Investigation into the synthesis and antimicrobial activity of curcumin analogues against gram-positive and gram-negative bacteria

Denison, Hannah (2022) Investigation into the synthesis and antimicrobial activity of curcumin analogues against gram-positive and gram-negative bacteria. (PhD thesis), Kingston University, .

Abstract

Bacterial resistance to many current antibiotics continues to spread globally which is a disturbing phenomenon which can lead to serious medical implications. In order to combat this, new compounds from both synthetic and/or natural sources are being investigated. Curcumin is a compound of interest due to its wide range of biological properties but although readily available suffers from a number of disadvantages, particularly solubility, and bioavailability. In this study twenty-four curcumin analogues (CAs) were synthesised using a Claisen-Schmidt condensation reaction prior to characterisation and four were subsequently identified as novel compounds. The antibacterial activity of each was assessed against a panel of relevant Gram-positive and Gram-negative bacteria (Staphylococcus aureus, Staphylococcus epidermidis, methicillin-resistant Staphylococcus aureus, methicillin-sensitive Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa) and their cytotoxicity evaluated against both HeLa and HaCaT cells. Enhancements to the CAs’ initial poor solubility were performed using solid dispersion techniques in combination with bovine serum albumin prior to reassessment of the antibacterial activity. The Minimum Inhibitory Concentration (MIC) results showed that seventeen CAs displayed activity against both Gram-positive and Gram-negative strains with the remaining seven showing selective activity towards one strain, all in the MIC range of 5-20 µg/mL. No CAs were found to elicit cytotoxicity towards the cell lines up to 100 µM and although the solubility was significantly enhanced, the level of antibacterial activity remained the same. Lastly, CA nanoparticles were synthesised as a pilot study to investigate their effect on antibacterial activity. The initial work in this study indicates that a number of these CAs have potential as antibacterial agents, however further work including mechanistic studies and a full in vitro nanoparticle study need to be conducted prior to investigating possible applications such as integration into burn/wound dressings.

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