Encephalartos ferox is cycad belonging to the Zamiaceae family. It is endemic in northern Kwazulu-Natal, South Africa. 12 The plant parts, especially the leaves are used as prophylaxis in the treatment of oestrogen-dependent tumour and diabetes. 13 However, there are limited studies reporting on the medicinal properties of its fruit. Our previous study investigated the chemical composition of the E. ferox methanolic fruit extract. The gas chromatography mass spectrophotometry chromatogram profile revealed a total of eight volatile compounds namely cis-Vaccenic acid (1), 9-Octadecenoic acid, 1,2,3-propanetriyl ester (2), 4H-Pyran-4-one, 2,3-dihydro-3,5-dihydroxy (3), 9-Hexadecenoic acid (4) and Pentadecanoic acid (5). Other compounds were 10-Octadecenoic acid, methyl ester (6), Hexadecanoic acid, 2-hydroxy-1-(hydroxym) (7) and 11, 14-Eicosadienoic acid, methyl ester (8). These compounds have been recognised to possess ABSTRACT Background: Plant based products are recognised as sources of drugs for treatment of diseases. Objective: The study aimed at predicting the physicochemical, pharmacokinetics, drug-likeness and toxicity of the compounds identified from the methanolic Encephalartos ferox fruit extract. Methods: The physicochemical, pharmacokinetics properties and bioactive scores of the compounds were predicted using SwissADME and Molinspiration computational tools. Drug-likeness of the compounds was evaluated based on the Lipinski rule of five (Ro5). In silico mutagenicity, carcinogenicity and inhibition of human ether-ago go related (hERG) gene were also investigated using PreADMET web tool. Results: The physicochemical properties showed the compounds, except 9-Octadecenoic acid, 1, 2, 3-propanetriyl ester to adhere to Ro5. The evaluation of their inhibitory effects profile in several cytochrome P450 isoforms indicate that all the compounds are not the inhibitors of CYP2C19 and CYP3A4 whereas some inhibited CYP1A2, CYP2C9 and CYP2D6. The drug-likeness evaluation employed Ro5 as a filter and all compounds complied with it except for 9-Octadecenoic acid, 1, 2, 3-propanetriyl ester. About 50% of the tested compound were found to be safe as they did not exhibit antimutagenic and carcinogenic effects. Moreover, the risk of inhibition of hERG gene revealed to be low to medium risk depending on the compound. Conclusion: The calculated physicochemical and pharmacokinetic properties suggest that most of the compounds are safe and have promising oral bioavailability.

Background: Although literature reports the therapeutic properties of Encephalartos ferox, there are limited pharmacological studies of its fruit. Objective: This study sought to evaluate the antibacterial, antioxidant, anti-quorum sensing, and in vitro cytotoxic activities of the methanolic E. ferox fruit extract. Methods: The chemical constituent of the methanolic fruit extract was analysed using gas chromatography-mass spectrometry. Antibacterial activity of the extract was investigated against Staphylococcus aureus (ATCC 25923), Bacillus cereus (ATCC 10102), Escherichia coli (ATCC 25922) and Pseudomonas aeruginosa (ATCC 27853) using the broth dilution method. The standard 2.2-diphenyl-1-picrylhydrazyl (DPPH) and 2.2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) methods were used to evaluate the scavenging activities of the extract. Anti-quorum sensing activity was assessed against biosensor strain-Chromobacterium violaceum (ATCC 12472). Cytotoxicity in HepG2 cells was investigated using the tetrazolium-based colorimetric (MTT) assay. Results: The extract revealed eight volatile compounds with cis-Vaccenic acid (87.06%) and 9-Octadecenoic acid, 1,2,3-propanetriyl ester (5.21%) as the major components. Antibacterial activity against all tested strains with minimum inhibitory concentration range of 1.56 -12.5 mg/mL was observed. The DPPH and ABTS assays demonstrated scavenging activities with the median inhibitory concentration (IC 50 ) values of 0.09 mg/mL and 0.003 mg/mL, respectively. The extract also displayed strong anti-quorum sensing activity with 93% inhibition of violacein production at 25 mg/mL. A half maximum inhibitory concentration (IC 50 ) of 5370 µg/mL was computed in HepG2 cells. Conclusion:The extract has potential to be used as a source of therapeutic compounds in pharmaceutical applications.