Thiazole Ring Research Articles

Characterization, theoretical investigation, and biological applications of Mn(II), Co(II), Ni(II), Cu(II), and Zn(II) complexes of a triazene ligand containing a benzothiazole ring

AbstractHerein, Mn(II), Co(II), Ni(II), Cu(II), and Zn(II) complexes of a previously synthesized triazene ligand, namely, (E)‐2‐(3‐(4‐nitrophenyl)triaz‐1‐en‐1‐yl)benzo[d]thiazole (L), were prepared. The metal:ligand ratio of complexes was determined by molar ratio method, and complexes were synthesized based on the result ratio (1:2 for Co(II), Ni(II), and Zn(II) complexes, and (1:1) for Cu(II) and Mn(II)). The complexes were characterized by infrared (IR) and electron paramagnetic resonance (EPR) spectroscopies, magnetic moment, and/or molar conductance measurements. IR spectra suggested the existence of bidentate binding through the nitrogen atom of the thiazole ring and nitrogen atom of the triazene linkage. Molar conductivities indicated the non‐electrolytic nature of all the complexes. Magnetic moment and EPR of the complexes confirmed their octahedral geometries. Thermal studies were conducted to confirm the structures and analyze the thermal stabilities of the complexes. Activation thermodynamic parameters were determined using the Coats–Redfern and Horowitz–Metzger methods. The calf thymus DNA binding activity was investigated by absorption titration experiments and viscosity measurements, and intrinsic binding constants of complexes range from 4.00 × 105 to 5.00 × 105 M−1. Cytotoxic activities were examined against MCF‐7 and HCT‐116 cell lines. Although all the complexes exhibited reasonable cytotoxic effects, their cytotoxic activities were in the following order: Zn(II) > Cu(II) > Mn(II) > Co(II) > Ni(II). Zn(II) complex showed the highest activity with IC50 values are 2.87 and 1.94 μg ml−1 against MCF‐7 and HCT‐116, respectively. Molecular docking was used to assess the binding affinities of these complexes to colon cancer (3ig7) and breast cancer (1hk7) proteins. Zn(II) complex showed the best docking scores compared with the ligand and other tested complexes. Results of molecular docking well correlated with those of the cytotoxicity experiments.

Structural, surface, and computational analysis of two vitamin-B1 crystals with sulfonimide-based anions

Abstract Two crystals incorporating the thiamine·HCl cation and the fluorinated anion 1,3-disulfonylhexafluoropropyleneimide have been characterized via single-crystal X-ray diffraction. The host-guest interactions of thiamine with the anions are analyzed and characterized using Hirshfeld surface analysis. The cations in both structures form a dimer in the solid-state via reciprocal hydrogen bonding through the amine and hydroxyl moieties. Additional investigation into the interactions responsible for dimer formation found that the sulfur atom in the thiazolium ring interacting with several hydrogen atoms to form stabilizing interactions. These interactions in the dimer are further analyzed using reduced density gradient analysis and the results are correlated to the fingerprint plots derived from the Hirshfeld surfaces. Moreover, specific interactions are observed from the cyclical anions, with both the fluorine and sulfonyl oxygen atoms participating in bridging interactions, displaying the diverse host-guest properties of thiamine.

Anticancer Activity and In Silico ADMET Properties of 2,4,5-Trisubstitutedthiazole Derivatives.

