Betulinic and ursolic acids from Nauclea latifolia roots mediate their antimalarial activities through docking with PfEMP-1 and PfPKG proteins.

BACKGROUND: Chemotherapies target the PfEMP-1 and PfPKG proteins in Plasmodium falciparum, the parasite that causes malaria, in an effort to prevent the disease's high fatality rate. This work identified the phytochemical components of Nauclea latifolia roots and docked the chemical compounds against target proteins, and examined the in vivo antiplasmodial effect of the roots on Plasmodium berghei-infected mice. METHODS: Standard protocols were followed for the collection of the plant's roots, cleaning, and drying of the roots, extraction and fraction preparation, assessment of the in vivo antiplasmodial activity, retrieval of the PfEMP-1 and PfPKG proteins, GCMS, ADME, and docking studies, chromatographic techniques were employed to separate the residual fraction's components, and the Swis-ADME program made it possible to estimate the drug's likeness and pharmacokinetic properties. The Auto Dock Vina 4.2 tool was utilized for molecular docking analysis. RESULTS: The residual fraction showed the best therapeutic response when compared favorably to amodiaquine (80.5%) and artesunate (85.1%). It also considerably reduced the number of parasites, with the % growth inhibition of the parasite at 42.8% (D2) and 83.4% (D5). Following purification, 25 compounds were isolated and characterized with GCMS. Based on their low molecular weights, non-permeation of the blood-brain barrier, non-inhibition of metabolizing enzymes, and non-violation of Lipinski's criteria, betulinic and ursolic acids were superior to chloroquine as the best phytochemicals. Hence, they are lead compounds. CONCLUSION: In addition to identifying the bioactive compounds, ADME, and docking data of the lead compounds as candidates for rational drug design processes as observed against Plasmodium falciparum target proteins (PfEMP-1 and PfPKG), which are implicated in the pathogenesis of malaria, the study has validated that the residual fraction of N. latifolia roots has the best antiplasmodial therapeutic index.

Evaluation of Annona muricata extract against Staphylococcus aureus isolate and in-silico activity of bioactive compounds against Capsular protein (Cap5O).

BACKGROUND: Staphylococcus aureus has prevailed against the majority of antibiotics currently in clinical use, making it a significant global public health problem. As a safer alternative, bioactive compounds have been explored. Annona muricata has been shown to possess antimicrobial activity. However, there are few reports on the molecular activity of A. muricata bioactive compounds against S. aureus. Thus, this study was aimed at evaluating the antimicrobial activity of its crude extract as well as investigating the potential of its bioactive compounds against the Cap5O capsular polysaccharides (CPS) of S. aureus via molecular docking. METHODS: Collection of plant leaves, preparation of extracts, anti-nutrient analysis, phytochemical screening via crude method and gas chromatography-mass spectrophotometer (GC-MS), isolation and characterization of S. aureus and the antimicrobial activity test were all done using standard protocols. Molecular docking was done using the MCULE online tool with emphasis on docking scores, toxicity, and other properties. RESULTS: Crude screening of the extracts showed the presence of polyphenols, hydroxyanthraquinones, reducing compounds, flavonoids, saponins, glycosides, alkaloids, anthraquinones, phlobatannins and tannins in different concentrations. Anti-nutrient analysis showed the presence of allowable levels of evaluated anti-nutrients. GC-MS revealed a total of twenty-nine (29) bioactive compounds, out of which only 4 (13.80%) docked without toxicity and these were bicyclo[4.1.0]heptan-2-one 6-methyl, trichloromethane, carbonic acid 2-dimethylaminoethyl propyl ester, and 1-methyl-4-phenyl-5-thioxo-1,2,4-triazolidin-3-one on either the NAD-binding or C-terminal substrate binding domain of Cap5O. CONCLUSION: Results obtained show that Cap5O could be a potential drug target for multi-drug resistant S. aureus, however, further studies aimed at evaluating these bioactive compounds individually and in combination are highly needed.