In Silico Analysis of Pandan Leaves (Pandanus amaryllifolius) as Potential Alpha-1-Adrenergic Receptor Agonists for Hypotension Therapy Rahadian Zainul(a*), Iffat Syafiqoh Afif (b), Faiqa Haura Tsagifa (c)
(a) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Negeri Padang, Air Tawar Barat 25132, Padang, Indonesia.
Center for Advanced Material Processing, Artificial Intelligence, and Biophysics Informatics (CAMPBIOTICS), Universitas Negeri Padang, Air Tawar Barat 25132, Padang, Indonesia.
INTI International University, Negeri Sembilan, 71800, Malaysia.
Email: *rahadianzmsiphd[at]fmipa.unp.ac.id
Orcid: 0000-0002-3740-3597
(b) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Padang State University, Padang, Indonesia
Orcid: 0009-0000-7800-0260
(c) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Padang State University, Padang, Indonesia.
Orcid: 0009-0009-3448-502X
Abstract
Hypotension is characterized by systolic blood pressure below 90 mmHg and diastolic blood pressure below 60 mmHg. This condition significantly increases the risk of falls, syncope, and cardiovascular complications, particularly among the elderly. While pharmacological interventions such as midodrine are effective, they are frequently associated with adverse side effects, necessitating the exploration of safer natural alternatives. This study evaluated the potential of bioactive alkaloids from Pandan leaves (Pandanus amaryllifolius) as antihypotensive agents through an in silico molecular docking approach. Ten bioactive compounds were screened against the alpha-1-adrenergic receptor (PDB ID: 7B6W) using midodrine as a reference ligand. The results demonstrated that three lead compounds, specifically pandamarilactonines A, pandamarilactone 32, and pandanusine B, exhibited superior binding affinities compared to midodrine, with docking scores reaching -7.4760 kcal/mol. Molecular interaction analysis revealed stable hydrogen and ionic bonding with key residues such as GLU199 and TRP184. Furthermore, drug-likeness and ADMET evaluations confirmed that these candidates adhere to Lipinski and Veber rules, showing high intestinal absorption rates between 77% and 99% with no predicted hepatotoxicity. These findings provide a compelling scientific basis for the development of pandan-derived alkaloids as high-efficacy herbal therapies for hypotension with a potentially lower risk of side effects. Although these computational results are promising, further in vitro and in vivo studies are essential to validate their clinical bioactivity and safety.
Keywords: Pandanus amaryllifolius, hypotension, molecular docking, alpha-1-adrenergic receptor, in silico