Recently, a series of 15 compounds with 2,4,5-trisubstitutedthiazole scaffold having 2- amino/amido/ureido functional groups attached with 5-aryl and 4-carboxylic acid/ester groups (1-15) were reported from our research group as novel potential inhibitors of carbonic anhydrase III (CA III) enzyme. Several research studies revealed the potential role of CA inhibitors as anticancer agents, giving us the impetus to further explore these compounds for their potential as anticancer agents. The objective of this study is to investigate the potential of 2,4,5-trisubstitutedthiazole derivatives (1-15) for their possible cytotoxic activity (in vitro), and to calculate (in silico) the absorption, distribution, metabolism, excretion and toxicity (ADMET) properties to evaluate the drug-likeness of these compounds. Cytotoxic activity (in vitro) was carried out on two breast cancer cell lines (MCF7 and MDA231), and the lymphoblastoid human erythroleukemia cell line (K562) using 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay. Doxorubicin was used as a positive control. ADMET properties were calculated (in silico) using the QikProp module of Schrodinger. Compounds 6 and 9 with a phenylureido group at 2-position, and a methyl-carboxylate moiety at 4-position having para-tolyl and benzyl moiety, respectively at the 5-position of the thiazole ring showed significant cytotoxicity against all the three cell lines. In particular, compound 6 with para-tolyl group at 5-position exhibited the most potent inhibitory effect on the viability of MCF7, MDA231 and K562 cells, with IC50 values of 22, 26 and 11 μM, respectively. Notably, all the highly active compounds possess a phenyluriedo group at 2-- position with a methyl ester group at 4-position, indicating the probable role of these substituents in the target interaction and inducing cytotoxicity. Interestingly, compounds 1-4 and 10-13 with a free amino group at 2-position did not show any cytotoxic effect on the K562 cell line, while exhibiting mild to moderate cytotoxicity against the MCF7 and MDA231 cell lines. However, none of the tested compounds showed any activity against normal human dermal fibroblast cells indicating the safety/tolerability of the examined concentrations. Furthermore, these compounds also exhibited satisfactory ADMET properties (in silico), without violating Lipinski's rule of five. The most active compounds 6 and 9 predicted to have good oral absorption and low human serum protein binding, exhibiting no reactive functional group and probable CNS activity compared with 95% of the known oral drugs as predicted (in silico) by QikProp. Thus, compounds 6 and 9 can be considered as lead molecules for further modification and discovery of novel anticancer agents with nanomolar potency.

Hydrazonoyl bromide precursors as DHFR inhibitors for the synthesis of bis-thiazolyl pyrazole derivatives; antimicrobial activities, antibiofilm, and drug combination studies against MRSA

Microbial resistance is a big concern worldwide, making the development of new antimicrobial drugs difficult. The thiazole and pyrazole rings are important heterocyclic compounds utilized to produce a variety of antimicrobial medications. As a result, a series of new bis-thiazolyl-pyrazole derivatives 3, 4a-c, 5a, b, and 6a-c was synthesized by reacting bis hydrazonoyl bromide with several active methylene reagents in a one-pot reaction. The assigned structure was characterized entirely based on elemental and spectral analyses. The antimicrobial activity represented by MIC was performed using a resazurin-based turbidimetric (TB) assay. The results exhibited good antimicrobial activity against gram-positive strains, especially S. aureus (ATCC6538) while showing poor to moderate activity against gram-negative and fungal strains. Furthermore, the most active derivatives 3, 4a, 4c, and 5b were evaluated for MIC, MBC, antibiofilm, hemolytic assay, and drug combination testing against two S. aureus (ATCC6538) and MRSA (ACL18) strains. Additionally, bis-thiazolyl pyrazole 3, 4c, and 5b exhibited more potent inhibitory activity for DHFR with IC50 values (6.34 ± 0.26, 7.49 ± 0.28, and 3.81 ± 0.16 µM), respectively, compared with Trimethoprim (8.34 ± 0.11 µM). The bis-1-(substituted-thiazol-2-yl)-1H-pyrazole-4-carbonitrile derivative 5b was the most active member with MIC values ranging from (0.12–0.25 µM) compared to Vancomycin (1–2 µM), and MBC values ranging from (0.5–1 µM) for S. aureus (ATCC6538) and MRSA (ACL18). Surprisingly, compound 5b displayed bactericidal behavior, synergistic effect with three commercial antibiotics, and inhibited DHFR with 2.1 folds higher than Trimethoprim. Finally, good findings were obtained from in silico investigations incorporating toxicity prediction and molecular docking simulation.

