Untargeted Lipidomics Study of Bipolar Disorder Patients in Serbia.

The Lipidomic profiles of serum samples from patients with bipolar disorder (BD) and healthy controls (C) were explored and compared. The sample cohort included 31 BD patients and 31 control individuals. An untargeted lipidomics study applying liquid chromatography (LC) coupled with high-resolution mass spectrometry (HRMS) was conducted to achieve the lipid profiles. Multivariate statistical analyses (principal component analysis and partial least squares discriminant analysis) were performed, and fifty-six differential lipids were confirmed in BD and controls. Our results pointed to alterations in lipid metabolism, including pathways of glycerophospholipids, sphingolipids, glycerolipids, and sterol lipids, in BD patient sera. This study emphasized the role of lipid pathways in BD, and comprehensive research using the LC-HRMS platform is necessary for future application in the diagnosis and improvement of BD treatments.

GC-FID-MS Based Metabolomics to Access Plum Brandy Quality.

Plum brandy (Slivovitz (en); Sljivovica(sr)) is an alcoholic beverage that is increasingly consumed all over the world. Its quality assessment has become of great importance. In our study, the main volatiles and aroma compounds of 108 non-aged plum brandies originating from three plum cultivars, and fermented using different conditions, were investigated. The chemical profiles obtained after two-step GC-FID-MS analysis were subjected to multivariate data analysis to reveal the peculiarity in different cultivars and fermentation process. Correlation of plum brandy chemical composition with its sensory characteristics obtained by expert commission was also performed. The utilization of PCA and OPLS-DA multivariate analysis methods on GC-FID-MS, enabled discrimination of brandy samples based on differences in plum varieties, pH of plum mash, and addition of selected yeast or enzymes during fermentation. The correlation of brandy GC-FID-MS profiles with their sensory properties was achieved by OPLS multivariate analysis. Proposed workflow confirmed the potential of GC-FID-MS in combination with multivariate data analysis that can be applied to assess the plum brandy quality.

Bat guano-dwelling microbes and antimicrobial properties of the pygidial gland secretion of a troglophilic ground beetle against them.

Bat guano is an important source of microbial diversity in caves and can be a source of potential pathogens. Laemostenus (Pristonychus) punctatus is a guanophilic ground beetle species, which pygidial gland secretion exhibits action against pathogenic and other microbes. The distribution and diversity of microbes in bat guano from a karstic cave were determined in this study. Additionally, antimicrobial activity of the pygidial gland secretion of L. (P.) punctatus against guano-dwelling microbes was tested; minimal inhibitory concentration (MIC) and chemical composition of the secretion were analyzed. In total, 63 different bacterial species and 16 fungal morphotypes were isolated from guano samples by the cultivation method and confirmed using and phenotypic characterization and molecular identification. There was a difference in the composition of certain microorganisms between the sampling points (cave locations) and between the guano layers. The largest number of bacterial isolates belongs to the genera Lysinibacillus and Paenibacillus, while Pseudomonas species were highly abundant at the innermost sampling point. For the guanophilic fungi, the majority are ascomycetes, with Penicillium and Aspergillus as the most dominant genera. Meyerozyma guilliermondii was the only yeast species found in the guano samples. The most sensitive isolates were Enterococcus eurekensis (MIC 0.007 mg/mL) and Escherichia fergusonii (MIC 0.028 mg/mL). The most sensitive fungal isolates were M. guilliermondii, Penicillium expansum, and Trichoderma harzianum (MIC 0.15 mg/mL). This study opens a new possibility for better understanding of ecological relations between microorganisms and troglophilic ground beetles and for detailed investigations of morpho-anatomical aspects of pygidial glands.

Cytotoxic Activity of Riccardin and Perrottetin Derivatives from the Liverwort Lunularia cruciata.

Seven new bisbibenzyls (1-7) were isolated from the methanol extract of the liverwort Lunularia cruciata along with one previously known bibenzyl and five known bisbibenzyls. The structures of compounds 1-7 were elucidated on the basis of the spectroscopic data. These newly isolated bisbibenzyls may be divided into two groups, the acyclic bisbibenzyls, perrottetins (1-3), and the cyclic analogues, riccardins (4-7). Besides standard perrottetin and riccardin structures (1 and 4, respectively), they contain phenanthrene (3 and 5), dihydrophenanthrene (2), and quinone moieties (6 and 7), rarely found in natural products. The new compounds 3 and 5, as well as the known riccardin G, exhibited cytotoxic activity against the A549 lung cancer cell line with IC50 values of 5.0, 5.0, and 2.5 µM, respectively.

