Danylo Kaminskyy

Synthesis and in vitro anticancer activity of 2,4-azolidinedione-acetic acids derivatives.

The synthesis and evaluation of anticancer activity of 2,4-thia(imida)zolidinedione-3- and 5-acetic acids amides were described. The structures of compounds were determined by IR, (1)H NMR, and MS analysis. In vitro anticancer activity of these compounds has been tested in National Cancer Institute (NCI) and the relationships between structure and anticancer activity are discussed. Among 2,4-azolidinedione-acetic acids derivatives 2-[5-(4-chlorobenzylidene)-2,4-dioxo-imidazolidin-3-yl]-N-(2-trifluoromethyl-phenyl)-acetamide (Ic) was superior to other related compounds in terms of high selectivity for the leukemia CCRF-CEM (logGI(50)=-6.06), HL-60(TB) (logGI(50)=-6.53), MOLT-4 (logGI(50)=-6.52) and SR (logGI(50)=-6.51) cell lines.

A Facile Synthesis and Anticancer Activity Evaluation of Spiro(Thiazolidinone-Isatin) Conjugates

The synthesis and evaluation of the anticancer activity of 3′-aryl-5′-arylidene-spiro[3H-indole-3,2′-thiazolidine]-2,4′(1H)-diones and spiro[3H-indole-3,2′-thi-azolidine]-2,4′(1H)-dione-3′-alkanoic acid esters were described. The structure of the compounds was determined by 1H and 13C NMR and their in vitro anticancer activity was tested in the National Cancer Institute. Among the tested compounds, (5′Z)-5′-(benzylidene)-3′-(4-chlorophenyl)spiro[3H-indole-3,2′-thia-zolidine]-2,4′(1H)-dione (IIa) and (5′Z)-3′-(4-chlorophenyl)-5′-[4-(1-methylethyl)-benzylidene]spiro[3H-indole-3,2′-thiazolidine]-2,4′(1H)-dione (IIb) were superior to other related compounds.

Isothiocoumarin-3-carboxylic acid derivatives: Synthesis, anticancer and antitrypanosomal activity evaluation

A series of new isothiocoumarin-3-carboxylic acids derivatives had been obtained based on the 5-arylidenerhodanines hydrolysis. Anticancer activity screening allowed identification of 7,8-dimethoxy-1-oxo-1H-isothiochromene-3-carboxylic acid (4-phenylthiazol-2-yl)-amide (30) with the highest level of antimitotic activity (GI50NCI-H322M/NSC Lung Cancer = 1.28 μM). Evaluation of the antitrypanosomal activity against Trypanosoma brucei brucei showed that investigated compounds did not exhibit significant antiparasitic effects. Additionally, the most pharmacologically attractive compounds were non-toxic and well tolerated by the experimental animals.

The distribution of 4-hydroxynonenal-modified proteins in gastric mucosa of duodenal peptic ulcer patients

This study used monoclonal antibody specific for 4-hydroxynonenal (HNE)-histidine to evaluate immunohistochemical distribution of HNE–protein adducts in gastric mucosa biopsies of 52 peptic ulcer patients (all positive for H. pylori) and of 20 healthy volunteers (eight positive and 12 negative for H. pylori). HNE-modified proteins were present in glandular epithelium in all subjects, both patients with duodenal peptic ulcer and healthy subjects. Hence, the presence of HNE did not appear to be related to the presence of H. pylori. However, in patients with duodenal peptic ulcer accumulation of HNE-protein adducts was frequently observed also in nuclei, while in the control group such subcellular distribution of HNE was not observed at all. This study shows physiological presence of HNE in human gastric mucosa, but also suggests its role in pathology of gastric dysfunction in duodenal peptic ulcer patients manifested by accumulation of HNE-protein adducts in particular in nuclei of gastric glandular epithelium.

Biomarkers of oxidative and nitro‐oxidative stress: conventional and novel approaches

The concept of oxidative stress (OS) that connects altered redox biology with various diseases was introduced 30 years ago and has generated intensive research over the past two decades. Whereas it is now commonly accepted that macromolecule oxidation in response to ROS is associated with a variety of pathologies, the emergence of NO as a key regulator of redox signalling has led to the discovery of the pathophysiological significance of reactive nitrogen species (RNS). RNS can elicit various modifications of macromolecules and lead to nitrative or nitro‐OS. In order to investigate oxidative and nitro‐OS in human and in live animal models, circulating biomarker assays have been developed. This article provides an overview of key biomarkers used to assess lipid peroxidation and NO/NO2 signalling, thereby stressing the necessity to analyse several OS biomarkers in relation to the overall (aerobic) metabolism and health condition of patients. In addition, the potential interest of heart rate variability as the non‐invasive integrative biomarker of OS is discussed.

Antifibrotic and anticancer action of 5-ene amino/iminothiazolidinones.