Complex of Ca(II) with Ceftriaxone: Synthesis, Structure, Spectral and Antibacterial Properties

The calcium complex of ceftriaxone was synthesized and characterized by elemental, atomic-emission analysis, TGA, IR spectroscopy and density functional theory calculations. The luminescence and antibacterial properties of the ceftriaxone disodium and calcium complex were investigated. Ca(II) complex was obtained in a crystalline form, cell parameters of the compound were determined. Ceftriaxone was coordinated to the calcium ion by the oxygen of the triazine cycle in the 6th position, the nitrogen of the amine group of the thiazole ring, and the oxygens of the lactam carbonyl and carboxylate groups. The complex of Ca(II) with ceftriaxone was screened for antibacterial activity against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa, and the results were compared with the activity of ceftriaxone disodium salt

STUDY OF THE BIOLOGICAL PROPERTIES OF SEMI- AND THIOSEMICARBAZONES OF CARBONYL DERIVATIVES OF 4-BUTANOLIDES

Based on carbonyl derivatives of 4-substituted-4-butanolides, the appropriate semi- and thiosemicarbazones have been synthesized. It has been found that some representatives of thiosemicarbazones have pronounced algicidal activity against filamentous green alga Cladophora and blue-green alga (cyanobacterium) Synechocystis and some of the semi- and thiosemicarbazones exhibit moderate antitumor activity. The assessment of the antitumor activity of the compounds was carried out using strains of syngeneic and allogeneic tumor systems as test-objects: lymphocytic leukemia P-388, Lewis lung carcinoma, B16 melanoma and Ehrlich’s ascites tumor. It has also been established that some representatives of thiosemi­carbazones exhibit antimutagenic properties. It has been reliably proven that with the formation of a thiazole ring, all properties disappear and a new property in the series of thiazololactones is revealed – antibacterial․

Synthesis and Identification of some new Derivatives Oxazole, Thiazole and Imidazol from Acetyl Cysteine

Some fused heterocyclic oxazoles and imidazols rings were synthesized from reaction of N- acetyl cysteine with different treatment. After thiol group protection, N-acetyl-S-ethyl cysteine (2) had been esterified to give ester 3 which cyclized to oxazole 4 with phosphorus oxychloride. N-acetyl-S-ethyl cysteine 2 were converted to acid chloride 5 with thionyle chloride. Amide 6 were synthesized from 5 with ammonia solution. Amide 6 converted to substituted carbamide 7 by react with P2S5, then the product reacted with α-chloroacetophenone to give substituted thiazol ring 8 that converted to bicyclic thiazole – imidazole ring system 9. Cyclized benzoxazole derivative 10 had been synthesized then converted to 3-(ethylthio)-1-methyl-1,3a-dihydrobenzo[d]imidazo[5,1-b]oxazole (11). Structure of new synthesized compounds were confirms by IR ,1H-NMR, and UV spectra as well as physical constant.

Synthesis, characterization, biological evaluation, and molecular docking approach of nickel (II) complexes containing O, N‐donor chelation pattern of sulfonamide‐based Schiff bases

AbstractA series of Schiff bases (L1–L4) that possess in their structure bioactive sulfonamide group and their nickel (II) complexes have been synthesized. Microanalytical analyses, various spectroscopic methods such as Fourier transform infrared spectroscopy (FT‐IR), 1H nuclear magnetic resonance (NMR), 13C NMR, UV–Vis, and MS, are used to explore the nature of bonding and to elucidate the chemical structures. The analytical and magnetic values suggest a range of stoichiometries 1:1, 1:2, and 2:1 (M:L) for the synthesized complexes of almost square planar geometry. The spectral comparative interpretation reveals that L1 and L2 coordinate to the central Ni (II) in tetradentate ONON donor sequence, whereas L3 and L4 in bidentate ON pattern through deprotonated phenolic‐O and the azomethine‐N. Density functional theory (DFT) and MOE‐docking approaches are used to evaluate the molecular parameters and the binding propensity of the synthesized ligands and their complexes with 3s7s protein and to signify their inhibition strength. Besides, the anticancer, antimicrobial and antifungal activities have been screened against number of tumor cells and human pathogen strains. These in vitro studies reveal that Schiff base L4 and its complex, [Ni(L4‐H)(OAc)(H2O)], have superior activities reflecting the importance of inserting bioactive pendant substituents such as thiazole ring and 3‐fluorophenylazo to the pharmacophoric sulfonamide moiety. Moreover, some of the synthesized Ni (II) complexes display promising therapeutic effects as novel non‐platinum antitumor agents after further preclinical investigations.

Molecular modeling and antioxidant evaluation of new di-2-thienyl ketones festooned with thiazole or pyridine moiety

• Synthesis of new functionalized dithienyl ketones linked thiazole and/or pyridine. • The DFT study was conducted to determine the HOMO-LUMO energies and Fukui's indices. • The local relative electrophilicity and nucleophilicity descriptors were calculated. • Antioxidant activity of the synthesized dithienyl ketone derivatives was explored. • The computational docking processes were examined toward (PDB Code: 2AS1). Different novel derivatives of 5-(5-bromothiophen-2-oyl)-2-(phenylamino)thiophen-3-yl) ethylidene-hydrazinylthiazole and 2-(5-bromothiophen-2-oyl)thieno[2,3-b]pyridine were prepared by utilizing the synthesized (5-bromothien-2-yl) (4-acetyl-3-methyl-5-phenylaminothien-2-yl) ketone (3) as a precursor. The electronic and chemical reactivity of the derivatives toward nucleophilic, electrophilic, and radical attacks were evaluated based on quantum chemical calculations; the highest occupied molecular orbital (HOMO)-lowest occupied molecular orbital (LUMO) energies and Fukui indices were determined using the density functional theory (DFT) at Becke, 3-parameter, Lee–Yang–Parr (B3LYP) level. Compound 6 possessed the lowest HOMO energy value (E H ), LUMO energy value (E L ), and energy gap (ΔE H-L ). Significant inhibition percentage was observed while evaluating the antioxidant activities of the synthesized di-2-thienyl ketones 3–8 using vitamin C as a reference drug. The highest antioxidant activity with an IC 50 value of 39.85 and 34.37 µM was observed for the di-2-thienyl ketones 5 and 6 incorporating thiazole ring. Meanwhile, the rest of the di-2-thienyl ketone derivatives displayed reasonable IC 50 values from 51.60 to 68.88 µM. This experimental data was supported by molecular docking analysis of the interactions between di-2-thienyl ketone compounds and cytochrome c peroxidase (PDB Code: 2AS1) applied through Molecular Operating Environment (MOE) v10.2015.10.

Novel 2-(Adamantan-1-ylamino)Thiazol-4(5H)-One Derivatives and Their Inhibitory Activity towards 11β-HSD1-Synthesis, Molecular Docking and In Vitro Studies.

A common mechanism in which glucocorticoids participate is suggested in the pathogenesis of such metabolic diseases as obesity, metabolic syndrome, or Cushing’s syndrome. The enzyme involved in the control of the availability of cortisol, the active form of the glucocorticoid for the glucocorticoid receptor, is 11β-HSD1. Inhibition of 11β-HSD1 activity may bring beneficial results for the alleviation of the course of metabolic diseases such as metabolic syndrome, Cushing’s syndrome or type 2 diabetes. In this work, we obtained 10 novel 2-(adamantan-1-ylamino)thiazol-4(5H)-one derivatives containing different substituents at C-5 of thiazole ring and tested their activity towards inhibition of two 11β-HSD isoforms. For most of them, over 50% inhibition of 11β-HSD1 and less than 45% inhibition of 11β-HSD2 activity at the concentration of 10 µM was observed. The binding energies found during docking simulations for 11β-HSD1 correctly reproduced the experimental IC50 values for analyzed compounds. The most active compound 2-(adamantan-1-ylamino)-1-thia-3-azaspiro[4.5]dec-2-en-4-one (3i) inhibits the activity of isoform 1 by 82.82%. This value is comparable to the known inhibitor-carbenoxolone. The IC50 value is twice the value determined by us for carbenoxolone, however inhibition of the enzyme isoform 2 to a lesser extent makes it an excellent material for further tests.

