Polyamines participate in the processes of cell growth and development. The degradation branch of their metabolism involves amine oxidases. The oxidation of spermine, spermidine and putrescine releases hydrogen peroxide and the corresponding aminoaldehyde. Polyamine-derived aminoaldehydes have been found to be cytotoxic, and they represent the subject of this review. 3-aminopropanal disrupts the lysosomal membrane and triggers apoptosis or necrosis in the damaged cells. It is implicated in the pathogenesis of cerebral ischemia. Furthermore, 3-aminopropanal yields acrolein through the elimination of ammonia. This reactive aldehyde is also generated by the decomposition of aminoaldehydes produced in the reaction of serum amine oxidase with spermidine or spermine. In addition, acrolein is a common environmental pollutant. It causes covalent modifications of proteins, including carbonylation, the production of Michael-type adducts and cross-linking, and it has been associated with inflammation-related diseases. APAL and acrolein are detoxified by aldehyde dehydrogenases and other mechanisms. High-performance liquid chromatography, immunochemistry and mass spectrometry have been largely used to analyze the presence of polyamine-derived aminoaldehydes and protein modifications elicited by their effect. However, the main and still open challenge is to find clues for discovering clear linkages between aldehyde-induced modifications of specific proteins and the development of various diseases.

• Klíčová slova
• 3-aminopropanal, Michael adduct, Schiff base, acrolein, aldehyde dehydrogenase, amine oxidase, aminoaldehyde, cytotoxicity, glutathione, protein modification,
• MeSH
• akrolein * farmakologie   MeSH
• aldehydy farmakologie   MeSH
• polyaminy * MeSH
• spermidin farmakologie   MeSH
• spermin farmakologie   MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• 3-aminopropionaldehyde MeSH Prohlížeč
• akrolein * MeSH
• aldehydy MeSH
• polyaminy * MeSH
• spermidin MeSH
• spermin MeSH

Background: Increasing resistance has resulted in an urgent need for new antimicrobial drugs. A systematic me-too approach was chosen to modify clinically used sulfonamides to obtain their imines. Methods & results: Twenty-five compounds were synthesized and evaluated for their antibacterial activity. The most active compounds were also investigated against methicillin- and trimethoprim/sulfamethoxazole (SMX)-resistant Gram-positive species. Staphylococci shared the highest susceptibility including resistant strains with minimum inhibitory concentrations from 3.91 μM (≥2.39 μg ml-1). Crucially, the compounds inhibit MRSA and trimethoprim/SMX-resistant Staphylococci without any cross-resistance. Modification of parent sulfonamides turned a bacteriostatic effect into a bactericidal effect. Toxicity for HepG2 and hemolytic properties were also determined. Conclusions: The presence of a dihalogenated salicylidene moiety is required for optimal activity. Based on toxicity, promising derivatives for further investigation were identified.

• Klíčová slova
• Schiff bases, Staphylococcus aureus, antibacterial activity, cytotoxicity, drug resistance, imine, in vitro activity, sulfamethoxazole, sulfonamides,
• MeSH
• aldehydy chemie   farmakologie   MeSH
• antibakteriální látky chemická syntéza   chemie   farmakologie   MeSH
• bakteriální léková rezistence účinky léků   MeSH
• iminy chemie   farmakologie   MeSH
• mikrobiální testy citlivosti MeSH
• molekulární struktura MeSH
• Staphylococcus účinky léků   MeSH
• sulfonamidy chemie   farmakologie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aldehydy MeSH
• antibakteriální látky MeSH
• iminy MeSH
• salicylaldehyde MeSH Prohlížeč
• sulfonamidy MeSH

The comparative study of new proteasome inhibitors based on salicylic acid-modified pseudo-tripeptides terminated with aldehyde or vinylsulfone is presented. We described the synthesis of 11 pairs of pseudopeptides and their properties related to the proteasome inhibition were determined. The effects of integrated amino acids (combinations of leucine, phenylalanine, tryptophan, proline, cyclohexylalanine or norleucine residues) on the activity of the proteasome were investigated. Compounds preferentially inhibited the chymotrypsin β5-subunit of the proteasome in cell-based assays compared with the β1- and β2-subunits, with IC50 values in mid-nanomolar ranges being obtained for the most active members. Our comparative study demonstrated that aldehydes were able to inhibit the proteasome in cells more effectively than vinylsulfones. These results were corroborated by the accumulation of polyubiquitinated proteins in treated cells, GFP accumulation in a reporter cell line and the ability of new compounds to induce apoptotic cell death.

