In Silico Evaluation of Nitrogen-Containing Tetrahydropyridine and Piperidine Metabolites Identified from Strobilanthes tonkinensis Lindau Leaves as Potential Antibacterial Agents
DOI:
https://doi.org/10.24114/ijcst.v9i2.68983Keywords:
Strobilanthes tonkinensis, molecular docking, tetrahydropyridine, piperidine, ADMET, antibacterial agentsAbstract
Strobilanthes tonkinensis Lindau (daun paris), a Southeast Asian aromatic herb, contains several nitrogen-containing piperidine and tetrahydropyridine (THP) metabolites identified by prior GC-MS profiling but not previously evaluated in silico. This study assessed the molecular docking interactions of four such metabolites, 2-propionyl-3,4,5,6-tetrahydropyridine (2-PTHP), 2-acetyl-3,4,5,6-tetrahydropyridine (2-ATHP), 2-(2-furyl)piperidine (2-FP), and 1-(piperidin-2-yl)propan-1-one (PPO) against two bacterial protein targets, FtsA (PDB: 3WT0) and DNA gyrase subunit B (GyrB; PDB: 6KZV), using AutoDock Vina, complemented by ADMET prediction via SwissADME and ProTox 3.0. All four compounds showed moderate binding affinities against FtsA (−5.7 to −5.9 kcal/mol) and GyrB (−5.2 to −6.0 kcal/mol), substantially weaker than the native co-crystallized ligands (−11.5 and −8.9 kcal/mol, respectively). 2-FP exhibited the strongest GyrB affinity (−6.0 kcal/mol) and partially reproduced the native ligand's catalytic-residue contacts (ASP73, ASN46), whereas PPO showed the most catalytically relevant FtsA interaction profile, engaging SER13, VAL211, and ASP210. Structure-activity comparison identified the presence of a piperidine NH (hydrogen bond donor) versus an imine nitrogen as the principal determinant of polar-contact capacity within this scaffold. All compounds fully satisfied Lipinski's Rule of Five, showed high predicted gastrointestinal absorption and blood-brain barrier permeability, and were classified as GHS Acute Oral Toxicity Class IV with inactive predicted hepatotoxicity and carcinogenicity. These findings constitute preliminary computational evidence supporting 2-FP and PPO as candidates for further in vitro antibacterial validation..
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