In silico evaluation of potential antimalarial phytoconstituents from two medicinal plants used in Nigeria ethnomedicine

Abstract

Malaria has been a major public health burden, with over 249 million cases in 2022 accounting for millions of deaths annually in sub- Saharan Africa, especially among under five years children and pregnant women. It is however preventable and curable, but the  development of resistance to current medications leading to loss of effectiveness has been a major concern to clinicians in managing  malaria. Hence, there is an urgent need to develop new antimalarial candidates. This study uses an in-silico approach to explore the  inhibitory potential of bioactive compounds in Piper guineense and Chrysobalanus icaco, used traditionally in treating malaria and  related diseases, against plasmepsin II (PDB ID:1LF3), a drug target protein of Plasmodium falciparum. Structures of phytoconstituents in  these plants characterised with GC-MS were obtained from the PubChem database in their 3D format. The target protein was obtained  from the Protein Data Bank (PDB) and prepared using Biovia Discovery Studio 2020. Molecular docking was done using PyRx  software, and post-docking analysis was visualised using Biovia Discovery Studio 2020. ADMET profiling and toxicity testing were done  with SwissADME and ProTox-3.0 web servers. The docking study results revealed that 7 ligands from P. guineense have binding affinity  scores ranging from -7.0 to -7.5 kcal/mol compared to DHA (-7.4 kcal/mole). Steviol has the highest binding free energies of -7.5 kcal/mol  in the plant. Moreover, 13 ligands from C. icaco exhibited binding affinities between -7.5 and -9.1 kcal/mol, which were above that of the  positive control agent, DHA (-7.4 kcal/mol). Spiro[androst-5-ene-17,1'-cyclobutan]-2'-one,3-hydroxy-, (3beta,17beta)- showed the highest  binding free energy of -9.1 kcal/mol in C. icaco. Other compounds from Piper guineense: Epiglobulol, (-)-alphaCopaene, Agarospirol,  4,6,6-Trimethyl-2-(3-methylbuta-1,3-dienyl)-3-oxatricyclo [5.1.0.0(2,4)] octane, and Bulnesol had similar amino acids interaction as the  positive control, Dihydroartemisinin (DHA). None of the 38 ligands investigated failed the Lipinski rule of 5 and possesses favourable  ADMET parameters. Some of the compounds presented promising in silico bioactivities for antimalarial drug development. Further  analytical study can, therefore, be done to isolate candidate molecules to develop new antimalarial leads.