• Klíčová slova
• Apoptosis, Inhibitor, Proteasome, Salicylamide, Ubiquitin,
• MeSH
• aldehydy chemie   farmakologie   MeSH
• inhibitory proteasomu chemická syntéza   chemie   farmakologie   MeSH
• lidé MeSH
• molekulární struktura MeSH
• nádorové buněčné linie MeSH
• peptidy chemie   farmakologie   MeSH
• proteasomový endopeptidasový komplex metabolismus   MeSH
• sulfony chemie   farmakologie   MeSH
• vinylové sloučeniny chemie   farmakologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aldehydy MeSH
• inhibitory proteasomu MeSH
• peptidy MeSH
• proteasomový endopeptidasový komplex MeSH
• sulfony MeSH
• vinylové sloučeniny MeSH

Aza-peptide aldehydes and ketones are a new class of reversible protease inhibitors that are specific for the proteasome and clan CD cysteine proteases. We designed and synthesised aza-Leu derivatives that were specific for the chymotrypsin-like active site of the proteasome, aza-Asp derivatives that were effective inhibitors of caspases-3 and -6, and aza-Asn derivatives that inhibited S. mansoni and I. ricinus legumains. The crystal structure of caspase-3 in complex with our caspase-specific aza-peptide methyl ketone inhibitor with an aza-Asp residue at P1 revealed a covalent linkage between the inhibitor carbonyl carbon and the active site cysteinyl sulphur. Aza-peptide aldehydes and ketones showed no cross-reactivity towards cathepsin B or chymotrypsin. The initial in vitro selectivity of these inhibitors makes them suitable candidates for further development into therapeutic agents to potentially treat multiple myeloma, neurodegenerative diseases, and parasitic infections.

• Klíčová slova
• Proteasome inhibitor, anticancer, antiparasitic, aza-peptide carbonyls, caspase and legumain inhibitors,
• MeSH
• aldehydy chemie   farmakologie   MeSH
• aza sloučeniny chemie   farmakologie   MeSH
• cysteinové endopeptidasy metabolismus   MeSH
• inhibitory proteas chemická syntéza   chemie   farmakologie   MeSH
• ketony chemie   farmakologie   MeSH
• krystalografie rentgenová MeSH
• lidé MeSH
• molekulární modely MeSH
• molekulární struktura MeSH
• peptidy chemie   farmakologie   MeSH
• proteasomový endopeptidasový komplex metabolismus   MeSH
• racionální návrh léčiv * MeSH
• skot MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• skot MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aldehydy MeSH
• aza sloučeniny MeSH
• cysteinové endopeptidasy MeSH
• inhibitory proteas MeSH
• ketony MeSH
• peptidy MeSH
• proteasomový endopeptidasový komplex MeSH

Due to their enhanced reactivity, metal and metal-oxide nanoscale zero-valent iron (nZVI) nanomaterials have been introduced into remediation practice. To ensure that environmental applications of nanomaterials are safe, their possible toxic effects should be described. However, there is still a lack of suitable toxicity tests that address the specific mode of action of nanoparticles, especially for nZVI. This contribution presents a novel approach for monitoring one of the most discussed adverse effects of nanoparticles, i.e., oxidative stress (OS). We optimized and developed an assay based on headspace-SPME-GC-MS analysis that enables the direct determination of volatile oxidative damage products (aldehydes) of lipids and proteins in microbial cultures after exposure to commercial types of nZVI. The method employs PDMS/DVB SPME fibers and pentafluorobenzyl derivatization, and the protocol was successfully tested using representatives of bacteria, fungi, and algae. Six aldehydes, namely, formaldehyde, acrolein, methional, benzaldehyde, glyoxal, and methylglyoxal, were detected in the cultures, and all of them exhibited dose-dependent sigmoidal responses. The presence of methional, which was detected in all cultures except those including an algal strain, documents that nZVI also caused oxidative damage to proteins in addition to lipids. The most sensitive toward nZVI exposure in terms of aldehyde production was the yeast strain Saccharomyces cerevisiae, which had an EC50 value of 0.08 g/L nZVI. To the best of our knowledge, this paper is the first to document the production of aldehydes resulting from lipids and proteins as a result of OS in microorganisms from different kingdoms after exposure to iron nanoparticles.