Antibacterial and Antibiofilm Activity of Flavonoid and Saponin Derivatives from Atriplex tatarica against Pseudomonas aeruginosa.

A new flavonoid glucoside derivative, patuletin 3 -O-(2- O-feruloyl)-ß-d-glucuronopyranosyl-(1→2)-ß-d-glucopyranoside, named atriplexin IV (1), and three new triterpenoid saponin derivatives, two sulfonylated, ß-d-glucopyranosyl-3 -O-(2- O-sulfo-ß-d-galactopyranosyl)-(1→2)-α-l-arabinopyranoside-30-alolean-12-en-28-oate (2), named atriplexogenin I, ß-d-glucopyranosyl-3- O-(2- O-sulfo-ß-d-galactopyranosyl)-(1→2)-α-l-arabinopyranoside)-30-hydroxyolean-12-en-28-oate (3), named atriplexogenin II, and ß-d-glucopyranosyl-3 -O-(ß-d-glucopyranosyl-(1→2)-ß-d-galactopyranosyl-(1→2)-α-l-arabinopyranoside)-30-alolean-12-en-28-oate (4), named atriplexogenin III, were isolated by silica gel column and semipreparative HPLC chromatography from the n-butanol extract of the salt marsh plant Atriplex tatarica. In addition, two known secondary metabolites, patuletin3 -O-ß-d-apiofuranosyl-(1‴→2″)-ß-d-glucopyranoside (5) and patuletin 3 -O-5‴- O-feruloyl-ß-d-apiofuranosyl-(1‴→2″)-ß-d-glucopyranoside (6), were isolated for the first time from A. tatarica. The structures of the isolated compounds were elucidated by 1D and 2D NMR, HRESIMS, IR, and UV data. Antibacterial activity by the microdilution method and antibiofilm activity against P. aeruginosa were assessed. Compound 5 possesses significant antibacterial activity, while the most potent antibiofilm agent is compound 2.

Volatile Composition, Colour, and Sensory Quality of Spirit-Based Beverages Enriched with Medicinal Fungus Ganoderma lucidum and Herbal Extract.

The multicomponent mixtures consisting of herbs and fungi are commonly used for the production of alcoholic beverages with potential health-promoting effects in many Asian countries. The medicinal fungus Ganoderma lucidum is one of the most important fungi used for spirit production. Although this fungus affects the aromatic complexity of spirits, only a small number of studies have focused on investigating the influence of G. lucidum on the aromatic profile and colour of spirits. The aim of the research is to evaluate the influence of adding G. lucidum and herbal extract on final concentrations of volatile compounds and sensory quality of several distillates. In this study, distillates (grain, plum, grape and wine) were used to produce new spirit-based beverages with the fungus G. lucidum only, or with the fungus and herbal extract. Fifty-nine aroma compounds were identified by GC-MS. The aromatic profiles were strongly influenced by the primary aromas of the distillates, but the addition of G. lucidum and herbal extract enriched the volatile fraction of distillates with a range of ethyl esters, with a fruity and floral fragrance. Higher alcohols, 1-propanol, 2-isobutanol and isoamyl alcohol, were the most abundant volatile compounds in the analyzed distillates and spirits. The lightness of distillates was from 60.7 to 63.6, and with the addition of Ganoderma it significantly decreased to the range from 43.6 to 50.5. The addition of the fungus also increased the intensity of red and yellow colours. The Ganoderma spirits scored very highly in sensory evaluation (17.6-18.3), significantly better than the spirits without any additions (16.1-16.9).

Short communication: Cheese supplemented with Thymus algeriensis oil, a potential natural food preservative.

