Design and synthesis of uracil/thiouracil based quinoline scaffolds as topoisomerases I/II inhibitors for chemotherapy: A new hybrid navigator with DFT calculation.

In this work, a novel promising hybrid mode of uracil/thiouracil based quinoline pharmacophore i.e. 5a-f was rationalized and synthesized based on rigidification and lipophilic principles, and following the reported pharmacophoric features of camptothecin & doxorubicin. Concurrently, a non-rigid mode pharmacophore i.e. 7a-f was also designed and synthesized. The anti-proliferative activity of the compounds was assessed against three different cancer cell lines, namely A549 lung cancer, MCF-7 breast adenocarcinoma, and HepG-2 hepatic carcinoma. Further, promising candidates were evaluated against A549, and MCF-7 and for their ability to inhibit topoisomerases I &II. Compound 5f was observed to be the most active congener, displaying the highest cell inhibition of 84.4% for topoisomerase I and 92%, for topoisomerase II at a concentration of 100 µM. When its cytotoxicity was evaluated against A549 cells, 5f arrested the cell cycle at the S phase and increased the apoptosis ratio by 46.31%. DFT calculation of 5f showed higher dipole moment and greater negative energy values (-247531.510 kcal/mol) with positive & negative poles, and better stability reflection. Furthermore, molecular docking of 5f to both enzymes showed good agreement with the biological assessment. This study has given insight for further consideration of the highly promising hybrid 5f.

A Computational QSAR, Molecular Docking and In Vitro Cytotoxicity Study of Novel Thiouracil-Based Drugs with Anticancer Activity against Human-DNA Topoisomerase II.

Computational chemistry, molecular docking, and drug design approaches, combined with the biochemical evaluation of the antitumor activity of selected derivatives of the thiouracil-based dihydroindeno pyrido pyrimidines against topoisomerase I and II. The IC50 of other cell lines including the normal human lung cell line W138, lung cancer cell line, A549, breast cancer cell line, MCF-7, cervical cancer, HeLa, and liver cancer cell line HepG2 was evaluated using biochemical methods. The global reactivity descriptors and physicochemical parameters were computed, showing good agreement with the Lipinski and Veber's rules of the drug criteria. The molecular docking study of the ligands with the topoisomerase protein provides the binding sites, binding energies, and deactivation constant for the inhibition pocket. Various biochemical methods were used to evaluate the IC50 of the cell lines. The QSAR model was developed for colorectal cell line HCT as a case study. Four QSAR statistical models were predicted between the IC50 of the colorectal cell line HCT to correlate the anticancer activity and the computed physicochemical and quantum chemical global reactivity descriptors. The predictive power of the models indicates a good correlation between the observed and the predicted activity.

Novel cyanothiouracil and cyanothiocytosine derivatives as concentration-dependent selective inhibitors of U87MG glioblastomas: Adenosine receptor binding and potent PDE4 inhibition.

Thiouracil and thiocytosine are important heterocyclic pharmacophores having pharmacological diversity. Antitumor and antiviral activity is commonly associated with thiouracil and thiocytosine derivatives, which are well known fragments for adenosine receptor affinity with many associated pharmacological properties. In this respect, 33 novel compounds have been synthesized in two groups: 24 thiouracil derivatives (4a-x) and 9 thiocytosine derivatives (5a-i). Antitumor activity of all the compounds was determined in the U87 MG glioblastoma cell line. Compound 5e showed an anti-proliferative IC50 of 1.56 µM, which is slightly higher activity than cisplatin (1.67 µM). The 11 most active compounds showed no signficant binding to adenosine A1, A2A or A2B receptors at 1 µM. Brain tumors express high amounts of phosphodiesterases. Compounds were tested for PDE4 inhibition, and 5e and 5f showed the best potency (5e: 3.42 µM; 5f: 0.97 µM). Remakably, those compounds were also the most active against U87MG. However, the compounds lacked a cytotoxic effect on the HEK293 healthy cell line, which encourages further investigation.

Ruthenium(II) complexes with 6-methyl-2-thiouracil selectively reduce cell proliferation, cause DNA double-strand break and trigger caspase-mediated apoptosis through JNK/p38 pathways in human acute promyelocytic leukemia cells.

Ruthenium(II) complexes with 6-methyl-2-thiouracil cis-[Ru(6m2tu)2(PPh3)2] (1) and [Ru(6m2tu)2(dppb)] (2) (where PPh3 = triphenylphosphine; dppb = 1,4-bis(diphenylphosphino)butane; and 6m2tu = 6-methyl-2-thiouracil) are potent cytotoxic agents and able to bind DNA. The aim of this study was to evaluate in vitro cellular underlying mechanism and in vivo effectiveness of these ruthenium(II) complexes in human acute promyelocytic leukemia HL-60 cells. Both complexes displayed potent and selective cytotoxicity in myeloid leukemia cell lines, and were detected into HL-60 cells. Reduction of the cell proliferation and augmented phosphatidylserine externalization, caspase-3, -8 and -9 activation and loss of mitochondrial transmembrane potential were observed in HL-60 cells treated with both complexes. Cotreatment with Z-VAD(OMe)-FMK, a pan-caspase inhibitor, reduced Ru(II) complexes-induced apoptosis. In addition, both metal complexes induced phosphorylation of histone H2AX (S139), JNK2 (T183/Y185) and p38α (T180/Y182), and cotreatment with JNK/SAPK and p38 MAPK inhibitors reduced complexes-induced apoptosis, indicating DNA double-strand break and activation of caspase-mediated apoptosis through JNK/p38 pathways. Complex 1 also reduced HL-60 cell growth in xenograft model. Overall, the outcome indicated the ruthenium(II) complexes with 6-methyl-2-thiouracil as a novel promising antileukemic drug candidates.

Biomolecules of 2-Thiouracil, 4-Thiouracil and 2,4-Dithiouracil: A DFT Study of the Hydration, Molecular Docking and Effect in DNA:RNAMicrohelixes.

The molecular structure of 2-thiouracil, 4-thiouracil and 2,4-dithiouracil was analyzed under the effect of the first and second hydration shell by using the B3LYP density functional (DFT) method, and the results were compared to those obtained for the uracil molecule. A slight difference in the water distribution appears in these molecules. On the hydration of these molecules several trends in bond lengths and atomic charges were established. The ring in uracil molecule appears easier to be deformed and adapted to different environments as compared to that when it is thio-substituted. Molecular docking calculations of 2-thiouracil against three different pathogens: Bacillus subtilis, Escherichia coli and Candida albicans were carried out. Docking calculations of 2,4-dithiouracil ligand with various targeted proteins were also performed. Different DNA: RNA hybrid microhelixes with uridine, 2-thiouridine, 4-thiouridine and 2,4-dithiouridine nucleosides were optimized in a simple model with three nucleotide base pairs. Two main types of microhelixes were analyzed in detail depending on the intramolecular H-bond of the 2'-OH group. The weaker Watson-Crick (WC) base pair formed with thio-substituted uracil than with unsubstituted ones slightly deforms the helical and backbone parameters, especially with 2,4-dithiouridine. However, the thio-substitution significantly increases the dipole moment of the A-type microhelixes, as well as the rise and propeller twist parameters.

Ru(II) complexes containing uracil nucleobase analogs with cytotoxicity against tumor cells.

