Molecular Docking Studies of Glycyrrhetinic Acid Derivatives as Anti-Colorectal Cancer Agents

In this study, the anti-CRC activities of 40 glycyrrhetinic acid derivatives were proposed and evaluated by the molecular docking method, which allowed the flexibility of both ligand-receptor, with twelve CRC-related targets. The proposed derivatives, which clearly distinguish isomers at position 18 as well as the different tautomers, were divided into five groups including (1) glycyrrhetinic acid and its oxidation derivatives, (2) glycoside derivatives, (3) 3β-amine derivatives, (4) five-membered heterocyclic ring-combined derivatives, and (5) six-membered heterocyclic ring-combined derivatives. Finally, we selected four out of twelve proposed targets related to CRC with good binding affinities to the proposed glycyrrhetinic acid derivatives including Epidermal Growth Factor Receptor (EGFR), Focal Adhesion Kinase (FAK), Lactate Dehydrogenase A (LDHA), and Thymidylate Synthase (TS). From there, we also gained 9/40 derivatives for EGFR (pKd ≥ 9); 10/40 derivatives for FAK (pKd ≥ 10); 9/40 derivatives for LDHA (pKd ≥ 10), and 6/40 derivatives for TS (pKd ≥ 9). The glycoside derivatives showed the best binding affinity (especially the glucuronide derivative 5b), followed by the 3β-amino derivatives (especially the 3β-(phenylamino) derivative 8b) and the five-membered heterocyclic ring-combined derivatives (especially the pyrrole derivative 10a or pyrazole derivative 11.2a), while the six-membered heterocyclic ring-combined derivatives had less potential to inhibit selected targets.