrocannabinolic acid A-C\({}_{4}\) & \(\Delta^{9}\)-THC & \(-6.7\) & \(-5.4\) \\ \hline (-)-\(\Delta^{9}\)_-trans_-Hydrocannabinol & \(\Delta^{9}\)-THC & \(-3.8\) & \(-6.5\) \\ \hline Cannabidiol (CBD) & Cannabidiol & \(-8.7\) & \(-7.3\) \\ \hline (-)-Cannabidivarin (CBDV) & Cannabidiol & \(-7.6\) & \(-7.6\) \\ \hline Cannabidiol monoomethylether (CBDM) & Cannabidiol & \(-7.3\) & \(-7.4\) \\ \hline Cannabidiol-C\({}_{4}\) (CBDB) & Cannabidiol & \(-6.9\) & \(-7.8\) \\ \hline Cannabidiolic acid (CBDA) & Cannabidiol & \(-5.7\) & \(-8.3\) \\ \hline Cannabinerolic acid & Cannabigerol & \(-6.7\) & \(-7.7\) \\ \hline Camagerol & Cannabigerol & \(-6.6\) & \(-6.0\) \\ (-)-6,7-cis-Epoxycannabigerolic acid & Cannabigerol & \(-6.3\) & \(-6.9\) \\ \hline Cannabigerovalic acid (CBGVA) & Cannabigerol & \(-6.1\) & \(-6.9\) \\ \hline (-)-6,7-trans_-Epoxycannabigerol & Cannabigerol & \(-5.8\) & \(-6.3\) \\ \hline
5-Acetyl-4-hydroxy-cannabigerol & Cannabigerol & \(-5.4\) & \(-6.9\) \\ \hline Cannabielesoin acid A & Cannabielesoin & \(-5.1\) & \(-7.0\) \\ \hline Cannabielesoin acid B & Cannabielesoin & \(-5.9\) & \(-5.2\) \\ \hline Cannabieylcol & Cannabicyclol & \(-9.8\) & \(-8.9\) \\ \hline Cannabicyclovarin & Cannabicyclol & \(-9.3\) & \(-7.8\) \\ \hline Cannabicyclic acid & Cannabicyclo & \(-5.5\) & \(-8.7\) \\ \hline Cannabichromevarin & Cannabichromene & \(-7.1\) & \(-7.6\) \\ \hline Cannabichromeic acid (CBCA) & Cannabichromene & \(-6.4\) & \(-7.7\) \\ \hline Cannabichromene (CBC) & Cannabichromene & \(-6.0\) & \(-7.0\) \\ (-)-7-Hydroxycannabichromene & Cannabichromene & \(-5.5\) & \(-8.5\) \\ \hline Cannabichromevarinic acid & Cannabichromene & \(-5.2\) & \(-7.6\) \\ \hline
8-Hydroxycannabinol & Cannabinol & \(-7.9\) & \(-6.0\) \\ \hline Cannabinol (CBN) & Cannabinol & \(-5.9\) & \(-8.9\) \\ \hline
8-Hydroxycannabinolic acid A & Cannabinol & \(-4.8\) & \(-5.4\) \\ (-)_trans_-Cannabitrol-OEt-C\({}_{3}\)* & Cannabitriol & \(-3.5\) & \(-7.5\) \\ \hline (-)-A2-trans_-(1R,3R,6R)-isotetrahydrocannabinol-C\({}_{5}\) & Miscellaneous & \(-9.8\) & \(-6.6\) \\ \hline Cannabinvorone & Miscellaneous & \(-8.4\) & \(-7.2\) \\ \hline Cannabichromanone C & Miscellaneous & \(-7.8\) & \(-6.7\) \\ \hline Dehydrocannabifuran & Miscellaneous & \(-7.3\) & \(-8.5\) \\ \hline Cannabichromanone B & Miscellaneous & \(-7.0\) & \(-6.4\) \\ \hline (-)-(7R)-Cannabicournarononic acid & Miscellaneous & \(-6.5\) & \(-6.4\) \\ \hline Cannabicoumaronome-C\({}_{5}\) & Miscellaneous & \(-6.0\) & \(-7.2\) \\ \hline Cannabichromanone-C\({}_{3}\) & Miscellaneous & \(-5.4\) & \(-7.5\) \\ \hline \hline \end{tabular}
* Et = ethyl.  
\end{table} 
Table 3: Phytocannabinoids presenting dual functions: AI and ER\(\alpha\) antagonist profiles. Information about the binding affinity score of the 36 cannabinoids on aromatase and ER\(\alpha\) is presented. The information regarding **CBG** and **CBN** is also presented. The binding of these compounds to ER\(\alpha\) is depicted in Figure 4. **CBD** (Figure 4) was also included for molecular docking comparison, as it acts as an ER antagonist with inverse agonist properties [44]. As target flexibility is important for the ligand/ER\(\alpha\) binding, and in order to better understand the energetic stability and conformational pattern of the ligand/target complexes, a 10 ns MD simulation was performed based on the most stable complex structures derived from the docking studies presented in Figure 4. After the MD run, all the ligands remained in the active site in locations similar to the ones presented at the beginning of the simulation (Supplementary Figure S4).