• Klíčová slova
• Nanomaterial, Oxidative stress, Remediation, SPME, Toxicity assay, Yeast,
• MeSH
• aldehydy farmakologie   MeSH
• Bacteria účinky léků   MeSH
• kovové nanočástice toxicita   MeSH
• lipidy MeSH
• nanostruktury MeSH
• oxidace-redukce MeSH
• oxidační stres fyziologie   MeSH
• testy toxicity MeSH
• železité sloučeniny MeSH
• železo metabolismus   toxicita   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aldehydy MeSH
• ferric oxide MeSH Prohlížeč
• lipidy MeSH
• methional MeSH Prohlížeč
• železité sloučeniny MeSH
• železo MeSH

Salicylaldehyde isonicotinoyl hydrazone (SIH) is a small molecule and lipophilic chelating agent that firmly binds ferric ions from the cellular labile iron pool and is able to protect various tissues against oxidative damage. Previously, SIH possessed the best ratio of cytoprotective efficiency to toxicity among various iron chelators, including the desferrioxamine, deferiprone, and deferasirox used in clinical practice. Here, we prepared a series of 2,6-dihydroxybenzaldehyde aroylhydrazones as SIH analogues with an additional hydroxyl group that can be involved in the chelation of metal ions. Compound JK-31 (2,6-dihydroxybenzaldehyde 4-chlorobenzohydrazone) showed the best cytoprotective efficiency among the studied compounds including SIH. This compound significantly protected H9c2 cardiomyoblast cells against oxidative stress induced by various pro-oxidants, such as hydrogen peroxide, tert-butyl hydroperoxide, paraquat, epinephrine, N-acetyl- p-benzoquinone imine (a toxic metabolite of paracetamol), and 6-hydroxydopamine. The exceptional cytoprotective activity of JK-31 was confirmed using epifluorescence microscopy, where JK-31-treated H9c2 cells maintained a higher mitochondrial inner membrane potential in the presence of a lethal dose of hydrogen peroxide than was observed with cells treated with SIH. Hence, this study demonstrates the deleterious role of free iron ions in oxidative injury and the potential of 2,6-dihydroxybenzaldehyde aroylhydrazones in the prevention of various types of cardiac injuries, highlighting the need for further investigations into these compounds.

• MeSH
• aldehydy chemie   farmakologie   MeSH
• benzaldehydy chemie   MeSH
• buněčné linie MeSH
• chelátory železa chemie   farmakologie   MeSH
• hydrazony chemie   farmakologie   MeSH
• hydrolýza MeSH
• kardiomyocyty cytologie   účinky léků   metabolismus   MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• membránový potenciál mitochondrií účinky léků   MeSH
• ochranné látky chemie   farmakologie   MeSH
• oxidační stres * účinky léků   MeSH
• proliferace buněk účinky léků   MeSH
• stabilita léku MeSH
• viabilita buněk účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aldehydy MeSH
• benzaldehyde MeSH Prohlížeč
• benzaldehydy MeSH
• chelátory železa MeSH
• hydrazony MeSH
• ochranné látky MeSH
• salicylaldehyde isonicotinoyl hydrazone MeSH Prohlížeč

The resistance among microbes has brought an urgent need for new drugs. Thus, we synthesized a series of Schiff bases derived from the sulfa drug sulfadiazine and various salicylaldehydes. The resulting 4-[(2-hydroxybenzylidene)amino]-N-(pyrimidin-2-yl)benzene-sulfonamides were characterized and evaluated against Gram-positive and Gram-negative bacteria, yeasts, moulds, Mycobacterium tuberculosis, nontuberculous mycobacteria (M. kansasii, M. avium) and their cytotoxicity was determined. Among bacteria, the genus Staphylococcus, including methicillin-resistant S. aureus, showed the highest susceptibility, with minimum inhibitory concentration values from 7.81 µM. The growth of Candida sp. and Trichophyton interdigitale was inhibited at concentrations starting from 1.95 µM. 4-[(2,5-Dihydroxybenzylidene)amino]-N-(pyrimidin-2-yl)-benzenesulfonamide was identified as the most selective Schiff base for these strains with no apparent cytotoxicity and a selectivity index higher than 16. With respect to M. tuberculosis and M. kansasii that were inhibited within the range of 8 to 250 µM, unsubstituted 4-[(2-hydroxy-benzylidene)amino]-N-(pyrimidin-2-yl)benzenesulfonamide meets the selectivity requirement. In general, dihalogenation of the salicylic moiety improved the antibacterial and antifungal activity but also increased the cytotoxicity, especially with an increasing atomic mass. Some derivatives offer more advantageous properties than the parent sulfadiazine, thus constituting promising hits for further antimicrobial drug development.

