Antibacterial activities of thirteen naturally occuring compounds from two Kenyan medicinal plants: Zanthoxylum paracanthum (Mildbr). Kokwaro (Rutaceae) and Dracaena usambarensis Engl. (Asparagaceae) against MDR phenotypes

Abstract

• Root extract of Zanthoxylum paracanthum with good antibacterial activities. • Efflux pump inhibitor improved antimicrobial activities of Z. paracanthum extract. • All compounds exhibited activities on at least 2/13 bacteria tested. • Nitrogen-containing compounds showed the best activities against bacteria tested. • The phenolic amide, 1 was bactericidal against the standard and MDR isolates. The antibacterial potency of thirteen compounds reported from two distinct genera, Zanthoxylum (Rutaceae) and Dracaena (Asparagaceae) against a panel of sensitive and multi-drug resistant Gram-positive and Gram-negative bacteria is described. The minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) determinations on the tested bacteria were established using modified rapid iodonitrotetrazolium chloride (INT) colorimetric assay. The root extract (50% MeOH/CH 2 Cl 2 ) of Zanthoxylum paracanthum was also combined with an efflux pump inhibitor, phenylalanine arginine β-naphthylamide (PAβN) (at 30 μg/mL), to evaluate the role of efflux pumps in the susceptibility of bacteria. Structure-Activity-Relationship (SAR) of related congeners is also described. The results of the MICs ranged from 4 (against Staphylococcus aureus ) to 16 μg/mL (towards Escherichia coli, Enterobacter aerogenes, Klebsiella pneumoniae, Providencia stuartii, Pseudomonas aeruginosa ) for Z. paracanthum extract and from 16 (against S. aureus MRSA3) to 1024 μg/mL (towards S. aureus ATCC25923 and MRSA3) for the compounds. Addition of phenylalanine arginine β-naphthylamide (PAβN) in the root extract of Z. paracanthum significantly increased the antibacterial potency of the extract against the tested bacteria, with the highest MICs values being observed at 1 μg/mL (against S. aureus and E. coli strains). The root extract of Z. paracanthum and most of the compounds exhibited an MIC/MBC ≤ 4 except for compound 1 , indicating their bactericidal status. Overall, this study provides baseline information on the antibacterial profiles of the studied samples against both Gram-positive and Gram-negative pathogenic bacteria. Structure modification of the moderately active compounds originating from Z. paracanthum and Dracaena usambarensis should be attempted in future studies towards the improvement of their antibacterial potencies.