In recent years, fungal infections have emerged as a significant health concern across veterinary species, especially in livestock such as cattle, where fungal diseases can result in considerable economic losses, as well as in humans. In particular, Aspergillus species, notably Aspergillus flavus and Aspergillus versicolor, are opportunistic pathogens that pose a threat to both animals and humans. This study focuses on the synthesis and antifungal evaluation of novel 9-fluorenylmethoxycarbonyl (Fmoc)-protected 1,2,4-triazolyl-α-amino acids and their dipeptides, designed to combat fungal pathogens. More in detail, we evaluated their antifungal activity against various species, including Aspergillus versicolor (ATCC 12134) and Aspergillus flavus (ATCC 10567). The results indicated that dipeptide 7a exhibited promising antifungal activity against Aspergillus versicolor with an IC50 value of 169.94 µM, demonstrating greater potency than fluconazole, a standard treatment for fungal infections, which showed an IC50 of 254.01 µM. Notably, dipeptide 7a showed slightly enhanced antifungal efficacy compared to fluconazole also in Aspergillus flavus (IC50 176.69 µM vs. 184.64 µM), suggesting that this dipeptide might be more potent even against this strain. Remarkably, 3a and 7a are also more potent than fluconazole against A. candidus 10711. On the other hand, the protected amino acid 3a demonstrated consistent inhibition across all tested Aspergillus strains, but with an IC50 value of 267.86 µM for Aspergillus flavus, it was less potent than fluconazole (IC50 184.64 µM), still showing some potential as a good antifungal molecule. Overall, our findings indicate that the synthesized 1,2,4-triazolyl derivatives 3a and 7a hold significant promise as potential antifungal agents in treating Aspergillus-induced diseases in cattle, as well as for broader applications in human health. Our mechanistic studies based on molecular docking revealed that compounds 3a and 7a bind to the same region of the sterol 14-α demethylase as fluconazole. Given the rising concerns about antifungal resistance, these amino acid derivatives, with their unique bioactive structures, could serve as a novel class of therapeutic agents. Further research into their in vivo efficacy and safety profiles is warranted to fully realize their potential as antifungal drugs in clinical and agricultural settings.

In recent years, fungal infections have emerged as a significant health concern across veterinary species, especially in livestock such as cattle, where fungal diseases can result in considerable economic losses. Aspergillus species, notably Aspergillus flavus and Aspergillus versicolor, are opportunistic pathogens that pose a threat to both animals and humans. In cattle, Aspergillus infections can lead to mycotic abortion, primarily in late pregnancy, and cause respiratory and gastrointestinal issues. As the incidence of such infections rises, effective antifungal therapies are needed, particularly in the face of increasing antifungal resistance. This study focuses on the synthesis and antifungal evaluation of novel Fmoc-protected 1,2,4-triazolyl-α-amino acids (5 and 6) and their dipeptides (8 and 9), designed to combat fungal pathogens with a targeted and po-tentially safer profile compared to traditional antifungal agents like fluconazole. Through opti-mized precipitation techniques and the activated ester method, we synthesized the compounds and evaluated their antifungal activity against Aspergillus versicolor (ATCC 12134) and Aspergillus flavus (ATCC 10567). The results showed that dipeptide (8) demonstrated promising antifungal activity at 0.16 mL, comparable to fluconazole, a standard treatment for fungal infections. Notably, increasing the concentration of fluconazole to 0.33 mL did not improve its antifungal efficacy, while the dipeptide's effect was enhanced with increased dosage, suggesting the potential of these dipeptides as more potent or selective antifungal agents. In contrast, the protected amino acid (5) exhibited consistent inhibition across all tested concentrations, aligning with the effects observed for fluconazole at higher concentrations. The increasing prevalence of fungal infections in im-munocompromised animals, coupled with the limited number of effective antifungal drugs, underscores the need for innovative therapeutic approaches. In cattle, Aspergillus infections can have devastating consequences for both animal health and agricultural productivity, with affected herds experiencing reduced milk production, poor fertility, and in severe cases, abortion. As conventional antifungal treatments may pose risks of resistance development or adverse side effects, novel antifungal peptides, such as the synthesized dipeptides in this study, present a promising alternative. These compounds offer the dual benefits of high bioactivity against pathogens like Aspergillus species and the potential for reduced resistance due to their distinct mechanisms of action. Our findings indicate that the synthesized 1,2,4-triazolyl dipeptides (8 and 9) hold significant promise as potential antifungal agents, not only for veterinary use in treating Aspergillus-induced diseases in cattle but also for broader applications in human and animal health. Given the rising concerns of antifungal resistance, these peptides, with their unique bio-active structures, could serve as a novel class of therapeutic agents with enhanced specificity and fewer side effects. Further research into their mechanism of action, in vivo efficacy, and safety profiles is warranted to fully realize their potential as antifungal drugs in clinical and agricultural settings.

5-Substituted 2,4-dimethyl-1,6-dihydropyrimidin-6-ones reacted with aromatic aldehydes to give 5-substituted 2-[(E)-2-arylethenyl]pyrimidin-6-ones, and the reaction of 5-(4-fluorobenzyl)-2,6-dimethylpyrimi­din-4(3H)-one with 4-fluorobenzaldehyde produced 5-(4-fluorobenzyl)-2,6-bis[(E)-2-(4-fluorophenyl)ethenyl]­pyrimidin-4(3H)-one. Uracil and 5-fluorouracil were alkylated with 2-(chloromethyl)-4-methoxybenzaldehyde, and the resulting 3-[2,4-dioxo- and 5-fluoro-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)methyl]-4-methoxy­benz­aldehydes were condensed with 5-substituted 2,4-dimethyl-1,6-dihydropyrimidin-6-ones to obtain 1-(5-{(E)-2-[5-(butyl, arylmethyl)-4-methyl-6-oxo-1,6-dihydropyrimidin-2-yl]ethenyl}-2-methoxybenzyl)­uracil, -5-fluorouracil, and -5-bromouracil. The synthesized compounds were evaluated for their antibacterial, antitumor, and anti-monoaminoxidase activities, and their molecular docking to some biological targets was performed.

Bis-1,3,4-oxadiazoles and bis-1,3,4-thiadiazoles with aryl and alkyl linkers have been synthesized. The pharmacophore electron-deficient groups (carboxylic, nitrile) have been introduced into the molecule to increase their hydrophilicity and potential biological activity. Functionalized compounds have demonstrated a new type of biological activity, i.e., inhibition of lipid oxidation revealed as a decrease in the amount of MDA.

Methods have been developed for the synthesis of novel fused pyrano[4,3-b]pyridine derivatives from ethyl 3-amino-4-(furan-2-yl)-7,7-dimethyl-7,8-dihydro-5H-pyrano[4,3-b]thieno[3,2-e]pyridine-2-carbox­ylate. Reactions of its 3-(phenoxycarbonyl)amino derivative with primary and secondary amines have been studied. The reactions with primary amine were accompanied by cyclization with the formation of fused pyrimidines. In the reactions with secondary amines, the product structure depended on the conditions. The synthesized compounds showed a weak antibacterial activity.