• Klíčová slova
• Schiff bases, antibacterial activity, antifungal activity, antimycobacterial activity, cytotoxicity, sulfadiazine, sulfonamides,
• MeSH
• aldehydy chemická syntéza   farmakologie   MeSH
• antibakteriální látky chemická syntéza   chemie   farmakologie   MeSH
• antifungální látky chemická syntéza   chemie   farmakologie   MeSH
• antiinfekční látky chemická syntéza   farmakologie   MeSH
• buňky Hep G2 MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• pyrimidiny chemická syntéza   farmakologie   MeSH
• Schiffovy báze chemická syntéza   farmakologie   MeSH
• sulfadiazin analogy a deriváty   chemická syntéza   farmakologie   MeSH
• viabilita buněk účinky léků   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aldehydy MeSH
• antibakteriální látky MeSH
• antifungální látky MeSH
• antiinfekční látky MeSH
• pyrimidiny MeSH
• salicylaldehyde MeSH Prohlížeč
• Schiffovy báze MeSH
• sulfadiazin MeSH

Free cellular iron catalyzes the formation of toxic hydroxyl radicals and therefore chelation of iron could be a promising therapeutic approach in pathological states associated with oxidative stress. Salicylaldehyde isonicotinoyl hydrazone (SIH) is a strong intracellular iron chelator with well documented potential to protect against oxidative damage both in vitro and in vivo. Due to the short biological half-life of SIH and risk of toxicity due to iron depletion, boronate prochelator BSIH has been designed. BSIH cannot bind iron until it is activated by certain reactive oxygen species to active chelator SIH. The aim of this study was to examine the toxicity and cytoprotective potential of BSIH, SIH, and their decomposition products against hydrogen peroxide-induced injury of H9c2 cardiomyoblast cells. Using HPLC, we observed that salicylaldehyde was the main decomposition products of SIH and BSIH, although a small amount of salicylic acid was also detected. In the case of BSIH, the concentration of formed salicylaldehyde consistently exceeded that of SIH. Isoniazid and salicylic acid were not toxic nor did they provide any antioxidant protective effect in H9c2 cells. In contrast, salicylaldehyde was able to chelate intracellular iron and significantly preserve cellular viability and mitochondrial inner membrane potential induced by hydrogen peroxide. However it was consistently less effective than SIH. The inherent toxicities of salicylaldehyde and SIH were similar. Hence, although SIH - the active chelating agent formed following the BSIH activation - undergoes rapid hydrolysis, its principal decomposition product salicylaldehyde accounts markedly for both cytoprotective and toxic properties.

• Klíčová slova
• Boronyl salicylaldehyde isonicotinoyl hydrazone (BSIH), Iron chelation, Prochelator, Salicylaldehyde, Salicylaldehyde isonicotinoyl hydrazone (SIH),
• MeSH
• aldehydy farmakologie   toxicita   MeSH
• buněčné linie MeSH
• chelátory železa farmakologie   toxicita   MeSH
• hydrazony farmakologie   toxicita   MeSH
• krysa rodu Rattus MeSH
• kyseliny boronové farmakologie   toxicita   MeSH
• kyseliny isonikotinové farmakologie   toxicita   MeSH
• membránový potenciál mitochondrií účinky léků   MeSH
• myoblasty srdeční účinky léků   metabolismus   MeSH
• oxidační stres účinky léků   MeSH
• peroxid vodíku toxicita   MeSH
• poločas MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• viabilita buněk účinky léků   MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• železo metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• (isonicotinic acid (2-(4,4,5,5-tetramethyl-(1,3,2)dioxaborolan-2-yl)benzylidene)hydrazide) MeSH Prohlížeč
• aldehydy MeSH
• chelátory železa MeSH
• hydrazony MeSH
• kyseliny boronové MeSH
• kyseliny isonikotinové MeSH
• peroxid vodíku MeSH
• reaktivní formy kyslíku MeSH
• salicylaldehyde isonicotinoyl hydrazone MeSH Prohlížeč
• železo MeSH