The essential oil of Thymus algeriensis was analyzed as a potential preservative in soft cheese. We developed a novel method to test the preserving properties of essential oil in soft cheese. Contamination incidence of Penicillium aurantiogriseum was absent after 30 d of storage at 4°C with 25 µL of essential oil added. The antimicrobial activity was tested against 8 bacteria and 8 fungi. Thymus algeriensis oil showed inhibitory activity against tested bacteria at 0.03 to 0.09 mg/mL, and bactericidal activity was achieved at 0.05 to 0.15 mg/mL. For antifungal activity, minimum inhibitory concentrations ranged between 0.01 and 0.04 mg/mL and minimum fungicidal concentrations between 0.01 and 0.04 mg/mL. Furthermore, the oil was also screened for antiradical activity using the 1,1-diphenyl-2-picrylhydrazyl assay. The results showed that the oil was active and achieved half-maximal inhibitory activity at 0.132 mg/mL. We used gas chromatography, gas chromatography-mass spectrometry, and nuclear magnetic resonance spectrometry to investigate the volatile compounds from the oil. Carvacrol was identified as the main compound in the oil, represented by 80.9% of the total constituents, followed by p-cymene (7.7%).

Chemotaxonomic Considerations of the n-Alkane Composition in Pinus heldreichii, P. nigra, and P. peuce.

The n-alkane composition in the leaf cuticular waxes of natural populations of Bosnian pine (Pinus heldreichii), Austrian pine (P. nigra), and Macedonian pine (P. peuce) was compared for the first time. The range of n-alkanes was wider in P. nigra (C16  - C33 ) than in P. heldreichii and P. peuce (C18  - C33 ). Species also diverged in abundance and range of dominant n-alkanes (P. heldreichii: C23 , C27 , and C25 ; P. nigra: C25 , C27 , C29 , and C23 ; P. peuce: C29 , C25 , C27 , and C23 ). Multivariate statistical analyses (PCA, DA, and CA) generally pointed out separation of populations of P. nigra from populations of P. heldreichii and P. peuce (which were, to a greater or lesser extent, separated too). However, position of these species on the basis of n-alkane composition was in accordance neither with infrageneric classification nor with recent molecular and terpene investigations.

Neuroprotective Potential and Chemical Profile of Alternatively Cultivated Ganoderma lucidum Basidiocarps.

Various neurodegenerative diseases are the main challenges to the modern medicine and there is a great need for novel, natural, neuroprotective agents. Ganoderma lucidum is a well-known medicinal mushroom, which health benefits have been confirmed by numerous studies. As demand for its basidiocarps is increased and traditional cultivation on hardwoods is not environmentally friendly and economically justified, finding of alternative substrates is necessary. The aim of the study was to assess the effect of alternative cultivation substrates on the chemical profile of G. lucidum basidiocarps and their capacity to inhibit acetylcholinesterase and tyrosinase, which higher activity is directly associated with neurodegenerative processes. Extracts of basidiocarps cultivated on alternative substrates, especially on clear wheat straw, showed significantly higher inhibition capacities than extracts of commercially-grown ones. These extracts were considerably different chemically from commercial basidiocarps extracts and even nine new compounds were isolated from them. Our results suggest that cultivation substrate greatly affect the chemical profile and neuroprotective capacity of obtained basidiocarps and wheat straw is a promising cultivation substrate.

Antioxidant Activity of Selected Polyphenolics in Yeast Cells: The Case Study of Montenegrin Merlot Wine.

Screens of antioxidant activity (AA) of various natural products have been a focus of the research community worldwide. This work aimed to differentiate selected samples of Merlot wines originated from Montenegro, with regard to phenolic profile and antioxidant capacity studied by survival rate, total sulfhydryl groups and activities of glutathione peroxidase (GPx), glutathione reductase and catalase in H2O2⁻stressed Saccharomyces cerevisiae cells. In this study, DPPH assay was also performed. Higher total phenolic content leads to an enhanced AA under both conditions. The same trend was observed for catechin and gallic acid, the most abundant phenolics in the examined wine samples. Finally, the findings of an Artificial Neural Network (ANN) model were in a good agreement (r² = 0.978) with the experimental data. All tested samples exhibited a protective effect in H2O2⁻stressed yeast cells. Pre-treatment with examined wines increased survival in H2O2⁻stressed cells and shifted antioxidative defense towards GPx⁻mediated defense. Finally, sensitivity analysis of obtained ANN model highlights the complexity of the impact that variations in the concentrations of specific phenolic components have on the antioxidant defense system.

Antifungal activity of the pygidial gland secretion of Laemostenus punctatus (Coleoptera: Carabidae) against cave-dwelling micromycetes.