We report on chemistry and cytotoxic studies of four new ruthenium (II) complexes containing uracil derivatives. All compounds are neutral, presenting the formula [Ru(PPh3)2(2TU)2] (1), [Ru(PPh3)2(6m2TU)2] (2), [Ru(dppb)(2TU)2] (3) and [Ru(dppb)(6m2TU)2] (4), where PPh3 = triphenylphosphine; dppb = 1,4-bis(diphenylphosphino)butane, 2TU = 2-thiouracil and 6m2TU = 6-methyl-2-thiouracil. They were characterized using NMR, UV-vis and IR spectroscopies, microanalytical analysis and mass spectrometry. Furthermore, the crystal structures of 1-4 were determined by single-crystal X-ray diffraction. The coordination of 2-thiouracil derivatives with ruthenium increases regions able to carry out hydrogen bonds with the biological targets, such as DNA. We evaluated the interaction of the complexes with DNA by UV/Vis spectrophotometric titration, and as a result, the values of DNA-binding constants are in the range of 0.8-1.8 × 104 M-1. Moreover, the interaction of the complexes with BSA was investigated. In vitro, activities against B16-F10 (mouse melanoma), HepG2 (human hepatocellular carcinoma), HL-60 (human promyelocytic leukemia) and K562 (human chronic myelocytic leukemia) and non-tumor cells: PBMC (human peripheral blood mononuclear cells activated with concanavalin A - human lymphoblast) were carried out. Cytotoxicity assays revealed that complexes (2) and (4) present biological activity against tumor cells comparable with oxaliplatin, the reference platinum drug, revealing that they are promising molecules for developing new antitumor compounds.

Thiouracil: Comprehensive profile.

Thiouracil, 2-sulfanylidene-1H-pyrimidin-4-one, has been used as anti-thyroid, coronary vasodilator, and in congestive heart failure. It was found to cause agranulocytosis and it is suspected to be teratogenic and carcinogenic. Owing to its high frequency of adverse reactions, especially agranulocytosis, its use was abandoned in favor of other, less toxic drugs, such as propylthiouracil and methimazole. Thiouracil refers both to a specific molecule consisting of a sulfated uracil and a family of molecules based upon the structure. An important member of this family is propylthiouracil, which is a thiourea antithyroid drug that acts by blocking the production of thyroid hormones; it also inhibits the peripheral deiodination of thyroxine to tri-iodothyronine. This profile is prepared to discuss and explain physical and chemical properties, proprietary and nonproprietary names of thiouracil and propylthiouracil. It also includes uses and applications, methods of preparation, thermal and spectral behavior and methods of analysis. In addition, metabolism, excretion and pharmacology of propylthiouracil are also discussed.

Design, Synthesis, Molecular Modeling, and Biological Evaluation of Novel Thiouracil Derivatives as Potential Antithyroid Agents.

Hyperthyroidism is the result of uncontrolled overproduction of the thyroid hormones. One of the mostly used antithyroid agents is 6-n-propyl-2-thiouracil (PTU). The previously solved X-ray crystal structure of the PTU bound to mammalian lactoperoxidase (LPO) reveals that the LPO-PTU binding site is basically a hydrophobic channel. There are two hydrophobic side chains directed towards the oxygen atom in the C-4 position of the thiouracil ring. In the current study, the structural activity relationship (SAR) was performed on the thiouracil nucleus of PTU to target these hydrophobic side chains and gain more favorable interactions and, in return, more antithyroid activity. Most of the designed compounds show superiority over PTU in reducing the mean serum T4 levels of hyperthyroid rats by 3% to 60%. In addition, the effect of these compounds on the levels of serum T3 was found to be comparable to the effect of PTU treatment. The designed compounds in this study showed a promising activity profile in reducing levels of thyroid hormones and follow up experiments will be needed to confirm the use of the designed compounds as new potential antithyroid agents.

SLAM-ITseq: sequencing cell type-specific transcriptomes without cell sorting.

