This narrative review paper provides an up-to-date overview of the potential of novel synthetic and semisynthetic compounds as antibacterials that target virulence traits in resistant strains. The review focused on research conducted in the last five years and investigated a range of compounds including azoles, indoles, thiophenes, glycopeptides, pleuromutilin derivatives, lactone derivatives, and chalcones. The emergence and spread of antibiotic-resistant bacterial strains is a growing public health concern, and new approaches are urgently needed to combat this threat. One promising approach is to target virulence factors, which are essential for bacterial survival and pathogenesis, but not for bacterial growth. By targeting virulence factors, it may be possible to reduce the severity of bacterial infections without promoting the development of resistance. We discuss the mechanisms of action of the various compounds investigated and their potential as antibacterials. The review highlights the potential of targeting virulence factors as a promising strategy to combat antibiotic resistance and suggests that further research is needed to identify new compounds and optimize their efficacy. The findings of this review suggest that novel synthetic and semisynthetic compounds that target virulence factors have great potential as antibacterials in the fight against antibiotic resistance.

Hesperetin is the aglycone of citrus flavonoid hesperidin. Due to the limited information regarding hesperetin antimicrobial potential and emerging need for novel antimicrobials, we have studied its antimicrobial activity (microdilution assay), antibiofilm activity with different assays in two models (mono- and polymicrobial biofilm), and toxicity (MTT and brine shrimp lethality assays). Hesperetin inhibited growth of all Candida isolates (minimal inhibitory concentration, MIC, 0.165 mg/mL), while it’s inhibitory potential towards Staphylococcus aureus was lower (MIC 4 mg/mL). Hesperetin (0.165 mg/mL) reduced ability of Candida to form biofilms and moderately reduced exopolysaccharide levels in biofilm matrix. Effect on the eradication of 24 h old C. albicans biofilms was promising at 1.320 mg/mL. Inhibition of staphylococcal biofilm formation required higher concentrations of hesperetin ( 1 mg/mL). Hesperetin is efficient in combating growth and biofilm formation of Candida species. However, its antibacterial application should be further examined due to the cytotoxic effects provoked in the antibacterial concentrations.

Paeonia tenuifolia L. (steppe peony) petal extract was proficiently encapsulated into liposomes and biopolymer films in the current work, both times utilizing a single-step procedure. The encapsulation efficiency, size of the particles, and index of polydispersity (PDI), as well as the ζ potential of the obtained liposomes were determined, whereas in the case of films, the test included moisture content and mechanical property assessment. Fourier transform infrared spectroscopy (FT-IR) was used to evaluate the chemical composition and existence of numerous interactions in the systems. All the obtained encapsulates were subjected to antibacterial, antifungal and antibiofilm activity testing of the pathogens associated with human skin. The results indicated that the liposomes prepared using Phospholipon had the highest encapsulation efficiency (72.04%), making them the most favorable ones in the release study as well. The biological assays also revealed that Phospholipon was the most beneficial phospholipid mixture for the preparation of liposomes, whereas the film containing these liposomes did not have the ability to inhibit pathogen growth, making the double encapsulation of P. tenuifolia L. petal extract needless. These findings may be a first step toward the potential use of steppe peony extract-loaded films and liposomes in pharmaceutical and cosmetical industries.

Twelve steroid based hydrazones were in silico evaluated using computer program PASS as antimicrobial agents. The experimental evaluation revealed that all compounds have low to moderate antibacterial activity against all bacteria tested, except for B. cereus with MIC at a range of 0.37–3.00 mg/mL and MBC at 0.75–6.00 mg/mL. The most potent appeared to be compound 11 with MIC/MBC of 0.75/1.5 mg/mL, respectively. The evaluation of antibacterial activity against three resistant strains MRSA, E. coli and P. aeruginosa demonstrated superior activity of compounds against MRSA compared with ampicillin, which did not show bacteriostatic or bactericidal activities. All compounds exhibited good antifungal activity with MIC of 0.37–1.50 mg/mL and MFC of 1.50–3.00 mg/mL, but with different sensitivity against fungi tested. According to docking studies, 14-alpha demethylase inhibition may be responsible for antifungal activity. Two compounds were evaluated for their antibiofilm activity. Finally, drug-likeness and docking prediction were performed.

Wild thyme aerial parts (Serpylli herba) are recognized as a valuable herbal product with antioxidant, anti-inflammatory, and antibacterial effects. Although pharmacopoeial regulations allow its collection exclusively from Thymus serpyllum, substitution with other species is frequent in current practice. This study analyzed the phenolic composition, antioxidant, and enzyme-inhibitory and antimicrobial activity of the hydroethanolic extracts obtained from five Romanian wild thyme species (Thymus alpestris, T. glabrescens, T. panonicus, T. pulcherimus and T. pulegioides). The analysis of individual phenolic constituents was performed through LC-ESI-DAD/MS², while for the in vitro evaluation of antioxidant potential, TEAC, FRAP, DPPH, TBARS and OxHLIA assays were employed. The anti-enzymatic potential was tested in vitro against tyrosinase, α-glucosidase and acetylcholinesterase. High rosmarinic acid contents were quantified in all species (20.06 ± 0.32–80.49 ± 0.001 mg/g dry extract); phenolic acids derivatives (including salvianolic acids) were confirmed as the principal metabolites of T. alpestris and T. glabrescens, while eriodictyol-O-di-hexoside was found exclusively in T. alpestris. All species showed strong antioxidant potential and moderate anti-enzymatic effect against α-glucosidase and acetylcholinesterase, showing no anti-tyrosinase activity. This is the first detailed report on the chemical and biological profile of T. alpestris collected from Romanian spontaneous flora.

Without being aware of their chemical composition, many cultures have used herbaceous peony roots for medicinal purposes. Modern phytopreparations intended for use in human therapy require specific knowledge about the chemistry of peony roots and their biological activities. In this study, ethanol–water extracts were prepared by maceration and microwave- and ultrasound-assisted extractions (MAE and UAE, respectively) in order to obtain bioactive molecules from the roots of Paeonia tenuifolia L., Paeonia peregrina Mill., and Paeonia officinalis L. wild growing in Serbia. Chemical characterization; polyphenol and flavonoid content; antioxidant, multianti-enzymatic, and antibacterial activities of extracts; and in vitro gastrointestinal digestion (GID) of hot water extracts were performed. The strongest anti-cholinesterase activity was observed in PT extracts. The highest anti-ABTS (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) radical potential was observed in PP extracts, whereas against DPPH (2,2-diphenyl-1-picrylhydrazyl radicals), the best results were achieved with PO extracts. Regarding antibacterial activity, extracts were strongly potent against Bacillus cereus. A molecular docking simulation was conducted to gather insights into the binding affinity and interactions of polyphenols and other Paeonia-specific molecules in the active sites of tested enzymes. In vitro GID of Paeonia teas showed a different recovery and behavior of the individual bioactives, with an increased recovery of methyl gallate and digallate and a decreased recovery of paeoniflorin and its derivatives. PT (Gulenovci) and PP (Pirot) extracts obtained by UAE and M were more efficient in the majority of the bioactivity assays. This study represents an initial step toward the possible application of Paeonia root extracts in pharmacy, medicine, and food technologies.