Structural and molecular modelling studies of antimelanogenic piper-amide TRPM1 antagonists

ABSTRACT

Piper-amides exhibit diverse biological activities, including antimelanogenic effects. In our previous studies, we identified a potent piper-amide derivative that inhibited melanogenesis via the TRPM1 calcium channel. Despite its potential as a therapeutic target, the three-dimensional structure of TRPM1 is still not available. Thus, structure-guided compound design and the discovery of novel inhibitors of melanogenesis have been limited. In the present study, a series of computational methods, including homology modelling, docking, molecular dynamics simulation and field-based pharmacophore modelling, were integrated to explore the structural features of natural piper-amide-like compounds related to the TRPM1 target. These studies suggested the binding mode and provided a 3D pharmacophore model of the ligands, which can be helpful in understanding the TRPM1–ligand interactions at the molecular level and in designing potent antagonists of TRPM1.

KEYWORDS:

• piper-amide
• TRPM1
• homology modelling
• docking
• molecular dynamics simulation
• field-based pharmacophore modelling

Disclosure statement

No potential conflict of interest was reported by the authors.

Supplemental Material

Supplementary material for this article can be accessed at: https://doi.org/10.1080/1062936X.2019.1574894

Additional information

Funding

This work was supported by the Mid-Career Researcher Program [NRF-2016R1A2A1A05005375] of the National Research Foundation (NRF) grant funded by the Korea government (MSIP).