Molecular docking and ADMET profiling of xanthones from Securidaca longepedunculata targeting oxidative stress in hypertension

Abstract

Hypertension remains a major global health challenge, with oxidative stress playing a pivotal role in its pathogenesis and complications. In this study, six naturally-occurring xanthones isolated from Securidaca longepedunculata roots were evaluated for their dual-action potential against hypertension via molecular docking with Cu-Zn superoxide dismutase (SOD, PDB: 2C9V), angiotensin-converting enzyme (ACE, PDB: 5AMB) and the L-type calcium channel (Cav1.1, PDB: 6JP5). All xanthones exhibited strong binding affinities to SOD (docking scores: − 8.0 to − 7.3 kcal/mol), demonstrating potential for enzyme interaction, though with lower scores than the reference compound quercetin (− 9.0 kcal/mol) which is known to modulate SOD activity. 2D interaction analyses revealed that xanthones engage SOD through hydrogen bonds and π-alkyl/π-sulfur interactions with key residues, showing binding modes which are sharing some similarities with quercetin’s interaction pattern. All xanthones showed higher affinity to ACE with docking scores between − 8.3 and − 7.4 kcal/mol compared to captopril (− 5.7 kcal/mol). Several xanthones also demonstrated high binding to Cav1.1, comparable to or exceeding nifedipine. ADMET profiling predicted favorable oral bioavailability and low toxicity for all compounds. These computational results provide a molecular rationale for the traditional antihypertensive use of S. longepedunculata and highlight its xanthones as promising dual-action scaffolds for further experimental drug development.