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A series of tribenzo[g,l,q]-6H-1,4-diazepino[2,3-b]porphyrazines has been synthesized. A temperature-dependent steric effect was applied in the mixed Linstead macrocyclization of phthalonitrile and 5,7-bis(2'-arylethenyl)-6-propyl-6H-1,4-diazepine-2,3-dicarbonitrile to achieve high yield of low-symmetry A 3 B-type Mg(II) tribenzo[g,l,q]-6H-1,4-diazepino[2,3-b]porphyrazinate. The analysis of photophysical and photochemical properties of the obtained complexes showed the anti-Kasha effect: the ultrafast spin changes successfully compete with the IC. TD-DFT calculations showed that the presence of 1,4-diazepine heterocycle in the porphyrazine structure leads to the formation of additional charge-transfer triplet state T 2 . We propose, it could participate in the pumping of T 1x state alongside with T 1y state (these states are degenerate in D 4h symmetry) and, therefore, increase singlet oxygen ( 1 Δ g ) generation. Stable micellar nanoparticles have been obtained based on the tribenzo[g,l,q]-6H-1,4-diazepino[2,3-b]porphyrazine Mg(II) and Zn(II) complexes using polyvinylpyrrolidone. The nanoparticles effectively interact with model biological structures (FBS and brain homogenate), leading to disaggregation of the macrocycles. They also exhibit pronounced phototoxic effects in MCF-7 cells upon red light irradiation. We propose that enhancement in PDT activity could be explained by their increased resistance to aggregation due to the presence of n-propyl substituent directly attached to the C6 position of the 1,4-diazepine moiety. The demonstrated results show the promising potential of tribenzo-6H-1,4-diazepinoporphyrazines as heavy atom-free photosensitizers., (© 2023 American Society for Photobiology.)

Oxidative stress (OS) plays a key role in the development of cardiovascular diseases (CVD) in three major ways: reactive oxygen species (ROS)-induced reduction of nitric oxide (NO) bioavailability, ROS-induced inflammation and ROS-induced mitochondrial dysfunction. Oxidation of lipid molecules under the action of ROS leads to damage to membrane structures, changes the functioning of membrane-bound enzymes, and impairs membrane permeability and stability. An increase in OS results in the occurrence of endothelial dysfunction and drug tolerance, side effects, requiring discontinuation of drugs. All of these are significant problems of cardiotherapy. Therefore, the search for new alternative NO donors continues. The present research was aimed at studying the protective effect of 2-ethyl-3-hydroxy-6-methylpyridinium 2-nitroxysuccinate (NS) on the cardiovascular system on mouse myocardial ischemia (MI) model. The NS hybrid molecule includes a synthetic vitamin B6 analog 2-ethyl-3-hydroxy-6-methylpyridine (an antioxidant) and 2-nitroxysuccinic acid (a source of nitric oxide). Using the electron paramagnetic resonance (EPR) method and biochemical methods, we showed that the pronounced ability of NS to release NO is favorably combines with the capacity to prevent OS due to mechanisms such as suppression of the lipid peroxidation (LPO) process, antiradical activity and inhibition of the mitochondrial membrane-bound monoamine oxidase A (MAO-A). Using histological methods, we established that the administration of NS (10 mg/kg, i.p.) reduces the number of ischemic fibers and protects cardiomyocytes against ischemia injury. Thus, the complex protective effect allows us to consider NS as an alternative NO donor and a candidate for the development of a new pharmaceutical agent for the treatment of CVD., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The effect of a new pyridoxine derivative B6NO on doxorubicin cytotoxicity and Nrf2-dependent cellular processes in vitro was studied. Antioxidant B6NO enhances the cytotoxic effect of doxorubicin on tumor cells, which is associated with G2/M cell division arrest and an increase in activity of proapoptotic enzyme caspase-3. The antioxidant promotes intracellular accumulation and nuclear translocation of Nrf2 transcription factor in non-tumor and tumor cells. In non-tumor cells, B6NO increases the expression of antioxidant system proteins and reduces ROS generation in the presence of doxorubicin. In tumor cells, no activation of Nrf2-dependent processes occurs under the action of the antioxidant. Our findings demonstrate the prospect of further studies of pyridoxine derivatives as antioxidants to reduce adverse reactions during chemotherapy., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

Here we report the Friedel-Crafts arylation of chlorofullerenes C60Cl6 and C70Cl8 with thiophene-based methyl esters. While C60Cl6 formed expected Cs-C60R5Cl products, C70Cl8 demonstrated a tendency for both substitution of chlorine atoms and addition of an extra thiophene unit, thus forming Cs-C70R8 and C1-C70R9H compounds. The synthesized water-soluble C60 and C70 fullerene derivatives with thiophene-based addends demonstrated high activity against a broad range of viruses, including human immunodeficiency virus, influenza virus, cytomegalovirus, and herpes simplex virus. The record activity of C70 fullerene derivatives against herpes simplex virus together with low toxicity in mice makes them promising candidates for the development of novel non-nucleoside antiherpetic drugs.

