In this review, we present reports on the immunoregulatory properties of isoxazole derivatives classified into several categories, such as immunosuppressive, anti-inflammatory, immunoregulatory, and immunostimulatory compounds. The compounds were tested in various models using resident cells from rodents and humans, cell lines, and experimental animal disease models corresponding to human clinical situations. Beneficial features of the described isoxazole derivatives include low toxicity and good bioactivity at low doses. In a majority of studies, the activities of investigated compounds were comparable or even higher than registered reference drugs. Whenever possible, a plausible mechanism of action of the investigated compounds and their potential therapeutic utility were proposed. Among the described compounds, particular attention was paid to the class of immune stimulators with a potential application in chemotherapy patients.

Heterocyclic moieties, especially five and six-membered rings containing nitrogen, oxygen or sulfur atoms, are broadly distributed in nature. Among them, synthetic and natural alike are pharmacologically active compounds and have always been at the forefront of attention due to their pharmacological properties. Heterocycles can be divided into different groups based on the presence of characteristic structural motifs. The presence of β-amino acid and heterocyclic core in one compound is very interesting; additionally, it very often plays a vital role in their biological activity. Usually, such compounds are not considered to be chemicals containing a β-amino acid motif; however, considering them as this class of compounds may open new routes of their preparation and application as new drug precursors or even drugs. The possibility of their application as nonproteinogenic amino acid residues in peptide or peptide derivatives synthesis to prepare a new class of compounds is also promising. This review highlights the actual state of knowledge about β-amino acid moiety-containing heterocycles presenting antiviral, anti-inflammatory, antibacterial compounds, anaplastic lymphoma kinase (ALK) inhibitors, as well as agonist and antagonists of the receptors.

The microbial, biofilm-based infections of chronic wounds are one of the major challenges of contemporary medicine. The use of topically administered antiseptic agents is essential to treat wound-infecting microorganisms. Due to observed microbial tolerance/resistance against specific clinically-used antiseptics, the search for new, efficient agents is of pivotal meaning. Therefore, in this work, 15 isoxazole derivatives were scrutinized against leading biofilm wound pathogens Staphylococcus aureus and Pseudomonas aeruginosa, and against Candida albicans fungus. For this purpose, the minimal inhibitory concentration, biofilm reduction in microtitrate plates, modified disk diffusion methods and antibiofilm dressing activity measurement methods were applied. Moreover, the cytotoxicity and cytocompatibility of derivatives was tested toward wound bed-forming cells, referred to as fibroblasts, using normative methods. Obtained results revealed that all isoxazole derivatives displayed antimicrobial activity and low cytotoxic effect, but antimicrobial activity of two derivatives, 2-(cyclohexylamino)-1-(5-nitrothiophen-2-yl)-2-oxoethyl 5-amino-3-methyl-1,2-oxazole-4-carboxylate (PUB9) and 2-(benzylamino)-1-(5-nitrothiophen-2-yl)-2-oxoethyl 5-amino-3-methyl-1,2-oxazole-4-carboxylate (PUB10), was noticeably higher compared to the other compounds analyzed, especially PUB9 with regard to Staphylococcus aureus, with a minimal inhibitory concentration more than x1000 lower compared to the remaining derivatives. The PUB9 and PUB10 derivatives were able to reduce more than 90% of biofilm-forming cells, regardless of the species, displaying at the same time none (PUB9) or moderate (PUB10) cytotoxicity against fibroblasts and high (PUB9) or moderate (PUB10) cytocompatibility against these wound cells. Therefore, taking into consideration the clinical demand for new antiseptic agents for non-healing wound treatment, PUB9 seems to be a promising candidate to be further tested in advanced animal models and later, if satisfactory results are obtained, in the clinical setting.

Heterocyclic compounds are a common subject in the field of medicinal chemistry due to their numerous pharmaceutical applications. Among these, nitrogen- and oxygen-containing five-membered heterocyclic rings, namely oxazole and isoxazole, are particularly significant, exhibiting a broad spectrum of biological activities. Molecular hybridization, the process that enables the fusion of bioactive scaffolds, is a powerful strategy for the development of novel compounds characterized by enhanced or multitarget activities. This review focuses on hybrids incorporating linked oxazole and/or isoxazole moieties (i.e., isoxazole–oxazole and isoxazole–isoxazole hybrids), drawing upon peer-reviewed research articles and international patents from 1995 to the end of 2024. The overview systematically presents the diverse biological activities reported for the isoxazole–(iso)oxazole hybrids, including anticancer, antibacterial, antitubercular, anti-inflammatory, and antidepressant effects, alongside their corresponding chemical structures. Our analysis of the literature highlights the structural versatility and therapeutic potential of this important class of heterocyclic hybrids.

Microbiological communities have a significant impact on health and disease. Candida are ubiquitous fungal pathogens that colonize the mucosal surfaces of the genital, urinary, respiratory, and gastrointestinal tracts, as well as the oral cavity. If the immune system is inadequate, then Candida infections may pose a significant threat. Due to the limited number of clinically approved drugs for the treatment of Candida albicans-based infections and the rapid emergence of resistance to the existing antifungals, a novel series of isoxazole-based derivatives was synthesized and evaluated in vitro for their anti-Candida potential. Two compounds, PUB14 and PUB17, displayed selective antifungal activity without negatively affecting beneficial microbiota, such as Lactobacillus sp., at the same time. Moreover, these compounds exhibited significantly lower cytotoxicity in comparison to conventionally applied local antimicrobial (octenidine dihydrochloride), indicating their potential for safe and effective clinical application in conditions such as vulvovaginal candidiasis. The selective antifungal activity of PUB14 and PUB17 against C. albicans, coupled with its absence of antibacterial effects and minimal cytotoxicity towards HeLa cells, suggests a targeted mechanism of action that warrants further investigation. Consideration of the need to search for new antifungal agents and the discovery of an antifungal potential drug that does not inhibit lactobacilli growth could be a potential strategy to prevent and combat vulvovaginal candidiasis. This striking capacity to eradicate biofilm formed by Candida reveals a new approach to eradicating biofilms and sheds light on isoxazole-based derivatives as promising anti-biofilm drugs.

The distinct structure of cationic organic compounds plays a pivotal role in enhancing their water solubility, which in turn influences their bioavailability. A representative of these compounds, which contains a delocalized charge, is 5-amino-2-(5-amino-3-methyl-1,2-oxazol-4-yl)-3-methyl-2,3-dihydro-1,3,4-oxadiazol-2-ylium bromide (ED). The high-water solubility of ED obviates the need for potentially harmful solvents during in vitro testing. The antibacterial and antifungal activities of the ED compound were assessed in vitro using the microtiter plate method and a biocellulose-based biofilm model. Additionally, its cytotoxic effects on wound bed fibroblasts and keratinocytes were examined. The antistaphylococcal activity of ED was also evaluated using an in vivo larvae model of Galleria mellonella. Results indicated that ED was more effective against Gram-positive bacteria than Gram-negative ones, exhibiting bactericidal properties. Furthermore, ED demonstrated greater efficacy against biofilms formed by Gram-positive bacteria. At bactericidal concentrations, ED was non-cytotoxic to fibroblasts and keratinocytes. In in vivo tests, ED was non-toxic to the larvae. When co-injected with a high load of S. aureus, it reduced the average larval mortality by approximately 40%. These findings suggest that ED holds promise for further evaluation as a potential treatment for biofilm-based wound infections, especially those caused by Gram-positive pathogens like S. aureus.