Toxic metabolites that could promote the formation of tumors are generated with high levels of β-glucuronidase activities. Hence, the inhibition of the β-glucuronidase enzyme is effective in the prevention of colonic carcinogenesis, and other diseases. This study aims to investigate the β-glucuronidase inhibitory effect of compounds that were isolated from Nauclea subdita (Korth.) Steud. and Alpinia pahangensis Ridley, together with their mode of inhibition, and their interactions with the enzyme. Angustine (1) and (E)-labda-8 (17),12-dien-15,16-dial (2) are secondary metabolites which were isolated from Nauclea subdita (Korth.) Steud. and Alpinia pahangensis Ridley, respectively. Both exhibited potent inhibitory activities against the β-glucuronidase enzyme with IC50 values of 5.6 ± 0.70 and 23.61 ± 3.32 μM, respectively. The enzyme kinetic studies suggested that compounds 1 and 2 were non-competitive inhibitors with inhibition constants (Ki) of 8.46 and 22.0 μM, respectively. In silico molecular docking and molecular dynamics simulation studies showed that the amino acid residues that interacted with compounds 1 and 2 were Phe161, Leu361, Phe448, Tyr468, Tyr472, and Leu561. These amino acid residues interacted with compound 1 with lower energy as compared to compound 2. Furthermore, the binding free energy of compound 1 (GBTOT value of −31.69 kcal mol−1) was found to be lower than that of compound 2 (GBTOT value of −22.32 kcal mol−1). Compound 1 was thus predicted to be a more active inhibitor through in silico molecular docking and molecular dynamics simulation studies.
- Molecular docking
- Molecular dynamics simulations