Here we describe the synthesis and the antifibrotic and anticancer activity determination of amino(imino)thiazolidinone derivatives. An efficient one-pot three-component reaction which involved [2 + 3]-cyclocondensation and Knoevenagel condensation was used for the synthesis of 5-ene-2-amino(imino)-4-thiazolidinones. Following amino-imino tautomerism, the compound structures were confirmed by X-ray analysis. Comparison of SRB assays on fibroblasts and cancer cells revealed that compounds which significantly reduced the viability of fibroblasts did not possess an anticancer effect. A series of thiazolidinone derivatives as interesting candidates for further testing has been identified. Among the tested compounds 2-{3-furan-2-ylmethyl-2-[(2-methyl-3-phenylallylidene)hydrazono]-thiazolidin-4-one-5-yl}-N-(3-trifluoromethylphenyl)-acetamide (5), N-(2-methoxyphenyl)-2-[5-(4-oxothiazolidin-2-ylideneamino)-[1,3,4]thiadiazol-2-ylsulfanyl]-acetamide (12), 3-[3-allyl-4-oxo-2-(thiazol-2-ylimino)thiazolidin-5-ylidene]-1,3-dihydroindol-2-one (33), and 5(Z)-(thiophen-2-ylmethylene)-4-(4-chlorophenylamino)thiazol-2(5H)-one (34) possessed high antifibrotic activity levels, had a similar effect as Pirfenidone, and did not scavenge superoxide radicals. Their antifibrotic potential was confirmed using the xCelligence system.

Activation of aerobic metabolism by Amaranth oil improves heart rate variability both in athletes and patients with type 2 diabetes mellitus

The aim of present research was to study the effects of Amaranth oil (AmO) supplementation on aerobic metabolism and heart rate variability (HRV) in type 2 diabetes mellitus patients and in athletes. Several parameters of aerobic metabolism and HRV were assessed. Supplementation with AmO caused mild pro-oxidant activity resulting in improved uptake of oxidative destruction products and modulation of catalase and SOD activity with subsequent development of an antioxidant effect. These findings were very distinct in athletes but less pronounced in diabetics. Redistribution of haemoglobin ligands in athletes indicates involvement of haemoproteins in free radical reactions during AmO supplementation. Improvement in HRV by daily consumption of AmO as observed in both study groups suggested increased production of endogenous oxygen and enhancement of the cardio-respiratory function. The advantage of activation of aerobic metabolism in OS-related disorders resulting in improved self-organization of the living system and hormetic reaction mechanisms are discussed.

The effect of Amaranth oil on monolayers of artificial lipids and hepatocyte plasma membranes with adrenalin-induced stress

In this paper the oil from seeds of Amaranthus cruentus L. (AmO) was shown to be an efficient modulator of the physical chemical properties of artificial lipid and rat hepatocyte plasma membranes. AmO improved the membrane stability, their stress resistance and the adsorption of neurotensin to plasma membranes with the distinct biphasic interactions being observed even after adrenalin stress exposure. The analysis of pro-/antioxidant balance in rat blood revealed a mild prooxidant activity after AmO intake, which was accompanied by accumulation of oxidative destruction products in plasma membranes. This prooxidant action of AmO was corroborated in vitro in an adrenalin autooxidation model. On the other hand, the observed improved resistance to adrenalin stress in AmO supplemented rats was associated with an antioxidant response in blood and plasma membrane studies. The AmO effects can be attributed to the modulation of the metabolic pathways involved into oxygen and free radical homeostasis.

Study of aerobic metabolism parameters and heart rate variability and their correlations in elite athletes: a modulatory effect of amaranth oil

Abstract Oxidative stress (OS) and decreased heart rate variability (HRV) are known to be associated with overtraining in athletes. Therefore it is extremely important to estimate profoundness of OS and efficiency of its correction with easy-to-use noninvasive methods. The impact of oil derived from the amaranth (Amaranthus cruentus L.) seeds (AmO) on some parameters of aerobic metabolism and HRV was studied in elite athletes. Possible mechanisms explaining the relationship between HRV and aerobic metabolism were estimated with correlation analysis. The effects of AmO administration (1 ml of concentrated oil per day for 21 days) were studied in 36 competitive male athletes. Short time ECG records were performed in supine and orthostatic position before and after AmO administration, time and frequency domain HRV parameters were calculated. The activities of catalase, superoxide dismutase, levels of thiobarbituric acid reactive species, oxidative modification proteins (OMP), medium mass molecules, hemoglobi...

5-Ene-4-thiazolidinones – An efficient tool in medicinal chemistry

Abstract The presented review is an attempt to summarize a huge volume of data on 5-ene-4-thiazolidinones being a widely studied class of small molecules used in modern organic and medicinal chemistry. The manuscript covers approaches to the synthesis of 5-ene-4-thiazolidinone derivatives: modification of the C5 position of the basic core; synthesis of the target compounds in the one-pot or multistage reactions or transformation of other related heterocycles. The most prominent pharmacological profiles of 5-ene derivatives of different 4-thiazolidinone subtypes belonging to hit-, lead-compounds, drug-candidates and drugs as well as the most studied targets have been discussed. Currently target compounds (especially 5-en-rhodanines) are assigned as frequent hitters or pan-assay interference compounds (PAINS) within high-throughput screening campaigns. Nevertheless, the crucial impact of the presence/nature of C5 substituent (namely 5-ene) on the pharmacological effects of 5-ene-4-thiazolidinones was confirmed by the numerous listed findings from the original articles. The main directions for active 5-ene-4-thiazolidinones optimization have been shown: i) complication of the fragment in the C5 position; ii) introduction of the substituents in the N3 position (especially fragments with carboxylic group or its derivatives); iii) annealing in complex heterocyclic systems; iv) combination with other pharmacologically attractive fragments within hybrid pharmacophore approach. Moreover, the utilization of 5-ene-4-thiazolidinones in the synthesis of complex compounds with potent pharmacological application is described. The chemical transformations cover mainly the reactions which involve the exocyclic double bond in C5 position of the main core and correspond to the abovementioned direction of the 5-ene-4-thiazolidinone modification.