Hemisynthesis of Pentacyclic Triterpenoids from Diospyros foxworthyi with In vitro and In silico Anti-malarial Evaluation
Document Type
Article
Publication Date
1-1-2024
Abstract
A total of twelve pentacyclic triterpenoid derivatives based on betulin (1) and lupeol (2) scaffolds isolated from Diospyros foxworthyi were hemisynthesized by acylation or acetylation reactions with appropriate acid chloride or acetic anhydride. The structures of the hemisynthesised compounds were characterised by means of FT-IR, 1D- and 2D-NMR, as well as HRMS analysis. These compounds were assayed for in vitro anti-malarial studies by inhibition of beta-hematin formation assay with chloroquine as a positive control. Compounds 1d and 2f showed the strongest potential as beta-hematin formation inhibitors with IC50 values of 6.66 +/- 1.36 and 11.89 +/- 0.15 mu M, respectively, compared with the positive control (chloroquine; IC50 = 37.50 +/- 0.60 mu M). In silico molecular docking simulations were performed using AutoDock Vina for compounds 1d and 2f to investigate the binding interactions and free energy of binding (FEB) with the hemozoin supercell crystal structure (CCDC number: XETXUP01). The findings revealed several hydrophobic interaction modes between the 1d, 2f and hemozoin, with calculated FEBs of -8.4 +/- 0.2 and -8.9 +/- 0.0 kcal mol(-1), indicating strong and favourable interactions.
Keywords
Pentacyclic triterpenoids, hemisynthesis, anti-malaria, beta-hematin inhibition activity, molecular docking, Diospyros foxworthyi
Divisions
CHEMISTRY
Funders
Graduate Excellence Programme (GrEP) MARA
Publication Title
Current Organic Chemistry
Volume
28
Issue
10
Publisher
Bentham Science Publishers
Publisher Location
EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES