Lala Stepanyan

Background/Objectives: Antimicrobial peptides (AMPs), evolutionarily conserved components of innate immunity characterized by their broad-spectrum efficacy and minimal resistance development, are increasingly recognized as promising therapeutic candidates. This review aims to integrate current knowledge concerning natural and synthetic antimicrobial peptides and their therapeutic effectiveness in addressing gastrointestinal infections. Methods: A literature review was performed, evaluating recent peer-reviewed studies on AMPs. The research concentrated on their molecular mechanisms of action, antimicrobial spectrum, and their interactions with standard antibiotics. More in detail, the peptide classes examined herein included defensins, cathelicidins, histatins, and various natural peptides such as lactoferricin, protamines, RegIII, and hepcidin, along with synthetic analogs like WR12, D-IK8, MSI-78, and IMX942. Results: Natural AMPs demonstrated significant antimicrobial and immunomodulatory effects against Escherichia coli, Klebsiella pneumoniae, Salmonella spp., and Shigella spp. Beyond direct antimicrobial activity, antimicrobial peptides act as integrated anti-infective agents not only by modulating host–microbiota interactions, but also preserving epithelial barrier integrity, and limiting inflammation, thereby offering a multifaceted strategy to control gastrointestinal infections. On the other hand, synthetic peptides showed improved stability, reduced cytotoxicity, and synergistic interactions with antibiotics, which suggests that they could be used either alone or in combination with other treatments. Conclusions: AMPs constitute a promising category endowed with anti-infective activity, especially for therapy of intestinal diseases, which is attributed to their distinctive anti-infective mechanisms, immune-modulating characteristics, and a relatively low propensity for resistance development compared to conventional antibiotics. However, more clinical trials and improvements to their formulation are needed to translate promising in vitro results into reliable patient outcomes.

Background/Objectives: Antimicrobial peptides (AMPs), evolutionarily conserved components of innate immunity characterized by their broad-spectrum efficacy and minimal resistance development, are increasingly recognized as promising therapeutic candidates. This review aims to integrate current knowledge concerning natural and synthetic antimicrobial peptides and their therapeutic effectiveness in addressing gastrointestinal infections. Methods: A literature review was performed, evaluating recent peer-reviewed studies on AMPs. The research concentrated on their molecular mechanisms of action, antimicrobial spectrum, as well as on their interactions with standard antibiotics. More in detail, the peptide classes examined herein included defensins, cathelicidins, histatins, and various natural peptides such as lactoferricin, protamines, RegIII, and hepcidin, along with synthetic analogs like WR12, D-IK8, MSI-78, IMX942. Results: Natural AMPs demonstrated significant antimicrobial and immunomodulatory effects against Escherichia coli, Klebsiella pneumoniae, Salmonella spp., and Shigella spp. Beyond direct antimicrobial activity, intestinal antimicrobial peptides act as integrated anti-infective agents by modulating host–microbiota interactions, preserving epithelial barrier integrity, and limiting inflammation, thereby offering a multifaceted strategy to control gastrointestinal infections. On the other hand, synthetic peptides showed better stability, less toxicity, and synergistic interactions with antibiotics, which suggests that they could be used either alone or in combination with other treatments. Conclusions: AMPs constitute a promising category endowed with anti-infective activity especially for therapy of intestinal diseases, which is attributed to their distinctive anti-infective mechanisms, immune-modulating characteristics, and a relatively low propensity for resistance development compared to conventional antibiotics. However, more clinical trials and improvements to their formulation are needed to translate promising in vitro results into reliable patient outcomes.

