Investigation into the Synthesis and Antibacterial Activity of Curcumin Analogues against Gram-positive and Gram-negative Bacteria

Bacteria cause important infectious diseases, and the rapid development of resistance is a serious concern. Therefore, investigating novel drugs from natural or synthetic sources with potent antibacterial activity against resistant strains is highly desirable. Curcumin is a natural phenolic compound isolated from turmeric; it possesses a wide range of pharmacological activities including antimicrobial effects. One challenge with curcumin is poor solubility/bioavailability; therefore it is of interest to investigate curcumin analogues (CAs) with potentially enhanced antibacterial activity and bioavailability. The aims were to synthesise CAs, establish their antibacterial activity, improve the solubility and assess their cytotoxicity. A total of 22 CAs were synthesised via a Claisen-Schmidt condensation reaction and characterised prior to determining antibacterial activity against Staphylococcus aureus , Staphylococcus epidermidis , MRSA, MSSA, Escherichia coli and Pseudomonas aeruginosa . Initial activity was demonstrated by 15 CAs, with 7 active against all isolates. The cytotoxicity assessment against HeLa and HaCaT cells using a PrestoBlue assay showed no toxicity towards either cell line. However, to improve solubility, the CAs were combined with albumin using a solid dispersion technique which, although resulting in significantly enhanced solubility, did not improve nor reduce antibacterial activity when re-tested using the same bacteria and assays as previously mentioned. In conclusion, the potential antibacterial action, improved solubility and lack of cytotoxicity shows that these CAs have the capacity to become new drugs with the aim to slow the emergence of resistance, but further testing is required to show their full potential. Publication History Article published online: 16 November 2023 © 2023. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany