RESUMEN
A range of hybrid molecules incorporating the ciminalum moiety in the thiazolidinone ring demonstrate significant anticancer and antimicrobial properties. Therefore, the aim of our study was to evaluate the properties and mechanism of action of two 4-thiazolidinone-based derivatives, i.e., 3-{5-[(Z,2Z)-2-chloro-3-(4-nitrophenyl)-2-propenylidene]-4-oxo-2-thioxothiazolidin-3-yl}propanoic acid (Les-45) and 5-[2-chloro-3-(4-nitrophenyl)-2-propenylidene]-2-(3-hydroxyphenylamino)thiazol-4(5H)-one (Les-247). In our study, we analyzed the impact of Les-45 and Les-247 on metabolic activity, caspase-3 activity, and the expression of genes and proteins related to inflammatory and antioxidant defenses and cytoskeleton rearrangement in healthy human fibroblasts (BJ) and a human lung carcinoma cell line (A549). The cells were exposed to increasing concentrations (1 nM to 100 µM) of the studied compounds for 24 h and 48 h. A decrease in the metabolic activity in the BJ and A549 cell lines was induced by both compounds at a concentration range from 10 to 100 µM. Both compounds decreased the mRNA expression of NRF2 (nuclear factor erythroid 2-related factor 2) and ß-actin in the BJ cells. Interestingly, a significant decrease in the level of NF-κB gene and protein expression was detected in the BJ cell line, suggesting a direct impact of the studied compounds on the inhibition of inflammation. However, more studies are needed due to the ability of Les-45 and Les-247 to interfere with the tubulin/actin cytoskeleton, i.e., a critical system existing in eukaryotic cells.
Asunto(s)
FN-kappa B , Transducción de Señal , Tiazolidinas , Humanos , Tiazolidinas/farmacología , Tiazolidinas/química , FN-kappa B/metabolismo , Transducción de Señal/efectos de los fármacos , Células A549 , Fibroblastos/metabolismo , Fibroblastos/efectos de los fármacos , Antioxidantes/farmacología , Antioxidantes/químicaRESUMEN
Anticonvulsant drug discovery has achieved significant progress; however, pharmacotherapy of epilepsy continues to be a challenge for modern medicine and pharmacy. To expand the chemical space of heterocycles as potential antiepileptic agents, herein we report on the synthesis and evaluation of anticonvulsant properties of a series of thiopyrano[2,3-d]thiazoles. The studied heterocycles are characterized by satisfactory drug-likeness and pharmacokinetics properties, calculated in silico using SwissADME. The anticonvulsant activity of thiopyrano[2,3-d]thiazole derivatives was evaluated in vivo using the subcutaneous pentylenetetrazole test. Three hits, that is, compounds 12, 14, and 16, that caused a pronounced anticonvulsant effect were identified. Derivatives 12, 14, and 16 positively affected the latent period of onset of clonic seizures, number of seizures, mortality rate, and duration of the seizure period of animals under experimental conditions. The anticonvulsant properties of compound 14 were equivalent to the effect of the reference drug, sodium valproate. All hit compounds are characterized by satisfying toxicity properties in the human lymphocytes and HEK293 cell line. The most active hit 14 possesses a potential affinity with the GABAA receptor in the molecular docking study and forms a stable complex in the molecular dynamics experiments equal to diazepam. Preliminary SAR results were obtained and discussed based on screening data.
RESUMEN
Cancer is one of the most important problems of modern societies. Recently, studies have reported the anticancer properties of rosiglitazone related to its ability to bind peroxisome proliferator receptor γ (PPARγ), which has various effects on cancer and can inhibit cell proliferation. In this study, we investigated the effect of new 4-thiazolidinone (4-TZD) hybrids Les-4369 and Les-3467 and their effect on reactive oxygen species (ROS) production, metabolic activity, lactate dehydrogenase (LDH) release, caspase-3 activity, and gene and protein expression in human foreskin fibroblast (BJ) cells and lung adenocarcinoma (A549) cells. The ROS production and caspase-3 activity were mainly increased in the micromolar concentrations of the studied compounds in both cell lines. Les-3467 and Les-4369 increased the mRNA expression of PPARG, P53 (tumor protein P53), and ATM (ATM serine/threonine kinase) in the BJ cells, while the mRNA expression of these genes (except PPARG) was mainly decreased in the A549 cells treated with both of the tested compounds. Our results indicate a decrease in the protein expression of AhR, PPARγ, and PARP-1 in the BJ cells exposed to 1 µM Les-3467 and Les-4369. In the A549 cells, the protein expression of AhR, PPARγ, and PARP-1 increased in the treatment with 1 µM Les-3467 and Les-4369. We have also shown the PPARγ modulatory properties of Les-3467 and Les-4369. However, both compounds prove weak anticancer properties evidenced by their action at high concentrations and non-selective effects against BJ and A549 cells.
Asunto(s)
PPAR gamma , Pirazoles , Especies Reactivas de Oxígeno , Humanos , Células A549 , PPAR gamma/metabolismo , PPAR gamma/genética , Especies Reactivas de Oxígeno/metabolismo , Pirazoles/farmacología , Tiazolidinas/farmacología , Indoles/farmacología , Caspasa 3/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética , Proliferación Celular/efectos de los fármacos , Antineoplásicos/farmacología , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Apoptosis/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismoRESUMEN
A novel 4-thiazolidinone derivative Les-6490 (pyrazol-4-thiazolidinone hybrid) was designed, synthesized, and characterized by spectral data. The compound was screened for its antimicrobial activity against some pathogenic bacteria and fungi and showed activity against Staphylococcus and Saccharomyces cerevisiae (the Minimum Inhibitory Concentration (MIC) 820 µM). The compound was studied in the rat adjuvant arthritis model (Freund's Adjuvant) in vivo. Parietal and fecal microbial composition using 16S rRNA metagenome sequences was checked. We employed a range of analytical techniques, including Taxonomic Profiling (Taxa Analysis), Diversity Metrics (Alpha and Beta Diversity Analysis), Multivariate Statistical Methods (Principal Coordinates Analysis, Principal Component Analysis, Non-Metric Multidimensional Scaling), Clustering Analysis (Unweighted Pair-group Method with Arithmetic Mean), and Comparative Statistical Approaches (Community Differences Analysis, Between Group Variation Analysis, Metastat Analysis). The compound significantly impacted an increasing level of anti-inflammatory microorganisms (Blautia, Faecalibacterium prausnitzii, Succivibrionaceae, and Coriobacteriales) relative recovery of fecal microbiota composition. Anti-Treponemal activity in vivo was also noted. The tested compound Les-6490 has potential prebiotic activity with an indirect anti-inflammatory effect.
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Design of tubulin inhibitors as anticancer drugs dynamically developed over the past 20 years. The modern arsenal of potential tubulin-targeting anticancer agents is represented by small molecules, monoclonal antibodies, and antibody-drug conjugates. Moreover, targeting tubulin has been a successful strategy in the development of antiparasitic drugs. In the present review, an overall picture of the research and development of potential tubulin-targeting agents using small molecules between 2018 and 2023 is provided. The data about some most often used and prospective chemotypes of small molecules (privileged heterocycles, moieties of natural molecules) and synthetic methodologies (analogue-based, fragment-based drug design, molecular hybridization) applied for the design of novel agents with an impact on the tubulin system are summarized. The design and prospects of multi-target agents with an impact on the tubulin system were also highlighted. Reported in the review data contribute to the "structure-activity" profile of tubulin-targeting small molecules as anticancer and antiparasitic agents and will be useful for the application by medicinal chemists in further exploration, design, improvement, and optimization of this class of molecules.
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Antineoplásicos , Moduladores de Tubulina , Moduladores de Tubulina/farmacología , Tubulina (Proteína)/metabolismo , Antiparasitarios/farmacología , Estudios Prospectivos , Antineoplásicos/farmacología , Relación Estructura-ActividadRESUMEN
Aromatase is an enzyme that plays a crucial role in the biosynthesis of estrogens, which are hormones that contribute to the growth of certain types of breast cancer. In particular, aromatase catalyzes the conversion of androgens (male hormones) into estrogens (female hormones) in various tissues, including the adrenal glands, ovaries, and adipose tissue. Given the role of estrogen in promoting the growth of hormone-receptor-positive breast cancers, aromatase has become an important molecular target for the development of anticancer agents. Aromatase inhibitors can be classified into two main groups based on their chemical structure: steroidal and non-steroidal inhibitors. This work presents a review of the literature from the last ten years regarding the search for new aromatase inhibitors. We present the directions of search, taking into account the impact of structure modifications on anticancer activity.
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Inhibidores de la Aromatasa , Aromatasa , Femenino , Masculino , Humanos , Inhibidores de la Aromatasa/farmacología , Inhibidores de la Aromatasa/uso terapéutico , Estrógenos , Tejido Adiposo , AndrógenosRESUMEN
Antibody-Drug Conjugates (ADC) are a new class of anticancer therapeutics with immense potential. They have been rapidly advancing in the last two decades. This fast speed of development has become possible due to several new technologies and methods. One of them is Click Chemistry, an approach that was created only two decades ago, but already is actively utilized for bioconjugation, material science and drug discovery. In this review, we researched the impact of Click Chemistry reactions on the synthesis and development of ADCs. The information about the most frequently utilized reactions, such as Michael's addition, Copper-catalyzed azide-alkyne [3+2] cycloaddition (CuAAC), Strain-promoted azide-alkyne [3+2] cycloaddition (SPAAC), oxime bond formation, hydrazine-iso-Pictet-Spengler Ligation (HIPS), Diels-Alder reactions have been summarized. The implementation of thiol-maleimide Click Chemistry reaction in the synthesis of numerous FDA-approved Antibody-Drug Conjugates has been reported. The data amassed in the present review provides better understanding of the importance of Click Chemistry in the synthesis, development and improvement of the Antibody-Drug Conjugates and it will be helpful for further researches related to ADCs.
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Azidas , Química Clic , Maleimidas , Compuestos de Sulfhidrilo , Azidas/química , Alquinos/química , Reacción de Cicloadición , Cobre/químicaRESUMEN
Endocytosis is one of the major ways cells communicate with their environment. This process is frequently hijacked by pathogens. Endocytosis also participates in the oncogenic transformation. Here, we review the approaches to inhibit endocytosis, discuss chemical inhibitors of this process, and discuss potential clinical applications of the endocytosis inhibitors.
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Endocitosis , Endocitosis/efectos de los fármacosRESUMEN
The hybrid heterocyclic molecules are perspective materials in the development of anticancer drugs. Here, the pyrrolidinedione-thiazolidinone hybrid molecules were designed as potent anticancer agents. This study aimed to investigate the cytotoxic effect of three derivatives 1-(4-hydroxyphenyl)-, 1-(4-chlorophenyl)- and 1-(4-bromophenyl)-3-[5-[2-chloro-3-(4-nitrophenyl)prop-2-enylidene]-4-oxo-2-thioxothiazolidine-3-yl]pyrrolidine-2,5-diones (Les-6287, Les-6294, and Les-6328, respectively), their effect on the production of the reactive oxygen species (ROS), apoptosis induction, and expression of genes - PPARγ, AHR, and NRFL2 - whose products are important in metabolism in human tongue squamous cell carcinoma cells of SCC-15 line. The results of resazurin reduction and lactate dehydrogenase (LDH) release assays proved the toxicity of the tested derivatives for the SCC-15 cells. Les-6287, Les-6294, and Les-6328 inhibited the viability of SCC-15 cells with the half-maximal effective concentration (EC50) in the range of 10.18-32.75 µM at 24 and 48 h treatment. These derivatives reduced the metabolism of SCC-15 cells with the half-maximal inhibitory concentration (IC50) of 6.72-39.85 µM at 24 and 48 h treatment. Les-6287, Les-6294, and Les-6328 reduced the metabolism of normal human keratinocytes of HaCaT line murine fibroblasts of Balb/c 3T3 line to a lesser extent. The compounds used in a range from 50 to 100 µM concentrations decreased ROS production in the SCC-15 cells. The derivatives Les-6287 and Les-6328 decreased the level of expression of mRNA of PPARγ, AHR, and NRFL2 genes in these cells at PPARγ siRNA knockdown and without it. Thus, the anticancer effect of studied hybrid pyrrolidinedione-thiazolidinones in the SCC-15 carcinoma cells is accompanied by a reduction of their metabolic activity and ROS level, and increase in caspase 3 activity. However, these changes are not the result of direct interaction of Les-6287, Les-6294, and Les-6328 with the PPARγ molecule.
Asunto(s)
Antineoplásicos , Carcinoma de Células Escamosas , Neoplasias de la Lengua , Humanos , Animales , Ratones , Línea Celular Tumoral , Carcinoma de Células Escamosas/tratamiento farmacológico , Especies Reactivas de Oxígeno/metabolismo , PPAR gamma/farmacología , Apoptosis , Neoplasias de la Lengua/tratamiento farmacológico , Antineoplásicos/farmacología , Antineoplásicos/uso terapéuticoRESUMEN
Combining chemotherapy with immunotherapy still remains a regimen in anticancer therapy. Novel 4-thiazolidinone-bearing hybrid molecules possess well-documented anticancer activity, and together with anti-HER2 antibodies, may represent a promising strategy in treating patients with gastric cancer with confirmed human epidermal growth factor receptor 2 (HER2) expression. The aim of the study was to synthesize a new 4-thiazolidinone derivative (Les-4367) and investigate its molecular mechanism of action in combination with trastuzumab or pertuzumab in human AGS gastric cancer cells. AGS cell viability and antiproliferative potential were examined. The effect of the tested combinations as well as monotherapy on apoptosis and autophagy was also determined. Metalloproteinase-2 (MMP-2), intercellular adhesion molecule 1 (ICAM-1), pro-inflammatory and anti-inflammatory cytokine concentrations were also demonstrated by the ELISA technique. We proved that pertuzumab and trastuzumab were very effective in increasing the sensitivity of AGS gastric cancer cells to novel Les-4367. The molecular mechanism of action of the tested combination is connected with the induction of apoptosis. Additionally, the anticancer activity is not associated with the autophagy process. Decreased concentrations of pro-inflammatory cytokines, MMP-2 and ICAM-1-were observed. The novel combination of drugs based on anti-HER2 antibodies with Les-4367 is a promising strategy against AGS gastric cancer cells.
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Neoplasias Gástricas , Tiazolidinas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Línea Celular Tumoral , Molécula 1 de Adhesión Intercelular , Metaloproteinasa 2 de la Matriz , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/metabolismo , Trastuzumab/farmacología , Tiazolidinas/farmacologíaRESUMEN
Oncological diseases have currently reached an epidemic scale, especially in industrialized countries. Such a situation has prompted complex studies in medicinal chemistry focused on the research and development of novel effective anticancer drugs. In this review, the data concerning new 4-thiazolidinone-bearing hybrid molecules with potential anticancer activity reported during the period from the years 2017-2022 are summarized. The main emphasis is on the application of molecular hybridization methodologies and strategies in the design of small molecules as anticancer agents. Based on the analyzed data, it was observed that the main directions in this field are the hybridization of scaffolds, the hybrid-pharmacophore approach, and the analogue-based drug design of 4-thiazolidinone cores with early approved drugs, natural compounds, and privileged heterocyclic scaffolds. The mentioned design approaches are effective tools/sources for the generation of hit/lead compounds with anticancer activity and will be relevant to future studies.
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Antineoplásicos , Diseño de Fármacos , Tiazolidinas/farmacología , Tiazolidinas/química , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Antineoplásicos/química , Química FarmacéuticaRESUMEN
Novel pyridine-thiazole hybrid molecules were synthesized and subjected to physico-chemical characterization and screening of their cytotoxic action towards a panel of cell lines derived from different types of tumors (carcinomas of colon, breast, and lung, glioblastoma and leukemia), and normal human keratinocytes, for comparison. High antiproliferative activity of the 3-(2-fluorophenyl)-1-[4-methyl-2-(pyridin-2-ylamino)-thiazol-5-yl]-propenone 3 and 4-(2-{1-(2-fluorophenyl)-3-[4-methyl-2-(pyridin-2-ylamino)-thiazol-5-yl]-3-oxopropylsulfanyl}-acetylamino)-benzoic acid ethyl ester 4 was revealed. The IC50 of the compound 3 in HL-60 cells of the acute human promyelocytic leukemia was 0.57 µM, while in the pseudo-normal human cell lines, the IC50 of this compound was >50 µM, which suggests that the compounds 3 and 4 might be perspective anticancer agents. The detected selectivity of the derivatives 3 and 4 for cancer cell lines inspired us to study the mechanisms of their cytotoxic action. It was shown that preincubation of tumor cells with Fluzaparib (inhibitor of PARP1) reduced the cytotoxic activity of the derivatives 3 and 4 by more than twice. The ability of these compounds to affect DNA nativity and cause changes in nucleus morphology allows for the suggestion that the mechanism of action of the novel pyridine-thiazole derivatives might be related to inducing the genetic instability in tumor cells.
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Antineoplásicos , Leucemia , Neoplasias , Antineoplásicos/química , Antineoplásicos/farmacología , Ácido Benzoico/farmacología , Línea Celular Tumoral , Proliferación Celular , ADN/farmacología , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Ésteres/farmacología , Humanos , Estructura Molecular , Piridinas/farmacología , Relación Estructura-Actividad , Tiazoles/química , Tiazoles/farmacologíaRESUMEN
Development of cancer drug-resistance is still an ongoing problem in the modern anticancer treatment. Therefore, there is a need to search for a new active substance, which may become a potential anticancer agent. 4-Thiazolidinones are well-described substances with cytotoxicity against cancer cells in vitro. Therefore, the aim of this study was to evaluate the effect of two 4-thiazolidinone-based derivatives (Les-2769 and Les-3266) on the PPARγ-dependent cytotoxicity in normal human skin fibroblasts (BJ) and squamous cell carcinoma (SCC-15) in vitro. The data obtained showed a cytotoxic effect of Les-2769 and Les-3266 used in micromolar concentrations on SCC-15 and BJ cells, manifesting by a decrease in the metabolic activity, an increase in the release of lactate dehydrogenase, and caspase-3 activity. The co-treatment of the cells with Les-3266 and an antagonist (GW9662) or an agonist (rosiglitazone) of the PPARγ receptor induced changes in the above-mentioned parameters in the BJ and SCC-15 cells, compared to the Les-3266 alone exposure; this was not found in the Les-2769-treated cells. The further analysis of the compounds indicated changes in the expression of the PPARγ, KI67, and NF-κB genes. Moreover, the tested compounds caused an increase in the level of PPARγ mRNA expression in a similar way to rosiglitazone in SCC-15, which may indicate the affinity of the compounds for PPARγ. Molecular docking is consistent with experimental in vitro data about the potential agonistic activity of Les-2769 and Les-3266 towards PPARγ receptors. Summarizing, the anticancer effect of both compounds was observed in the SCC-15 cells in vitro; moreover, the mechanism of action of Les-3266 in cells is mediated probably by interaction with the PPARγ receptor pathway, which needs in-depth study.
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Antineoplásicos , Tiazolidinedionas , Antineoplásicos/farmacología , Humanos , Simulación del Acoplamiento Molecular , PPAR gamma/metabolismo , Rosiglitazona , Tiazolidinedionas/farmacología , Tiazolidinas/farmacologíaRESUMEN
A series of novel pyrrolidinedione-thiazolidinones was synthesized and subjected to physico-chemical characteristics. They were screened on a panel of cell lines representing different types of cancer, as well as normal human keratynocytes and lymphocytes of peripheral human blood. High antiproliferative activity of 1-(4-chlorophenyl)- and 1-(4-hydroxyphenyl)-3-{5-[(Z,2Z)-2-chloro-3-(4-nitrophenyl)-2-propenylidene]-4-oxo-2-thioxothiazolidin-3-yl}-1-(4-hydroxyphenyl)-pyrrolidine-2,5-diones 2a and 2b was revealed along with satisfactory cytotoxicity characteristics. Human T-leukemia cells of Jurkat line were the most sensitive to the action of 2a, 2b and 5-(2-allyloxybenzylidene) derivative 2f. At the same time, synthesized compounds demonstrated low toxicity towards normal human keratinocytes of HaCaT line and mitogen-activated lymphocytes of peripheral blood of healthy human donor. The compounds 2а and 2b demonstrated high selectivity (SI >9.2) towards studied leukemia, lung, breast, cervical, colon carcinoma and glioblastoma cells. Compounds 2a, 2b induced mitochondria-dependent apoptosis in treated Jurkat T-cells via increasing the level of proapoptotic Bax and EndoG proteins, and decreasing the level of antiapoptotic Bcl-2 protein. The cytotoxic action of compounds 2a, 2b towards Jurkat T-cells was associated with the single-strand brakes in DNA and its inter-nucleosomal fragmentation, without significant intercalation of these compounds into the DNA molecule. Compounds 2a, 2b did not induce significant DNA damage and changes in morphology of mitogen-activated lymphocytes of peripheral blood of healthy donor. Altogether, these data demonstrated anticancer potential of novel hybrid pyrrolidinedione-thiazolidinones which were relatively non-toxic for normal human cells.