Intracellular parasitic infections continue to pose significant public health and veterinary challenges globally, driven by their ability to evade immune responses, persist within host cells, and spread through complex transmission pathways. Caused by a diverse array of protozoan, helminthic, and arthropod-borne parasites, these infections, such as toxoplasmosis, leishmaniasis, and tick-borne diseases, remain prevalent across many regions, often exacerbated by environmental, socio-economic, and ecological factors. This review explores the current knowledge on intracellular parasitic diseases, outlining parasite classification, immune evasion mechanisms, diagnostic difficulties, and control strategies. Special attention is given to recent advancements in vaccine development, with a focus on experimental and licensed vaccines targeting intracellular pathogens. Additionally, the review highlights the importance of a ‘One Health’ approach, integrating human, animal, and environmental health efforts to address the multifaceted nature of parasitic transmission and control. Within this global context, Armenia serves as a case study, offering insight into how local ecological conditions, vector distribution, public health capacity, and social determinants shape the national burden of these infections. Challenges in Armenia, such as limited access to advanced diagnostics, underreporting, and the need for robust surveillance systems, underscore broader regional needs for investment in research, infrastructure, and cross-sectoral collaboration.

We report on the synthesis and characterization of a novel fluorenyl-methoxycarbonyl (Fmoc)-containing thioxo-triazole-bearing dipeptide 5, evaluated for potential therapeutic applications. The compound was tested for its antioxidant and antimicrobial properties, demonstrating significant effects in scavenging reactive oxygen species (ROS) and inhibiting microbial growth, particularly when combined with plant extracts from an endemic Peonia species from the Caucasus. Circular dichroism (CD) binding studies with bovine serum albumin (BSA) and calf thymus DNA revealed important interactions, suggesting the dipeptide’s potential in biomedically relevant conditions that involve DNA modulation. Molecular docking and CD spectra deconvolution provided additional insights into the binding mechanisms and structural characteristics of the formed complexes with the biomolecular targets. The Fmoc group enhances the dipeptide’s lipophilicity, which may facilitate its interaction with cellular membranes, supporting efficient drug delivery. A computational evaluation at the ωB97XD/aug-cc-pVDZ level of theory was carried out, confirming the experimental results and revealing a powerful potential of the peptide as an antioxidant, through FMOs, MEP analysis, and antioxidant mechanism assessments. Together, these findings suggest that this dipeptide could be valuable as an antimicrobial and antioxidant agent, with potential applications in pathologies involving oxidative stress, DNA modulation, and microbial infections.

We report the synthesis and characterization of a novel fluorenyl-methoxycarbonyl (Fmoc)-containing thioxo-triazole-bearing dipeptide Fmoc-(S)-Asp(O-tert-butyl)-(S)-β-(4-phenyl- 3-propyl-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-Ala, evaluated for potential therapeutic ap-plications. The compound was tested for its antioxidant and antimicrobial properties, demon-strating significant effects in scavenging reactive oxygen species (ROS) and inhibiting microbial growth, particularly when combined with plant extracts from an endemic Peonia species from the Caucasus. Circular Dichroism (CD) binding studies with bovine serum albumin (BSA) and calf thymus DNA revealed important interactions, suggesting the dipeptide’s potential in biomedical-ly-relevant conditions that involve DNA modulation. Molecular docking and CD spectra decon-volution provided additional insights into its binding mechanisms and structural characteristics of the formed complexes with the biomolecular targets. The Fmoc group enhances the dipeptide’s lipophilicity, which may facilitate its interaction with cellular membranes, supporting efficient drug delivery. A computational evaluation at B97XD/aug-cc-pVDZ level of theory was carried out, confirming the experimental results and revealing a powerful potential of the peptide as an-tioxidant, throughout FMOs, MEP analysis and antioxidant mechanism assessments. Together, these findings suggest that this dipeptide could be valuable as an antimicrobial and antioxidant agent, with potential applications in pathologies involving oxidative stress, DNA modulation, and microbial infections.