Cell type-specific transcriptome analysis is an essential tool for understanding biological processes in which diverse types of cells are involved. Although cell isolation methods such as fluorescence-activated cell sorting (FACS) in combination with transcriptome analysis have widely been used so far, their time-consuming and harsh procedures limit their applications. Here, we report a novel in vivo metabolic RNA sequencing method, SLAM-ITseq, which metabolically labels RNA with 4-thiouracil in a specific cell type in vivo followed by detection through an RNA-seq-based method that specifically distinguishes the thiolated uridine by base conversion. This method has successfully identified the cell type-specific transcriptome in three different tissues: endothelial cells in brain, epithelial cells in intestine and adipocytes in white adipose tissue. As this method does not require isolation of cells or RNA prior to the transcriptomic analysis, SLAM-ITseq provides an easy yet accurate snapshot of the transcriptional state in vivo.

Discovery of urinary biomarkers to discriminate between exogenous and semi-endogenous thiouracil in cattle: A parallel-like randomized design.

In the European Union, the use of thyreostats for animal fattening purposes has been banned and monitoring plans have been established to detect potential abuse. However, this is not always straightforward as thyreostats such as thiouracil may also have a semi-endogenous origin. Therefore, this study aimed at defining urinary metabolites, which may aid in defining the origin of detected thiouracil. Hereto, a parallel-like randomized in vivo study was conducted in which calves (n = 8) and cows (n = 8) were subjected to either a control treatment, rapeseed-enriched diet to induce semi-endogenous formation, or thiouracil treatment. Urine samples (n = 330) were assessed through metabolic fingerprinting, employing liquid-chromatography and Q-ExactiveTM Orbitrap mass spectrometry. Urinary fingerprints comprised up to 40,000 features whereby multivariate discriminant analysis was able to point out significant metabolome differences between treatments (Q2(Y) ≥ 0.873). Using the validated models, a total of twelve metabolites (including thiouracil) were assigned marker potential. Combining these markers into age-dependent biomarker panels rendered a tool by which sample classification could be improved in comparison with thiouracil-based thresholds, and this during on-going thiouracil treatment (specificities ≥ 95.2% and sensitivities ≥ 85.7%), post-treatment (sensitivities ≥ 80% for ≥ 24 h after last administration), and simulated low-dose thiouracil treatment (exogenous thiouracil below 30 ng µL-1). Moreover, the metabolic relevance of revealed markers was supported by the suggested identities, for which a structural link with thiouracil could be determined in most cases. The proposed biomarker panels may contribute to a more justified decision-making in monitoring thiouracil abuse.

Synthesis, characterization and molecular docking studies of thiouracil derivatives as potent thymidylate synthase inhibitors and potential anticancer agents.

Thymidylate synthase (TS), one of folate-dependent enzymes, is a key and well-recognized target for anticancer agents. In this study, a series of 6-aryl-5-cyano thiouracil derivatives were designed and synthesized in accordance with essential pharmacophoric features of known TS inhibitors. Nineteen compounds were screened in vitro for their anti-proliferative activities toward HePG-2, MCF-7, HCT-116, and PC-3 cell lines. Compounds [Formula: see text], [Formula: see text], and 24 exhibited high anti-proliferative activity, comparable to that of 5-fluorouracil. Additionally, ten compounds with potent anti-proliferative activities were further evaluated for their ability to inhibit TS enzyme. Six compounds ([Formula: see text], [Formula: see text], [Formula: see text], 22, 23 and 24) demonstrated potent dose-related TS inhibition with [Formula: see text] values ranging from 1.57 to [Formula: see text]. The in vitro TS activity results were consistent with those of the cytotoxicity assay where the most potent anti-proliferative compounds of the series showed good TS inhibitory activity comparable to that of 5-fluorouracil. Furthermore, molecular docking studies were carried out to investigate the binding pattern of the designed compounds with the prospective target, TS (PDB-code: 1JU6).

Hybrids of thienopyrimidinones and thiouracils as anti-tubercular agents: SAR and docking studies.

A number of hybrid molecules containing thienopyrimidinones and thiouracil moieties were designed, synthesized and tested against Mycobacterium tuberculosis H37Ra wherein it was observed that the compounds 11-14 exhibited antitubercular activity in vitro (MIC 7.6-19.1 µg/mL, 12-35 µM) against dormant stage while the compound 15 exhibited antitubercular activity in vitro against dormant (MIC 23.4 µg/mL, 41 µM) as well as active (MIC 25.4 µg/mL, 45 µM) stage. Structural modifications of the compound 15 were carried out to study the structure-activity relationship and it was observed that the compound 18 exhibited antitubercular activity comparable to the compound 15. Cytotoxicity studies revealed that these molecules were non-toxic. The docking study of the compound 15 showed that there was binding with the active site of mycobacterial pantothenate synthetase. Further docking studies led to the synthesis of the compounds 16 and 17 and the antitubercular activity screening results showed that these compounds have significant antitubercular activity. The compounds 15-18 (MIC 11-29 µg/mL, 19-51 µM) can be used as starting points for further optimization. The synthetic strategies used in the present work have potential to prepare a large number of compounds for further refinement of structures and the present results will be very useful in the development of a new class of antimycobacterial agents.

Design, synthesis and antibacterial activities of thiouracil derivatives containing acyl thiourea as SecA inhibitors.

A series of novel thiouracil derivatives containing an acyl thiourea moiety (7a-7x) have been synthesized by structural modification of a lead SecA inhibitor, 2. All the compounds have been evaluated for their antibacterial activities against Bacillus amyloliquefaciens, Staphylococcus aureus, and Bacillus subtilis. Compounds 7c, 7m, 7u, 7v exhibited promising activities against above bacteria. Such four compounds were further tested for their inhibitory activity against SecA ATPase, and the results showed that compounds 7c and 7u had higher inhibitory activities than that of compound 2. Molecular docking work suggests that compound 7u might bind at a pocket close to the ATPase ATP-binding domain.

Design, synthesis and antimicrobial activities of thiouracil derivatives containing triazolo-thiadiazole as SecA inhibitors.

A series of novel thiouracil derivatives containing a triazolo-thiadiazole moiety (7a-7l) have been synthesized by structural modifications on a lead SecA inhibitor, 2. All the compounds have been evaluated for their antibacterial activities against Bacillus amyloliquefaciens, Staphylococcus aureus, and Bacillus subtilis. Compounds 7d and 7g were also tested for their inhibitory activities against SecA ATPase due to their promising antimicrobial activities. The inhibitory activity of compound 7d was found to be higher than that of 2. Molecular docking work suggests that compound 7d might bind at a pocket close to the ATPase ATP-binding domain.

Nanoformulation and antimicrobial evaluation of newly synthesized thiouracil derivatives.

The present work reports the synthesis of a new series of pyridopyrimidine derivatives. The newly synthesized compounds were characterized by various analytical and spectral techniques. In addition, their antimicrobial activity was evaluated as well as modeling studies were performed to investigate their ability to recognize and bind to the biotin carboxylase (BC)-active site. The results showed a broad spectrum antibacterial and antifungal profile of the synthesized derivatives. Docking results demonstrated that all members of this class of new derivatives were able to recognize the active site of Escherichia coli BC and form different types of bonding interactions with key active site amino acid residues. Besides the compounds with promising antimicrobial activity in addition to 6-aminothiouracil, as control, were incorporated into polycaprolactone nanoparticles to improve their water solubility, permeability through physiological barriers and consequently enhanced therapeutic efficacy. The compounds-loaded nanoparticles were prepared using single emulsion-solvent evaporation technique, and their diameters were found to be in the range 136 ± 30 to 213 ± 28 nm. Transmission electron microscopy (TEM) showed a spherical and dense morphology of the nanoparticles. The results also showed high entrapment efficiency of the synthesized bioactive compounds in the nanoparticles (85 ± 5% to 91 ± 2%) with a desirable in vitro biodegradation and release profiles.

