Hemisynthesis of Pentacyclic Triterpenoids from Diospyros foxworthyi with In vitro and In silico Anti-malarial Evaluation

Title:Hemisynthesis of Pentacyclic Triterpenoids from Diospyros foxworthyi with In vitro and In silico Anti-malarial Evaluation

Volume: 28 Issue: 10

Author(s): Muhammad Solehin Abd Ghani, Nur Ain Latifhaa Abu Bakar, Arba Pramundita Ramadani, Arde Toga Nugraha, Khalijah Binti Awang, Mohammad Tasyriq Che Omar, Unang Supratman, Ezatul Ezleen Kamarulzaman and Mohamad Nurul Azmi Mohamad Taib*

Affiliation:

• Natural Products and Synthesis Organic Laboratory (NPSOLab), School of Chemical Sciences, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia

Keywords: Pentacyclic triterpenoids, hemisynthesis, anti-malaria, β-hematin inhibition activity, molecular docking, Diospyros foxworthyi.

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 β-hematin formation assay with chloroquine as a positive control. Compounds 1d and 2f showed the strongest potential as β-hematin formation inhibitors with IC₅₀ values of 6.66 ± 1.36 and 11.89 ± 0.15 μM, respectively, compared with the positive control (chloroquine; IC₅₀ = 37.50 ± 0.60 μM). 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.

Cite this article as:

Abd Ghani Solehin Muhammad, Abu Bakar Ain Latifhaa Nur, Ramadani Pramundita Arba, Nugraha Toga Arde, Awang Binti Khalijah, Che Omar Tasyriq Mohammad, Supratman Unang, Kamarulzaman Ezleen Ezatul and Mohamad Taib Nurul Azmi Mohamad*, Hemisynthesis of Pentacyclic Triterpenoids from Diospyros foxworthyi with In vitro and In silico Anti-malarial Evaluation, Current Organic Chemistry 2024; 28 (10) . https://dx.doi.org/10.2174/0113852728294047240315063815