This study explores the neuropharmacological potential of various molecular and amino acid components derived from Syzygium aromaticum (clove), an aromatic spice with a long history of culinary and medicinal use. Key bioactive compounds such as eugenol, α-humulene, β-caryophyllene, gallic acid, quercetin, and luteolin demonstrate antioxidant, anti-inflammatory, and neuroprotective properties by scavenging free radicals, modulating calcium channels, and reducing neuroinflammation and oxidative stress. Moreover, gallic acid and asiatic acid may exhibit protective effects, including neuronal apoptosis inhibition, while other useful properties of clove phytocompounds include NF-κB pathway inhibition, membrane stabilization, and suppression of pro-inflammatory pathways, possibly in neurons or other relevant cell types, further contributing to neuroprotection and cognitive enhancement. Amino acid analysis revealed essential and non-essential amino acids such as aspartic acid, serine, glutamic acid, glycine, histidine, and arginine in various clove parts (buds, fruits, branches, and leaves). These amino acids play crucial roles in neurotransmitter synthesis, immune modulation, antioxidant defense, and metabolic regulation. Collectively, these bioactive molecules and amino acids contribute to clove’s antioxidant, anti-inflammatory, neurotrophic, and neurotransmitter-modulating effects, highlighting its potential as a preventive and therapeutic candidate for neurodegenerative disorders. While preliminary preclinical studies support these neuroprotective properties, further research, including clinical trials, is needed to validate the efficacy and safety of clove-based interventions in neuroprotection.

This study explores the neuropharmacological potential of various molecular and amino acid components derived from Syzygium aromaticum (clove), an aromatic spice with a long history of culinary and medicinal use. Key bioactive compounds such as eugenol, α -humulene, β -caryophyllene, gallic acid, quercetin, and luteolin demonstrate antioxidant, anti-inflammatory, and neuroprotective properties by scavenging free radicals, modulating calcium channels, and reducing neuroinflammation and oxidative stress. Moreover, gallic acid and asiatic acid exhibit protective effects, including apoptosis inhibition, while other useful properties of clove phytocompounds include NF-κB pathway inhibition, membrane stabilization, and suppression of pro-inflammatory pathways, further contributing to neuroprotection and cognitive enhancement. Amino acid analysis revealed essential and non-essential amino acids such as aspartic acid, serine, glutamic acid, glycine, histidine, and arginine in various clove parts (buds, fruits, branches, and leaves). These amino acids play crucial roles in neurotransmitter synthesis, immune modulation, antioxidant defense, and metabolic regulation. Collectively, these bioactive molecules and amino acids contribute to clove’s antioxidant, anti-inflammatory, neurotrophic, and neurotransmitter-modulating effects, highlighting its potential as a preventive and therapeutic candidate for neurodegenerative disorders. While preliminary preclinical studies support these neuroprotective properties, further research, including clinical trials, is needed to validate the efficacy and safety of clove-based interventions in neuroprotection.

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.

New dipeptides containing derivatives of phenylalanine, N-tert-butoxycarbonyl-(S)-alanyl-(S)-α-methylphenylalanine and N-tert-butoxycarbonyl-(S)-alanyl-(S)-α-methyl-4-fluorophenylalanine, were synthesized. The antifungal activity of initial non-protein amino acids, derivatives of phenylalanine, and synthesized dipeptides was studied by selecting widely spread pathogenic and conditionally pathogenic fungal strains as test fungi: Aspergillus versicolor 12134, A. flavus 10567, A. candidus 10711, Penicillium chrysogenum 8190, P. aurantiogriseum 12053, P. funiculosum 8258, Alternaria alternata 8126, Ulocladium botrytis 12027, and Aureobasidium pullulans 8269. The studies showed that the antifungal activity of (S)-α-methyl-phenylalanine amino acid was pronounced against P. aurantiogriseum 12053 and Ulocladium botrytis 12027 fungal strains when applied at a concentration of 0.177 mg/ml; the dipeptide containing the mentioned amino acid showed a high inhibitory effect on the P. aurantiogriseum 12053 strain, exhibiting the same degree of inhibition at concentrations of 0.232 mg/ml and higher. (S)-α-methyl-4-fluorophenylalanine amino acid most significantly suppressed the growth of P. aurantiogriseum 12053, P. funiculosum 8258, Ulocladium botrytis 12027, and Aureobasidium pullulans 8269 fungal strains when a 0.195 mg/ml solution was used. The growth of the P. aurantiogriseum 12053 strain was inhibited even at a lower concentration of 0.13 mg/ml; the dipeptide containing the amino acid significantly inhibited the growth of the P. aurantiogriseum 12053 strain when applied at a concentration of 0.369 mg/ml.