Aims: To identify natural inhibitors against MCT8 for Allan-Herndon-Dudley Syndrome.
Background: Monocarboxylate Transporter 8 (MCT8) is a Thyroid Hormone (TH) transporter
which is highly expressed in the liver and brain. Mutations in the MCT8 gene (SLC16A2) cause a
syndrome of psychomotor retardation in humans, known as Allan–Herndon–Dudley syndrome
(AHDS). Currently, no treatment is available for AHDS. Therefore, there is a need to discover
new inhibitors of MCT8 for treating AHDS.
Objective: Considering the importance of natural compounds in drug discovery, this study aimed
to identify potential natural inhibitors against MCT8.
Methods: As Protein-ligand interactions play a key role in structure based drug design, this study
screened 24 natural kinase inhibitors and investigated their binding affinity against MCT8 by using
molecular docking. The modelled 3D structure of MCT8 docked with 24 compounds using PyRX
through Autodock Vina. Drug-likeness studies were made using Swiss ADME and Lipinski’s rule of
five was performed. Triac, desipramine and silychristin were used as the positive controls. Binding
energies of the selected compounds were compared with that of positive controls.
Result: The results showed that emodin exhibited best binding energy of −8.6 kcal/mol followed
by helenaquinol, cercosporamide and resveratrol. Moreover, it was observed that emodin and helenaquinol
exhibit higher binding energy than the positive controls. Cercosporamide and resveratrol
exhibited higher binding energy than triac and desipramine and showed the binding energy
similar to silychristin.
Conclusion: This study reveals that these compounds could be promising candidates for further
evaluation for AHDS prevention.