Targeting Dopamine Transporter (DAT) with Peronema canescens Bioactives: A Molecular Docking Study for Stroke-Related Pain and Sedation Management

Rizki Rachmad Saputra (Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Palangka Raya, Palangka Raya, 73112, Indonesia)
Rifaldi Lutfi Fahmi (Department of Food Technology, Institute of Chemistry and Biotechnology, Tallinn University of Technology, Ehitajate tee 5, 19086, Tallinn, Estonia)
Eka Novitasari (Department Applied Chemistry, Graduate School of Life Sciences, Ritsumeikan University, Shiga, 525-8577, Japan)
Luluil Maknun (Applied Chemistry Laboratory, Nugen Bioscience Indonesia, Jakarta, 15138, Indonesia)
Jeddah Yanti (Department of Geography, Faculty of Mathematics and Natural Sciences, Universitas Negeri Makassar, Makassar, 90222, Indonesia)
Raiyan Fairozi (Sehat Bersama Clinic, Faculty of Health Sciences, Universitas Teuku Umar, Meulaboh, 23615, Indonesia)

Helium: Journal of Science and Applied Chemistry
Vol. 5 No. 1 (2025): Helium: Journal of Science and Applied Chemistry

Pain and drowsiness are common symptoms of stroke recovery, which can be difficult to manage owing to neurochemical abnormalities in the dopamine system. The Dopamine Transporter (DAT) controls dopamine levels, which influences pain perception and neurological recovery. This study examines bioactive chemicals found in Peronema canescens leaves and their possible interactions with DAT. AutoDock Vina was used to perform molecular docking simulations to determine the binding affinities of Peronemin derivatives (A2, A3, and B2) to the Dopamine Transporter (DAT). The receptor structure (PDB ID: 4M48) was created by eliminating water molecules, introducing polar hydrogens, and optimizing the structure using AutoDockTools. Ligand structures were translated to the proper format, and docking was conducted using a grid box centered on DAT's active site, with an exhaustiveness value of 10. The Peronemin derivatives A2, A3, and B2 demonstrated binding affinities stronger than nortriptyline, native ligand (−10.6, −10.5, and −10.3 kcal/mol, respectively) and binding similarities ranging from 72.2% to 94.4%. These findings suggest that Peronema canescens bioactives may be promising candidates for stroke-related pain and sedative control, warranting further experimental validation.