6-trifluoromethyl-2-thiouracil possesses anti-Toxoplasma gondii effect in vitro and in vivo with low hepatotoxicity.

Since pyrimethamine, the general therapeutic drug for toxoplasmosis, presents several adverse side effects, the need to develop and evaluate new drugs for the condition is critical. In this study, anti-Toxoplasma gondii activities of 3-[{2-((E)-furan-2-ylmethylene)hydrazinyl}methylene]-1,3-dihydroindol-2-one (ATT-5126) and 6-trifluoromethyl-2-thiouracil (KH-0562) were evaluated in vitro using a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and in vivo by measuring amount of the tachyzoites in mice ascites. Biochemical parameters such as lipid peroxidation (LPO), glutathione (GSH), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were also evaluated in livers of mice at 4 days post-infection. As a result, the ATT-5126 and KH-0562 showed anti-T. gondii activity in vitro. Treatment of ATT-5126 or KH-0562 decreased the amount of tachyzoites in T. gondii infected ICR mice. The relative weight of liver and spleen increased by T. gondii infection were decreased by treatment of ATT-5126 or KH-0562. The levels of LPO, ALT and AST, which are biochemical parameters involved in liver injury, were also significantly recovered by treatment of ATT-5126 or KH-0562 (p<0.05). In particular, the recovered levels by KH-0562 were similar to those of pyrimethamine-treated group (p<0.05). However, the level of GSH, which is an antioxidant indicator, showed insignificant statistics. The results suggest that KH-0562 show anti-T. gondii activities in vitro and in vivo with low hepatotoxicity. Therefore, KH-0562 may be a useful candidate for treating T. gondii infection.

Effect of Cd, Zn and Hg complexes of barbituric acid and thiouracil on rat brain monoamine oxidase-B (in vitro).

Metal pyrimidine complexes (MPCs) including cadmium-barbiturate (Cd-BA), zinc-barbiturate (Zn-BA), cadmium-thiouracil (Cd-TU) and mercury-thiouracil (Hg-TU) were prepared and their analysis was carried out. These MPCs were evaluated as monoamine oxidase-B (MAO-B) inhibitors. Rat brain MAO-B was inhibited (in vitro) by Cd-BA, Zn-BA, Cd-TU and Hg-TU complexes. The inhibition of MAO-B by these complexes was time and concentration dependent. The values of IC50 of Zn-BA, Cd-BA, Hg-TU and Cd-TU were 10.2, 15.8, 16.2 and 20.4 nM, respectively. The effect of different substrate concentrations in the absence and in the presence of MPCs was determined. Lineweaver-Burk plots were plotted and the values of apparent Michaelis constant (Km), maximum velocity (Vmax), the dissociation constant of enzyme inhibitor complex (Ki) and the percent of inhibition (i%) were calculated. The data showed that the inhibition of MAO-B by all studied MPCs was the non-competitive type. The sequence of inhibition zone was: Zn-BA>Cd-BA and Hg-TU>Cd-TU affected by the chemistry of both the metal and the ligand. Otherwise, the results of the present study showed that the inhibition of MAO-B by all MPCs was fully reversible. The data showed that the presence of Cd-BA, Zn-BA, Cd-TU and Hg-TU complexes changed the optimum temperature and pH of MAO-B.

Synthesis, antimicrobial, antioxidant activities of novel 6-aryl-5-cyano thiouracil derivatives.

A series of 6-aryl-5-cyano thiouracil derivatives (2a-c to 11a-c) was synthesized from 6-aryl-4-hydrazino-2-thioxo-1,2-dihydropyrimidine-5-carbonitriles (1a-c). The products were characterized by analytical and spectral data (IR, (1)H NMR, (13)C NMR and mass spectra). All compounds were screened for their in-vitro antibacterial and antifungal activities. Compounds 7a, 7g and 9a-c showed pronounced antimicrobial activity than standards. Some of the newly synthesized compounds were evaluated for antioxidant activity. Compounds 1c, 5c and 8c displayed promising free radical scavenging activity and found to be more potent than standard, ascorbic acid (vitamin C).

