A hybrid of six (6) 4-hydroxyindole azo compounds was synthesised by the diazotization and coupling strategy via electrophilic aromatic substitution reaction. Characterisation by Infrared and UV-Vis spectroscopic studies was carried out and the antimicrobial activity and structure-activity relationship were explored. Amongst the compounds, 4d was the most active against Pseudomonas aeruginosa than the other organisms from the high-throughput spot culture growth inhibition (HTSPOTi) antimicrobial assay. According to the resistant modulation study, the compounds did not show significant activity against the panel of pathogens used. Furthermore, compounds 4a and 4f inhibited biofilm formation in Pseudomonas aeruginosa and Staphylococcus aureus at 70% (31.25 µg/mL) and 57% (125 (µg/mL) respectively. Additionally, 4c and 4e have biofilm inhibition potential against Pseudomonas aeruginosa and Staphylococcus aureus which are implicated in antimicrobial resistance. Hence, the compounds are promising leads with potential to be developed into new antibacterial agents to combat the menace of antimicrobial resistance.
The bulbs of Allium species are a known source of antibacterial phytochemicals. Anti-infective, efflux pump and biofilm inhibitory activities of bulb extracts of selected Ghanaian shallots Allium cepa var aggregatum were evaluated using the HT-SPOTi assay and other whole-cell phenotypic screening techniques to determine their possible mechanisms of action. Ethanol and aqueous extracts of white A. cepa inhibited the growth of Mycobacterium smegmatis mc2 155 and Escherichia coli, respectively. The majority of the Allium extracts significantly (p < 0.05) exhibited efflux pump inhibitory activity against all the acid-fast, Gram-positive and Gram-negative strains used. Hexane and chloroform extract of the pink A. cepa and the aqueous extract of the white A. cepa significantly inhibited M. smegmatis biofilm formation. For Pseudomonas aeruginosa, the inhibition was observed at 250 µg/mL for the aqueous extract (~77.34%) and 125 µg/mL for the hexane extract (~76.51%). The results suggest that Ghanaian shallots could potentially be useful when further developed to tackle antimicrobial resistance, particularly in tuberculosis (TB).
Biofilms, are vastly structured surface-associated communities of microorganisms, enclosed within a self-produced extracellular matrix. Microorganisms, especially bacteria are able to form complex structures known as biofilms. The presence of biofilms especially in health care settings increases resistance to antimicrobial agents which poses a major health problem. This is because biofilm-associated persistent infections are difficult to treat due to the presence of multidrug-resistant microorganisms. This chapter will give an idea about documented agents including isolated compounds, crude extracts, decoctions, fractions, etc. obtained from natural sources such as plants, bacteria, fungi, sponge and algae with antibiofilm activities. Furthermore, we have done phylogenetic analysis to identify plant families most prolific in producing plant species and compounds with good antibiofilm properties so as to aid in prioritizing plant species to investigate in future studies. The data in this chapter will help serve as valuable information and guidance for future antimicrobial development.
Introduction: Antimicrobial resistance has increasingly been a global health concern over the past decades and that has necessitated the quest to increase the pool of antibiotics.
Methods: Five (5) azo compounds were synthesised by diazotization and coupling procedures with yields of 60 – 92%. They were characterized by melting point determination, Ultra-Violet Visible, and Infra-red spectroscopy. High-throughput spot culture growth inhibition (HT-SPOTi) antimicrobial assay was used to evaluate the compounds. Computational studies was also employed to predict some pharmacokinetic properties of the azo compounds
Results: From the in silico studies, none of the compounds violated Lipinski’s rule and therefore, have the potential to be developed into an oral drug. They also showed Total Polar Surface Area (TPSA) values < 140 A2 (74.91 – 100.98 A2) and percentage absorption of 74 – 83 %. They were placed in category III of acute oral drugs. From the high-throughput spot culture growth inhibition antimicrobial assay, all the compounds possessed inhibitory activity against the ESKAPE human pathogens and Mycobacterium smegmatis, with MICs range of 3.9 \(\geq\) 500 \(\mu g/mL\). Except for 4e which showed liver toxicity, all the compounds demonstrated mutagenic and hepatotoxic tendencies. The modulatory assay of the azo compounds revealed that 4c and 4e modulated the antimicrobial activity of ciprofloxacin against Pseudomonas aeruginosa and Staphylococcus aureus. 4c and 4e also modulated the antimicrobial activity of rifampicin against Mycobacterium smegmatis. Exploiting the ability of 4c and 4e to act by a mode of action revealed that they have biofilm formation inhibitory potential.
Conclusion: Compounds 4c and 4e exhibited the best antimicrobial activity in terms of resistant modulation and biofilm inhibition against Pseudomonas aeruginosa, Staphylococcus aureus and Mycobacterium smegmatis.
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