The synergistic role of azomethine group and triazole ring at improving the anti-corrosive performance of 2-amino-4-phenylthiazole

2-Amino-4-phenyl-N-benzylidene-5-(1,2,4-triazol-1-yl)thiazole (APNT) and 2-amino-4-phenylthiazole (APT) were selected as the investigated subject to study the effect of replacement and addition on the corrosion inhibitory efficiency of mild steel in a 1 M HCl environment. Experimental results from weight loss techniques show that the substitution of triazoles in the thiazole ring, as well as the addition of benzildine to the amino group, increases the anti-corrosion efficacy of APNT (98.1%), which is higher than that of ATP (94.7%) with the same reaction conditions, the concentration (500 ppm) of the corrosion inhibitor, as well as the temperature (303 K) of the solution and the exposure period (5 h). The experimental results exhibit that increasing the APNT and APT concentrations will improve the inhibition efficiency. The experimental findings obtained from weight loss measurements are dependent on the interpretation of the scanning electron microscopy photographs. The adsorption of APNT or APT molecules on the mild steel surface followed Langmuir adsorption model. Moreover, the quantum chemical demonstrate that the substitution of a triazole in the thiazole ring and also the addition of benzylidene in the APNT are the adsorption sites, and increase the interaction of the APNT molecules with the iron atoms on the surface of mild steel.. A comparative theoretical study of APNT and APT molecules, as corrosion inhibitors were performed using density functional theory (DFT) with the B3LYP functional basis set. Density functional theory (DFT) data have illustrated the mechanism of adsorption of APNT as tested inhibitor on the mild steel surface.

Synthesis and cytostatic activity of emissive 7-thiazolyl-7-deazapurine nucleosides

7-Functionalized 7-deazapurine fluorescent nucleosides are highly important for biotechnological applications. Here, 7-substituted 7-deaza-2′-deoxyguanosines, comprising a 4H-cyclopenta[d]thiazole ring are obtained by Hantzsch synthesis reaction of 7-thioamide-7-deaza-2′-deoxyguanosine with aromatic α-bromocarbonyl compounds (61–85%). Their photophysical properties are determined by UV and fluorescence spectroscopy, and the cytostatic activities are evaluated by MTT assay. All compounds exhibit strong solvatochromicity and pH-dependent fluorescence in aqueous solutions, indicating their promising ability to be fluorescent probes. The 7-substituted 7-deaza-2′-deoxyguanosines 5a, 5i and 5j exert cytostatic activities, which means they have the potential to be candidate for theranostics.

Design, synthesis, in vitro and in silico studies of some novel thiazole-dihydrofuran derivatives as aromatase inhibitors

Aromatase inhibitors used against hormone-dependent breast cancer, especially in post-menopausal women, are very susceptible to the development of resistance due to their limited number and long-term use. In this study, it is aimed to obtain new aromatase inhibitors including thiazole and dihydrofuran ring systems. Synthesis of compounds (2a-2l) were performed according to literature methods. Their structures were elucidated by 1H NMR, 13C NMR and APCI-MS spectroscopic methods. MTT test was carried out to assess the cell proliferation effects of the different compounds on two different pulmonary cell lines (A549, CCD-19Lu) and mammary cell line (MCF7). According to MTT assay, it was observed that the calculated IC50 values of some compounds for the CCD-19Lu cell line were found higher than for the A549 and MCF7 cell lines. Considering the viability results, it was found that the selected compounds (2a, 2c, 2e, 2g, 2h, 2l) showed favourable safety profile and have anticancer activities. Apoptotic activities of the selected compounds were investigated by flow cytometry analysis. And were found that have apoptotic effects on cancerous cell lines. In the light of this information, the aromatase inhibition potentials of 2g and 2l compounds, which are the most active derivatives, were examined in vitro and it was determined that they showed a similar inhibition profile with letrazole. Interaction modes between aromatase enzyme and compounds 2g and 2l were investigated by docking studies. In conclusion, findings of these study indicate that compounds 2g and 2l possess significant anticancer activity.