The chemical defence of Heteroptera is primarily based on repellent secretions which signal the potential toxicity of the bug to its predators. We tested the aversive reactions of green lizards (Lacerta viridis) towards the major compounds of the defensive secretion of Graphosoma lineatum, specifically: (i) a mixture of three aldehydes: (E)-hex-2-enal, (E)-oct-2-enal, (E)-dec-2-enal; (ii) a mixture of these three aldehydes and tridecane; (iii) oxoaldehyde: (E)-4-oxohex-2-enal; (iv) secretion extracted from metathoracic scent glands of G. lineatum adults and (v) hexane as a non-polar solvent. All chemicals were presented on a palatable food (Tenebrio molitor larvae). The aversive reactions of the green lizards towards the mealworms were evaluated by observing the approach latencies, attack latencies and approach-attack intervals. The green lizards exhibited a strong aversive reaction to the mixture of three aldehydes. Tridecane reduced the aversive reaction to the aldehyde mixture. Oxoaldehyde caused the weakest, but still significant, aversive reaction. The secretion from whole metathoracic scent glands also clearly had an aversive effect on the green lizards. Moreover, when a living specimen of G. lineatum or Pyrrhocoris apterus (another aposematic red-and-black prey) was presented to the green lizards before the trials with the aldehyde mixture, the aversive effect of the mixture was enhanced. In conclusion, the mixture of three aldehydes had the strong aversive effect and could signal the potential toxicity of G. lineatum to the green lizards.

• Klíčová slova
• Aposematism, Aversive reaction, Chemical defence, Graphosoma lineatum, Repellent secretion,
• MeSH
• aldehydy izolace a purifikace   farmakologie   MeSH
• Heteroptera chemie   MeSH
• ještěři fyziologie   MeSH
• pachové žlázy chemie   MeSH
• stravovací zvyklosti účinky léků   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aldehydy MeSH

Salicylaldehyde isonicotinoyl hydrazone (SIH) is a lipophilic, tridentate iron chelator with marked anti-oxidant and modest cytotoxic activity against neoplastic cells. However, it has poor stability in an aqueous environment due to the rapid hydrolysis of its hydrazone bond. In this study, we synthesized a series of new SIH analogs (based on previously described aromatic ketones with improved hydrolytic stability). Their structure-activity relationships were assessed with respect to their stability in plasma, iron chelation efficacy, redox effects and cytotoxic activity against MCF-7 breast adenocarcinoma cells. Furthermore, studies assessed the cytotoxicity of these chelators and their ability to afford protection against hydrogen peroxide-induced oxidative injury in H9c2 cardiomyoblasts. The ligands with a reduced hydrazone bond, or the presence of bulky alkyl substituents near the hydrazone bond, showed severely limited biological activity. The introduction of a bromine substituent increased ligand-induced cytotoxicity to both cancer cells and H9c2 cardiomyoblasts. A similar effect was observed when the phenolic ring was exchanged with pyridine (i.e., changing the ligating site from O, N, O to N, N, O), which led to pro-oxidative effects. In contrast, compounds with long, flexible alkyl chains adjacent to the hydrazone bond exhibited specific cytotoxic effects against MCF-7 breast adenocarcinoma cells and low toxicity against H9c2 cardiomyoblasts. Hence, this study highlights important structure-activity relationships and provides insight into the further development of aroylhydrazone iron chelators with more potent and selective anti-neoplastic effects.

• MeSH
• aldehydy chemie   farmakologie   toxicita   MeSH
• antioxidancia chemie   farmakologie   MeSH
• buněčné linie MeSH
• chelátory železa chemie   farmakologie   MeSH
• hydrazony chemie   farmakologie   toxicita   MeSH
• lidé MeSH
• MFC-7 buňky MeSH
• myoblasty účinky léků   MeSH
• oxidační stres účinky léků   MeSH
• peroxid vodíku toxicita   MeSH
• protinádorové látky chemie   toxicita   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aldehydy MeSH
• antioxidancia MeSH
• chelátory železa MeSH
• hydrazony MeSH
• peroxid vodíku MeSH
• protinádorové látky MeSH
• salicylaldehyde isonicotinoyl hydrazone MeSH Prohlížeč