In Silico Study of Dysotriflorin Compounds from Majegau Stem Bark (Dysoxylum densiflorum) as a Potential Antihypertensive Agent

Hypertension is a non-communicable disease with high prevalence in Indonesia and a major risk factor for cardiovascular disorders. The Renin-Angiotensin-Aldosterone System (RAAS) plays a crucial role in its pathophysiology through activation of Angiotensin-Converting Enzyme (ACE) and Angiotensin II type 1 receptor (AT1R). This study investigates the potential of dysotriflorin A–M, triterpenoid metabolites from the bark of majegau (Dysoxylum densiflorum), as antihypertensive candidates using an in-silico approach. The methods included preparation of ACE and AT1R proteins, optimization of the compound’s 3D structures, and molecular docking simulations with AutoDock Vina. Interaction analysis assessed binding affinity, bond types, and amino acid residues, complemented by toxicity prediction (ProTox) and bioavailability evaluation (Lipinski’s rule). Results showed dysotriflorin A–M had binding affinities ranging from –8.5 to –9.4 kcal/mol for ACE and –8.1 to –9.0 kcal/mol for AT1R, outperforming captopril (–7.4 kcal/mol) and losartan (–8.1 kcal/mol). Hydrogen and hydrophobic interactions supported complex stability. Toxicity prediction indicated LD50 of 2000 mg/kg (class IV, relatively safe), while bioavailability met 4 of 5 Lipinski parameters. In conclusion, dysotriflorin A–M demonstrates promising potential as a natural antihypertensive candidate with favorable safety and bioavailability, warranting further in-vitro and in-vivo validation.