Structural improvement of new thiazolyl-isatin derivatives produces potent and selective trypanocidal and leishmanicidal compounds

Neglected diseases are a group of transmissible diseases that occur mostly in countries in tropical climates. Among this group, Chagas disease and leishmaniasis stand out, considered threats to global health. Treatment for these diseases is limited. Therefore, there is a need for new therapies against these diseases. In this sense, our proposal consisted of developing two series of compounds, using a molecular hybridization of the heterocyclic isatin and thiazole. The isatin and thiazole ring are important scaffold for several biological disorders, including antiparasitic ones. Herein, thiazolyl-isatin has been synthesized from respective thiosemicarbazone or phenyl-thiosemicarbazone, being some of these new thiazolyl-isatin toxic for trypomastigotes without affecting macrophages viability. From this series, compounds 2e (IC50 = 4.43 μM), 2j (IC50 = 2.05 μM), 2l (IC50 = 4.12 μM) and 2m (1.72 μM) showed the best anti-T. cruzi activity for trypomastigote form presenting a selectivity index higher than Benznidazole (BZN). Compounds 2j, 2l and 2m were able to induce a significantly labelling compatible with necrosis in trypomastigotes. Analysis by scanning electron microscopy showed that T. cruzi trypomastigote cells treated with the compound 2m from IC50 concentrations, promoted changes in the shape, flagella and surface of body causing of the parasite dead. Concerning leishmanicidal evaluation against L. amazonensis and L. infantum, compounds 2l (IC50 = 7.36 and 7.97 μM, respectively) and 2m (6.17 and 6.04 μM, respectively) showed the best activity for promastigote form, besides showed a higher selectivity than Miltefosine. Thus, compounds 2l and 2m showed dual in vitro trypanosomicidal and leishmanicidal activities. A structural activity relationship study showed that thiazolyl-isatin derivatives from phenyl-thiosemicarbazone (2a-m) were, in general, more active than thiazolyl-isatin derivatives from thiosemicarbazone (1a-g). Crystallography studies revealed a different configuration between series 1a-g and 2a-m. The configuration and spatial arrangement divergent between the two sub-series could explain the improved biological activity profile of 2a-m sub-series.

Design and synthesis of novel 2,4,5-thiazole derivatives as 6-APA mimics and antimicrobial activity evaluation

Nine new thiazole derivatives were synthesized considering 6-acetyl penicillanic acid (6-APA) and investigated for their antimicrobial activity. Ethyl 2-(2-mercaptoacetamido)-4-methylthiazole-5-carboxylate derivatives (3a–3i) were gained with a two-step synthetic method using conventional Hantzsch thiazole synthesis. The structural elucidation of the compounds was performed by 1H-NMR, 13C-NMR spectral data and HRMS. All compounds were tested on eleven bacteria and sixteen fungi species and minimum inhibitory concentration (MIC) was determined for each. Compounds 3d (4-methyl-2-(2-((5-methyl-1,3,4-thiadiazol-2-yl), 3f (4-methyl-2-(2-((5-nitro-1H-benzimidazol-2-yl) and 3g (4-methyl-2-(2-((5-methyl-4H-1,2,4-triazol-3-yl) bearing thiazole, 5-nitrobenzimidazole and triazole rings respectively exhibited high antimicrobial activity against most of the strains. In silico physicochemical properties were calculated for the compounds and it was detected that they comply with the rules of drug availability.

Novel Triarylamine-Based Hole Transport Materials: Synthesis, Characterization and Computational Investigation.