Anti-amyloid activity, aggregation behaviour, cytotoxicity and acute toxicity were investigated for three water-soluble fullerene derivatives with different types of solubilizing addends. All investigated compounds showed a strong anti-amyloid effect in vitrocaused by interaction of the water-soluble fullerene derivatives with the Ab(1-42)-peptide and followed by destruction of the amyloid fibrils. Notably, all of the studied fullerene derivatives showed very low cytotoxicity and low acute toxicity in mice (most promising compound 3 was more than four times less toxic than aspirin). Strong anti-amyloid effect of the fullerene derivatives together with low toxicity reveals high potential of these compounds as drug candidates for treatment of neurodegenerative diseases., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Antioxidant activity of a pharmaceutical substance hypocard was compared with activity of nitromalic acid and well-known agents nicorandil and Mexidol. The ability of these substances to inhibit spontaneous and oxidant-induced LPO process in rat brain homogenate was analyzed. The mechanisms of these effects were studied. The antioxidant properties of hypocard manifested in the inhibition of Fe(II)-induced LPO were significantly more pronounced in comparison with Mexidol and nicorandil.

Background: Anti-tumor effect of hydroxamic acid derivatives is largely connected with its properties as efficient inhibitors of histone deacetylases, and other metalloenzymes involved in carcinogenesis., Objective: The work was aimed to (i) determine the anti-tumor and chemosensitizing activity of the novel racemic spirocyclic hydroxamic acids using experimental drug sensitive leukemia P388 of mice, and (ii) determine the structure-activity relationships as metal chelating and HDAC inhibitory agents., Method: Outbreed male rat of 200-220 g weights were used in biochemical experiments. In vivo experiments were performed using the BDF1 hybrid male mice of 22-24 g weight. Lipid peroxidation, Fe (II) -chelating activity, HDAC fluorescent activity, anti-tumor and anti-metastatic activity, acute toxicity techniques were used in this study., Results: Chemosensitizing properties of water soluble cyclic hydroxamic acids (CHA) are evaluated using in vitro activities and in vivo methods and found significant results. These compounds possess iron (II) chelating properties, and slightly inhibit lipid peroxidation. CHA prepared from triacetonamine (1a-e) are more effective Fe (II) ions cheaters, as compared to CHA prepared from 1- methylpiperidone (2a-e). The histone deacetylase (HDAC) inhibitory activity, lipophilicity and acute toxicity were influenced by the length amino acids (size) (Glycine < Alanine < Valine < Leucine < Phenylalanine). All compounds bearing spiro-N-methylpiperidine ring (2a-e) are non-toxic up to 1250 mg/kg dose, while compounds bearing spiro-tetramethylpiperidine ring (1a-e) exhibit moderate toxicity which increases with increasing lipophility, but not excite at 400 mg/kg., Conclusion: It was shown that the use of combination of non-toxic doses of cisplatin (cPt) or cyclophosphamide with CHA in most cases result in the appearance of a considerable anti-tumor effect of cytostatics. The highest chemosensitizing activity with respect to leukemia Р388 is demonstrated by the CHA derivatives of Valine 1c or 2c., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Iron-chelating activity of synthesized spirocyclic hydroxamic acids, their toxicity, and effects on mitochondrial function were studied using primary culture of cerebral cortical neurons from newborn rats. All tested compounds effectively chelated Fe(II) ions. Activity of spirocyclic hydroxamic acids more strictly depended on the structure their piperidine, but not imidazolidine fragment. All compounds were non-toxic for normal neuronal culture.

In experimental animals with tumors it was studied antitumor activity of spirocyclic hydroxamic acids which could be classified as targeted agents as their target was enzyme histonedeacetylase, which was involved in the neoplastic process. The results showed that the hydroxamic acids were chemosensitizers for anticancer agents increasing their efficacy and enabling the researchers to reduce significantly the therapeutic dose. Also it was showed that hydroxamic acid, containing nitrogen mustard, was effective in the action on tumors with phenotype and genotype of multidrug resistance.

The neuroprotective action of hybrid structures based on fullerene C60 with attached proline amino acid has been studied. Hybrid structures contained natural antioxidant carnosine or addends with one or two nitrate groups. It has been shown that all studied compounds had antioxidant activity and decreased the concentration of malondialdehyde in homogenates of the rat brain. Compound 1, which contained the antioxidant carnosine, has been found to be the most effective antioxidant. All compounds except IV and V inhibited the activity of monoamine oxidase B, while compounds I-IV increased the activity of monoamine oxidase A. All investigated compounds inhibited glutamate-induced Ca2+ uptake into synaptosomes of the rat brain cortex. Compound III, containing two nitrate groups, has been found to be the most effective inhibitor. This compound caused a significant increase of the currents of AMPA receptors (AMPA, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid).

The action of heterocyclic amides series (ethosuximide, phenytoin, primidone) on lipid peroxidation and membrane bound monoamine oxidases A and B under stress condition has been studied. The intraperitoneal injection of the drugs resulted in enhancement of SOD, decrease of brain malondialdehyde content and mitochondrial activity of monoamine oxidases A and B.

The dynamics of total protein biosynthesis and procollagen biosynthesis in skeletal muscle of injury tissues with the antioxidant BHT (dibunol) treatment and with common healing were studied. The obtained date indicate that the AO treatment reduce the rate of biosynthesis both the total proteins and procollagen at the 3th day of healing. Dibunol also considerably reduce the protein biosynthesis in adrenals and brake of corticosteroids biogenesis as measured by ESR-signals intensity of reduced adrenodoxine. AO treatment also reduce the protein biosynthesis in thymus, spleen and bone marrow. The lowering of functional activity of endocrine and immune systems indicate that the AO significantly inhibit the systemic reactions of organism induced by acute wound affect. It was suggested that as "primary mediator" of stress-reaction may be considered lipoperoxide radicals and decay products of lipohydroperoide.