Examination of the antibacterial activities of some semi-synthetic chalcone-derivatives alone and in combination with polymyxin B.

Medu, Erere Ohwofasa

Abstract

Bacterial resistance is an increasing challenge across the world, which means that there is an urgent need for the rational development of antibacterial compounds that have either novel or multiple mechanisms of action. This study demonstrated that two chalcone derivatives - F1 and F23 - had MICs from 16 mg/ml to over 512 mg/ml, when used against two plant pathogens (P. caratovoram and C. michiganensis, subsp. michiganensis) and other important clinical bateria. Both compounds also demonstrated an MIC of 32 mg/ml when used against the quinolone-resistant S. aureus. Though individually weak in terms of their activity, each semi-synthetic agent also displayed notable synergistic action when used in conjunction with polymyxin B against S. aureus, C. violaceum, E. coli and PS. aeruginosa. In these cases, they demonstrated FICs from less than 0.093 to 2. The compounds also demonstrated a FIC index of less than 0.093 when applied with polymyxin B against Neisseriaceae C. violaceum, and were found to have the capacity to extend the spectrum of activity of polymyxin B to include Gram-positive S. aureus species. F1 was found to inhibit the replication of staphylococcal in broth. Combining either F1 or F23 with polymyxin B was found to institute a metabolic blockage in S. aureus and other bacterial species, as determined through a modified MTT reduction assay. The combined agents inflicted major disruptions to the S. aureus cytoplasmic membrane bilayer, as evidenced by the release of intracellular potassium and the influx of Sytox Green fluorescent stain. Notable levels of potential dissipation in the cell membrane, leakage of intracellular potassium ions and blockage of reducing enzymes' activities all occurred within the first thirty minutes. This was far sooner than any significant loss in cell viability - usually recorded after four to eight hours - suggesting that these activities were prerequisites to cell death. In erythrocyte lysis assay, the lowest degree of haemolysis was displayed by the synergistic combinations of 128 mg/ml of either F1 or F23 with 128 mg/ml of polymyxin B, followed by that occurring with 32 mg/ml of either compound combined with 256 mg/ml of the polypeptide antibiotic. In conclusion, further modifications aimed at improving the aqueous solubility of these chalcone derivatives - as well as the antibacterial activity recorded for certain combination concentrations of polymyxin B with either of these semi-synthetic agents - may be required before potential external formulations can be considered. Such preparations may include antiseptic creams, lotions, ointments or aerosols that could be applied with nebulizers in targeted delivery for cases such as cystic fibrosis.

Citation

MEDU, E.O. 2013. Examination of the antibacterial activities of some semi-synthetic chalcone-derivatives alone and in combination with polymyxin B. Robert Gordon University, PhD thesis.

• Thesis Type: Thesis
• Deposit Date: Jul 23, 2013
• Publicly Available Date: Jul 23, 2013
• Keywords: Flavonoids; Chalconederivatives; Polymyxin Bcolistin; Chequerboard assay; Time course viability study; Fluorescence microscopy; Intracellular potassium ion; Flame emission spectrophotometry
• Public URL: http://hdl.handle.net/10059/832
• Contract Date: Jul 23, 2013
• Award Date: May 31, 2013