Triterpene esters from Uncaria rhynchophylla hooks are able as new selective inhibitors on HIV-1 protease and their molecular docking study

Despite the remarkable advancements achieved with combination anti-retroviral agents (cART), the complete eradication of Human immunodeficiency virus (HIV) remains a formidable challenge due to various factors including adverse effects, adherence issues, and the emergence of viral resistance to existing therapies. Consequently, there is an urgent need for the development of safer and more effective drugs to combat modern resistant viral strains and advance acquired immunodeficiency syndrome (AIDS) therapeutics. Eight triterpene esters (1–8) were identified from Uncaria rhynchophylla hooks. These compounds exhibited selective inhibition of HIV-1 protease, with 3β-hydroxy-27-p-Z-coumaroyloxyurs-12-en-28-oic acid (8), showing the most potent inhibitory activity. Structure-activity relationship analysis highlighted the importance of an ursane moiety, a cis configuration, and a p-coumaroyloxy group for inhibitory activity. In silico docking results elucidate specific amino acid residues Asp29B, Lys45B, and Asn25A, interacting with the aromatic hydroxyl group at 7′, and carboxylic acid at 28. In addition, it interacts via π/anion and π/alkyl and alkyl hydrophobic interactions responsible for interactions and their mode of action. The study suggests that triterpene esters from U. rhynchophylla could represent a new class of selective HIV-1 protease inhibitors with less toxicity, suitable for combination antiretroviral therapy for AIDS.