Spectral and Eukaryotic DNA degradation studies for Ni(II), Pd(II), Pt(IV), Cu(II) and UO2(2+) complexes derived from thiouracil derivative.

A derivative of thiouracil ligand was prepared. Ni(II), Pd(II), Pt(IV), Cu(II) and UO2(2+) complexes were prepared. The elemental and different spectral tools were used for their characterization. A binegative tetradentate mode is the general coordination behavior of the ligand towards all metal ions used. The structural geometries were varied from square-planer (Pt, Pd(II)), square-pyramidal (Cu(II)) and octahedral (UO2(2+)). The geometry optimization implementing the hyperChem reveals that the Cu(II) complex is the most stable one. The thermogravimetric analysis supports the presence of solvent molecules attached with most complexes. The biological investigation was studied on different microorganisms as gram-positive, gram-negative and fungia. The Ni(II) complex shows the most toxic activity towards most organisms used. The degradation effect of DNA was studied by the use of investigated compounds and reveal that the Ni(II) and Pd(II) complexes are the most effective on the DNA degradation.

Coordination modes, spectral, thermal and biological evaluation of hetero-metal copper containing 2-thiouracil complexes.

Mononuclear copper complex [CuL(NH(3))(4)]Cl(2)·0.5H(2)O and three new hetero-metallic complexes: [Cu(2)Ni(L)(2)(NH(3))(2)Cl(2)·6H(2)O] 2H(2)O(,) [Cu(3)Co(L)(4)·8H2O]Cl·4(·)5H(2)O, and [Cu(4)Co(2)Ni(L)(3)(OH)(4)(NH(3))Cl(4)·3H(2)O]4H(2)O where L is 2-thiouracil, were prepared and characterized by elemental analyses, molar conductance, room-temperature magnetic susceptibility, spectral (IR, UV-Vis and ESR) studies and thermal analyses techniques (TG, DTG and DTA). The molar conductance data revealed that [CuL(NH(3))(4)]Cl(2)·0.5H(2)O and [Cu(3)Co(L)(4)·8H2O]Cl·4.5H(2)O are electrolytes, while, [Cu(2)Ni(L)(2)(NH(3))(2)Cl(2·)6H(2)O]·2H(2)O and [Cu(4)Co(2)Ni(L)(3)(OH)(4)(NH(3))Cl(4)·3H(2)O]4H(2)O are non-electrolytes. IR spectra showed, that 2-thiouracil ligand behaves as a bidentate or tetradentate ligand. The geometry around the metal atoms is octahedral in all the prepared complexes except in [Cu(4)Co(2)Ni(L)(3)(OH)(4)(NH(3))Cl(4)·3H(2)O]4H(2)O complex where square planar environment around Co(II), Ni(II) and Cu(II) were suggested. Thermal decomposition study of the prepared complexes was monitored by TG, DTG and DTA analyses under N(2) atmosphere. The decomposition course and steps were analyzed. The order of chemical reactions (n) was calculated via the peak symmetry method and the activation parameters of the non- isothermal decomposition were computed from the thermal decomposition data. The negative values of ΔS(∗) deduced the ordered structures of the prepared complexes compared to their starting reactants. The antimicrobial activity of the prepared complexes were screened in vitro against a Gram positive, a Gram negative bacteria, a filamentous fungi and a yeast. The antimicrobial screening data showed that the studied compounds exhibited a good level of activity against Escherichia coli, Staphylococcus aureus and Candida albicans but have no efficacy against Aspergillus flavus. It was observed that [Cu(4)Co(2)Ni(L)(3)(OH)(4)(NH(3))Cl(4)·3H(2)O]4H(2)O complex showed the most intensive activity against the tested microorganisms. Trials to prepare single crystals from complexes were failed.