Exploring the Potential of Anacardic Acid, its Natural and Synthetic Analogues, and Nanoformulations as a Potential Antibacterial Agent, including Multidrug-resistant Bacteria: A Comprehensive Review.

The increasing rise of multidrug-resistant bacteria necessitates an urgent need for the discovery of novel antibacterial agents. Natural products have long been a source for identifying and isolating novel antibacterial agents. Anacardic acids (AAs), a phenolic lipid isolated from solventextracted cashew nutshell liquid (CNSL) of Anacardium occidentale (Family Anacardiaceae), have garnered potential attention for their potent antibacterial properties. Besides Anacardium occidentale, different analogues of AAs have also been isolated from various natural sources. These natural and structurally optimized derivatives exhibited potential antibacterial properties against other bacterial strains. Although AAs are associated with a high level of antimicrobial activity against P. acnes, S. mutans, S. pyogenes, H. pylori, and methicillin-resistant S. aureus, their poor physicochemical properties are a major concern for their clinical translation. Encapsulating AAs in nanoformulations could be beneficial, as it can improve their poor pharmacokinetic properties, prevent enzymatic degradation during transport in the body, and facilitate site-specific release, thereby enhancing their therapeutic potential. Among the different nanocarriers studied, zein nanoparticles loaded with anacardic acid showed strong antibiofilm activity against E. faecalis, S. aureus, and P. aeruginosa. In contrast, the DNase-chitosan-coated solid lipid nanoparticles (Ana-SLNs-CH-DNase) demonstrated superior activity in disrupting mature S. aureus biofilms. Additionally, we have discussed the structure-activity relationship and mechanism of action of AAs, where it was found that AAs disrupt cell membrane functioning, inhibit bacterial respiration, quorum sensing, and cellular respiration, among other effects. These findings suggest that AAs and their analogues exhibit promising antibacterial activity, while nanoformulations offer a promising strategy to optimize their therapeutic potential.