Abstract
Antimicrobial resistance (AMR) is a threat to the prevention and treatment of the increasing range of infectious diseases. There is therefore the need for renewed efforts into antimicrobial discovery and development to combat the menace. The antimicrobial activity of plumbagin isolated from roots of Plumbago zeylanica against selected organisms was evaluated for resistance modulation antimicrobial assay, time-kill kinetics assay, and inhibition of biofilm formation. The minimum inhibitory concentrations (MICs) of plumbagin and standard drugs were determined via the broth microdilution method to be 0.5 to 8 μg/mL and 0.25–128 μg/mL, respectively. In the resistance modulation study, MICs of the standard drugs were redetermined in the presence of subinhibitory concentration of plumbagin (4 μg/mL), and plumbagin was found to either potentiate or reduce the activities of these standard drugs with the highest potentiation recorded up to 12-folds for ketoconazole against Candida albicans. Plumbagin was found to be bacteriostatic and fungistatic from the time-kill kinetics study. Plumbagin demonstrated strong inhibition of biofilm formation activity at concentrations of 128, 64, and 32 μg/mL against the test microorganisms compared with ciprofloxacin. Plumbagin has been proved through this study to be a suitable lead compound in antimicrobial resistance drug development.
Highlights
Occurrence of infectious diseases in recent times is attributed mostly to bacteria; a result of prominent resistance strains of organisms to available antibiotics. ese strains include drug-resistant Shigella, multidrug-resistant tuberculosis (MDR-TB), multidrug-resistant Escherichia coli and Neisseria gonorrheae, methicillin-resistant Staphylococcus aureus, and extensively resistant Gram-negative organisms like Pseudomonas aeruginosa and Acinetobacter baumannii [1]
Plumbagin (1.5 g) was obtained as yellowish needle-like crystals with a melting point of 78–80°C. e retardation factor (Rf ) was obtained on a silica gel coated TLC plate developed with mobile phase of petroleum ether-ethyl acetate (70% : 30%) as 0.82
Chemical shifts and peak multiplicities obtained for the compound in the proton NMR analysis in deuterated chloroform (Table 1) bear similarities to the reported values in the literature [13]. e chemical shift integrals revealed a total of 8 protons which is in agreement with the molecular formulae of C11H8O3. e carbon-13 analysis of the compound in deuterated chloroform showed 11 carbons consistent with the molecular formula of plumbagin (Figure 1)
Summary
Occurrence of infectious diseases in recent times is attributed mostly to bacteria; a result of prominent resistance strains of organisms to available antibiotics. ese strains include drug-resistant Shigella, multidrug-resistant tuberculosis (MDR-TB), multidrug-resistant Escherichia coli and Neisseria gonorrheae, methicillin-resistant Staphylococcus aureus, and extensively resistant Gram-negative organisms like Pseudomonas aeruginosa and Acinetobacter baumannii [1]. Occurrence of infectious diseases in recent times is attributed mostly to bacteria; a result of prominent resistance strains of organisms to available antibiotics. Antimicrobial resistance stems from multifactorial causes which include irrational drug use, failure to complete prescribed dosage, prolonged drug use, and therapy duration [2, 3]. Other consequences of AMR include passage of antibiotic resistant diseases to others and increase in economic burden on families, societies, and healthcare systems [4]. Modulation of the activities of commercial antimicrobials by phytochemicals may reverse the mechanism of resistance developed by the organisms [5]. Synergism of conventional antibiotics is being researched into in recent times to establish possible candidates for the discovery and Journal of Tropical Medicine development of new drugs to tackle the menace of antimicrobial resistance [6]
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