The antifungal potential of the pygidial gland secretion of the troglophilic ground beetle Laemostenus punctatus from a cave in Southeastern Serbia against cave-dwelling micromycetes, isolated from the same habitat, has been investigated. Eleven collected samples were analyzed and 32 isolates of cave-dwelling fungi were documented. A total of 14 fungal species were identified as members of the genera Aspergillus, Penicillium, Alternaria, Cladosporium, Rhizopus, Trichoderma, Arthrinium, Aureobasidium, Epicoccum, Talaromyces, and Fusarium. Five isolates were selected for testing the antifungal activity of the pygidial gland secretion: Talaromyces duclauxi, Aspergillus brunneouniseriatus, Penicillium sp., Rhizopus stolonifer, and Trichoderma viride. The microdilution method has been applied to detect minimal inhibitory concentrations (MICs) and minimal fungicidal concentrations (MFCs). The most sensitive isolate was Penicillium sp., while the other isolates demonstrated a high level of resistance to the tested agent. L. punctatus has developed a special mechanism of producing specific compounds that act synergistically within the secretion mixture, which are responsible for the antifungal action against pathogens from the cave. The results open opportunities for further research in the field of ground beetle defense against pathogens, which could have an important application in human medicine, in addition to the environmental impact, primarily.

Bioactive Pentacyclic Triterpene Ester Derivatives from Alnus viridis ssp. viridis Bark.

Seven derivatives of pentacyclic triterpene acids (1-7) were isolated from the bark of Alnus viridis ssp. viridis using a combination of column chromatography and semipreparative HPLC. Compounds 1-3, 6, and 7 were determined to be new after spectroscopic data interpretation and were assigned as 27-hydroxyalphitolic acid derivatives (1-3), a 27-hydroxybetulinic acid derivative (6), and a 3-epi-maslinic acid derivative (7), respectively. Pentacyclic triterpenoids with a C-27 hydroxymethyl group have been found in species of the genus Alnus for the first time. These compounds were subjected to cytotoxicity testing against a number of cancer cell lines. Also, selected pentacyclic triterpenoids were selected as potential inhibitors of topoisomerases I and IIα for an in silico investigation.

The pygidial gland secretion of the forest caterpillar hunter, Calosoma (Calosoma) sycophanta: the antimicrobial properties against human pathogens.

Recently, various insect secretions have been tested as possible antimicrobial agents. In beetles, these secretions are essentially products of various exocrine glands, of which particular emphasis is on pygidial glands that are common for the suborder Adephaga. The antimicrobial potential of the pygidial gland secretion isolated from the adults of Calosoma sycophanta against human pathogens has been tested and compared with the potential of other carabid species, particularly within the tribe Carabini. The antimicrobial assay includes a microdilution method which was applied in order to determine the minimal inhibitory, minimal fungicidal and minimal bactericidal concentrations. It has been tested the effect of the secretion against eight strains of fungal and eight strains of bacterial species. The secretion sample of the tested carabid species has shown statistically significant antifungal effect against all strains of treated micromycetes, the highest in comparison with previously tested carabids (Carabus spp., Laemostenus punctatus and Abax parallelepipedus). Aspergillus versicolor proved to be the most sensitive micromycete, while the remaining seven fungal strains have shown the same level of sensibility. In comparison with commercial mycotics ketoconazole and bifonazole, applied as positive controls, the tested secretion showed much higher antifungal activity for all fungal strains. Antibacterial effect has been manifested only against one bacterial strain (Escherichia coli), contrary to other previously studied carabid species. These observations might have a significant impact on the ecological domain and possible purpose in biomedical studies and applications in the future. Additionally, morpho-histology of the pygidial glands of C. sycophanta is investigated and discussed.

Qualitative HPLC-DAD/ESI-TOF-MS Analysis, Cytotoxic, and Apoptotic Effects of Croatian Endemic Centaurea ragusina L. Aqueous Extracts.