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Antineoplásicos , Leucemia , Antineoplásicos/química , Apoptosis , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Mitógenos/farmacología , Succinimidas/farmacologíaRESUMEN
The present paper is devoted to the search for drug-like molecules with anticancer properties using the thiazolo[3,2-b][1,2,4]triazole-6-one scaffold. A series of 24 novel thiazolo-[3,2-b][1,2,4]triazole-6-ones with 5-aryl(heteryl)idene- and 5-aminomethylidene-moieties has been synthesized employing three-component and three-stage synthetic protocols. A mixture of Z/E-isomers was obtained in solution for the synthesized 5-aminomethylidene-thiazolo[3,2-b]-[1,2,4]triazole-6-ones. The compounds have been studied for their antitumor activity in the NCI 60 lines screen. Some compounds present excellent anticancer properties at 10 µM. Derivatives 2h and 2i were the most active against cancer cell lines without causing toxicity to normal somatic (HEK293) cells. A preliminary SAR study had been performed for the synthesized compounds.
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Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Línea Celular , Proliferación Celular/efectos de los fármacos , Cristalografía por Rayos X , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Modelos Moleculares , Estructura Molecular , Relación Estructura-ActividadRESUMEN
A human organism depends on stable glucose blood levels in order to maintain its metabolic needs. Glucose is considered to be the most important energy source, and glycolysis is postulated as a backbone pathway. However, when the glucose supply is limited, ketone bodies and amino acids can be used to produce enough ATP. In contrast, for the functioning of the pentose phosphate pathway (PPP) glucose is essential and cannot be substituted by other metabolites. The PPP generates and maintains the levels of nicotinamide adenine dinucleotide phosphate (NADPH) needed for the reduction in oxidized glutathione and protein thiols, the synthesis of lipids and DNA as well as for xenobiotic detoxification, regulatory redox signaling and counteracting infections. The flux of glucose into a PPP-particularly under extreme oxidative and toxic challenges-is critical for survival, whereas the glycolytic pathway is primarily activated when glucose is abundant, and there is lack of NADP+ that is required for the activation of glucose-6 phosphate dehydrogenase. An important role of glycogen stores in resistance to oxidative challenges is discussed. Current evidences explain the disruptive metabolic effects and detrimental health consequences of chronic nutritional carbohydrate overload, and provide new insights into the positive metabolic effects of intermittent fasting, caloric restriction, exercise, and ketogenic diet through modulation of redox homeostasis.
RESUMEN
A series of novel 2-(5-aminomethylene-4-oxo-2-thioxothiazolidin-3-yl)-3-phenylpropionic acid ethyl esters has been synthesized. Target compounds were evaluated for their trypanocidal activity towards Trypanosoma brucei brucei and Trypanosoma brucei gambiense. Several hit-compounds (8, 10, 12) inhibited growth of the parasites at sub-micromolar concentrations (IC50 0.027-1.936⯵M) and showed significant selectivity indices (SIâ¯=â¯108-1396.2) being non-toxic towards the human primary fibroblasts. The screening of anticancer activity in vitro within NCI DTP protocol allowed to identify active 2-(5-{[5-(2,4-dichlorobenzyl)-thiazol-2-ylamino]-methylene}-4-oxo-2-thioxothiazolidin-3-yl)-3-phenylpropionic acid ethyl ester 14 that demonstrated inhibition against all 59 human tumor cell lines with the average GI50 value of 2.57⯵M. It was established that the activity type (antitrypanosomal or anticancer) as well as its level depends on the character of enamine fragment in the C5 position of thiazolidinone core.