Centaurea ragusina L., an endemic Croatian plant species, revealed a good cytotoxic activity of aqueous extracts (AE) on human bladder (T24) and human glioblastoma (A1235) cancer cell lines. The chemical constituents were tentatively identified using high performance liquid chromatography HPLC-DAD/ESI-TOF-MS in negative ionization mode. The main compounds of herba extract were sesquiterpene lactones: solstitialin A 3,13-diacetate and epoxyrepdiolide; organic acid: quinic acid. The main compounds of flower extract were organic acids: quinic acid, citric acid, and malic acid; sesquiterpene lactone: cynaropicrin; phenolic compounds: chlorogenic acid and phenylpropanoid: syringin. The AE of C. ragusina were investigated for correlation of their effects on human bladder (T24) and human glioblastoma (A1235) cancer cell lines using the MTT assay. Although both extracts showed significant dose- and time-dependent cytotoxic activity against both cancer cell lines, the flower extract exhibited slightly higher activity. In order to determine type of cell death induced by treatment, cell lines were exposed subsequently to a treatment with both flower and herba AE. The majority of the cells died by induced apoptosis treatment. Flower AE (26.25%), compared to a leaf AE (22.15%) showed slightly higher percentage of an apoptosis in T24 cells, when compared to a non-treated cells (0.04%).

Chemodiversity of Epicuticular n-Alkanes and Morphological Traits of Natural Populations of Satureja subspicata Bartl. ex Vis. along Dinaric Alps - Ecological and Taxonomic Aspects.

Morphological characters and the composition of epicuticular leaf n-alkanes of two Satureja subspicata Bartl. ex Vis. subspecies (subsp. liburnica Silic and subsp. subspicata) from nine natural populations along Dinaric Alps range were studied. Morphological characters were chosen based on Silic's subspecies separation. Seventeen n-alkane homologues (C19 - C35 ) were identified using gas chromatography/mass spectrometry (GC/MS) and GC/flame ionisation detector (FID). The most abundant n-alkane in all populations was n-nonacosane (C29 ), followed by n-hentriacontane (C31 ), with the exception of Divaca population where these two alkanes were co-dominant. Diversity and variability of n-alkane patterns and morphological characters and their relation to different geographic and bioclimatic parameters, including exposure, were analysed by several statistical multivariate methods (PCA, HCA, Discriminant Analysis, Mantel test). These tests showed clear separation of subsp. liburnica from subsp. subspicata, even though population Velebit showed separation from other subsp. liburnica populations based on phytochemical characters. Mantel test showed high correlation with geographical distribution in both investigated data sets. High correlation between morphological and phytochemical characters was also established. However, exposure can influence n-alkane profile, suggesting precaution while taking samples from natural habitats.

Terpenes as Useful Markers in Differentiation of Natural Populations of Relict Pines Pinus heldreichii, P. nigra, and P. peuce.

Comparative analysis of terpene diversity and differentiation of relict pines Pinus heldreichii, P. nigra, and P. peuce from the central Balkans was performed at the population level. Multivariate statistical analyses showed that the composition of needle terpenes reflects clear divergence among the pine species from different subgenera: P. peuce (subgenus Strobus) vs. P. nigra and P. heldreichii (subgenus Pinus). In addition, despite the described morphological similarities and the fact that P. nigra and P. heldreichii may spontaneously hybridize, our results indicated differentiation of their populations naturally growing in the same area. In accordance with recently proposed concept of 'flavonic evolution' in the genus Pinus, we assumed that the terpene profile of soft pine P. peuce, defined by high amounts of six monoterpenes, is more basal than those of hard pines P. nigra and P. heldreichii, which were characterized by high content levels of mainly sesquiterpenes. In order to establish precise positions of P. heldreichii, P. nigra and P. peuce within the taxonomic and phylogenetic tree, as well as develop suitable conservation strategies and future breeding efforts, it is necessary to perform additional morphological, biochemical, and genetic studies.

Antimicrobial activity of the pygidial gland secretion of three ground beetle species (Insecta: Coleoptera: Carabidae).

The antimicrobial properties of the pygidial gland secretions released by the adults of the three ground beetle species, Carabus ullrichii, C. coriaceus, and Abax parallelepipedus, have been tested. Microdilution method was applied for detection of minimal inhibitory concentrations (MICs), minimal bactericidal concentrations (MBCs), and minimal fungicidal concentrations (MFCs). Additionally, morpho-histology of the pygidial glands is investigated. We have tested 16 laboratory and clinical strains of human pathogens--eight bacterial both gram-positive and gram-negative species and eight fungal species. The pygidial secretion samples of C. ullrichii have showed the strongest antimicrobial effect against all strains of treated bacteria and fungi. Staphylococcus aureus, Lysteria monocytogenes, and Salmonella typhimurium proved to be the most sensitive bacterial strains. Penicillium funiculosum proved to be the most sensitive micromycete, while P. ochrochloron and P. verrucosum var. cyclopium the most resistant micromycetes. The pygidial secretion of C. coriaceus has showed antibacterial potential solely against Pseudomonas aeruginosa and antifungal activity against Aspergillus fumigatus, A. versicolor, A. ochraceus, and P. ochrochloron. Antibacterial properties of pygidial gland secretion of A. parallelepipedus were achieved against P. aeruginosa, while antifungal activity was detected against five of the eight tested micromycetes (A. fumigatus, A. versicolor, A. ochraceus, Trichoderma viride, and P. verrucosum var. cyclopium). Commercial antibiotics Streptomycin and Ampicillin and mycotics Ketoconazole and Bifonazole, applied as the positive controls, showed higher antibacterial/antifungal properties for all bacterial and fungal strains. The results of this observation might have a significant impact on the environmental aspects and possible medical purpose in the future.

Essential-oil variability of Juniperus deltoides R.P.Adams along the east Adriatic coast - how many chemotypes are there?

The composition of the essential oils isolated from twigs of ten Juniperus deltoides R.P. Adams populations from the east Adriatic coast was determined by GC-FID and GC/MS analyses. Altogether, 169 compounds were identified, representing 95.6-98.4% of the total oil composition. The oils were dominated by monoterpenes (average content of 61.6%), which are characteristic oil components of species of the Juniperus section. Two monoterpenes, α-pinene and limonene, were the dominant constituents, comprising on average 46.78% of the essential oils. Statistical methods were deployed to determine the diversity of the terpene classes and the common terpenes between the investigated populations. These statistical analyses revealed the existence of three chemotypes within all populations, i.e., a α-pinene, limonene, and limonene/α-pinene type.

Composition of leaf n-alkanes in three Satureja montana L. subspecies from the Balkan peninsula: ecological and taxonomic aspects.

The composition of the epicuticular leaf n-alkanes of eight populations of three Satureja montana subspecies (S. montana L. subsp. pisidica (Wettst.) Silic, S. montana L. subsp. montana, and S. montana L. subsp. variegata (Host) P. W. Ball), from central and western areas of the Balkan Peninsula was characterized by GC-FID and GC/MS analyses. In the leaf waxes, 15 n-alkane homologs with chain-lengths ranging from C21 to C35 were identified. The main n-alkane in almost all samples was n-nonacosane (C29 ), but differences in the contents of three other dominant n-alkanes allowed separating the coastal from the continental populations. The diversity and variability of the epicuticular-leaf-n-alkane patterns and their relation to different geographic and bioclimatic parameters were analyzed by several statistical methods (principal component, discriminant, and cluster analyses as well as the Mantel test). All tests showed a high correlation between the leaf n-alkane pattern and the geographical distribution of the investigated populations, confirming the differentiation between S. montana subsp. pisidica and the other two subspecies. The S. montana subsp. variegata and S. montana subsp. montana populations are geographically closer and their differentiation according to the leaf-n-alkane patterns was not clear, even though there was some indication of discrimination between them. Moreover, most of the bioclimatic parameters related to temperature were highly correlated with the differentiation of the coastal and the continental populations.

Synthesis of novel tetrahydrobenzazepine derivatives and their cytoprotective effect on human lymphocytes.

Cytoprotective compounds such as amifostine play an important role in chemo- and radiotherapy due to their ability to reduce the side effects of these treatments. Our work was initiated with the intention to design, synthesise and test a new class of heterocyclic compounds that would have an antioxidative profile with the potential to be further developed as cytoprotective agents. The design was based on the privileged tetrahydrobenzazepine scaffold found in many natural products with a wide range of biological properties. This structure was further functionalised with moieties known to possess antioxidative features such as tertiary amine and styrene double bond. A series of eight tetrahydrobenzazepine derivatives of isoquinoline, 3,4-dihydro-ß-carboline and pyridine were synthesised employing the Heck reaction as a key transformation. Some of the prepared compounds were tested for their in vitro effects on chromosome aberrations in peripheral human lymphocytes using the cytochalasin-B blocked micronucleus (MN) assay. Three tetrahydrobenzoazepine derivatives showed significant cytoprotective properties, comparable or even better to those of the radioprotective agent amifostine.