Three novel triarylamine-based electron-rich chromophores were synthesized and fully characterized. Compounds 1 and 2 were designed with electron-rich triphenylamine skeleton bearing two and four decyloxy groups namely, 3,4-bis(decyloxy)-N,N-diphenylaniline and N-(3,4-bis(decyloxy)phenyl)-3,4-bis(decyloxy)-N-phenylaniline, respectively. The well-known electron-rich phenothiazine was introduced to diphenylamine moiety through a thiazole ring to form N,N-bis(3,4-bis(decyloxy)phenyl)-5-(10H-phenothiazin-2-yl)thiazol-2-amine (Compound 3). These three novel compounds were fully characterized and their UV–vis absorption indicated their transparency as a favorable property for hole transport materials (HTMs) suitable for perovskite solar cells. Cyclic voltammetry measurements revealed that the HOMO energy levels were in the range 5.00–5.16 eV for all compounds, indicating their suitability with the HOMO energy level of the perovskite photosensitizer. Density functional theory (DFT) and time-dependent DFT (TD-DFT) have been used to investigate the possibility of the synthesized compounds to be utilized as HTMs for perovskite solar cells (PSCs). The computational investigation revealed that the hole mobility of Compound 1 was 1.08 × 10−2 cm2 V−1 s−1, and the substitution with two additional dialkoxy groups on the second phenyl ring as represented by Compound 2 significantly boosted the hole mobility to reach the value 4.21 × 10−2 cm2 V−1 s−1. On the other hand, Compound 3, in which the third phenyl group was replaced by a thiazole-based phenothiazine, the value of hole mobility decreased to reach 5.93 × 10−5 cm2 V−1 s−1. The overall results indicate that these three novel compounds could be promising HTMs for perovskite solar cells.

Synthesis and Antinociceptive Effect of Some Thiazole-Piperazine Derivatives: Involvement of Opioidergic System in the Activity

In this study, we aimed to design and synthesize novel molecules carrying both the thiazole and piperazine rings in their structures and to investigate their antinociceptive activity. Targeted compounds were obtained by reacting thiosemicarbazide derivative and appropriate 2-bromoacetophenone in ethanol. The structures of the obtained compounds were determined using data from various spectroscopic methods (IR, 1H-NMR, 13C-NMR, and LCMSMS). Experimental data from in vivo tests showed that test compounds 3a–3c, 3f, and 3g (50 mg/kg) significantly prolonged reaction times of animals in tail-clip and hot-plate tests compared to the controls, indicating that these compounds possess centrally mediated antinociceptive activities. Furthermore, these compounds reduced the number of writhing behaviors in the acetic acid-induced writhing tests, showing that the compounds also possess peripheral antinociceptive activity. In the mechanistic studies, naloxone pre-treatments abolished the antinociceptive activities of compounds 3a–3c, 3f, and 3g, indicating that opioidergic mechanisms were involved in their antinociceptive effects. Molecular docking studies demonstrating significant interactions between the active compounds and µ- and δ-opioid receptor proteins supported the pharmacological findings. This study is the first showing that molecules designed to bear thiazole and piperazine moieties together on their structure exert centrally and peripherally mediated antinociceptive effects by activating the opioid system.

Synthesis, cytotoxicity assessment and antioxidant activity of some new thiazol‐2‐yl carboxamides

AbstractDependence on the biological activity of 2‐aminothiazole, the synthesis and chemical reactions of ethyl 3‐oxo‐3‐(thiazol‐2‐ylamino)propanoate (1) with some different reagents were described for cytotoxic and antioxidant evaluation. The new derivatives 2–19 could be synthesized and characterized by correct analytical and spectral data. In addition to the thiazole ring, these compounds contain 2H‐1,2,3‐triazole (3), 1H‐pyrazole (5, 12), 1,3‐dithiane (7), benzothiazole (10), thiazolidine (13), thiazolidinone (14, 15), 2H‐chromene (17), pyridine (19) moieties. The preparation of compounds 2–19 was performed through the formation of the isolable 2‐(2‐phenylhydrazineylidene) 2, 2‐dimethylaminomethylidene 4, 2‐phenylcarbamothioyl 9, 2‐(methylthio)(phenylamino) methylidene 11 and non‐isolable potassium bis(thiolate) 6, potassium thiolate 8 intermediates from precursor 1. The activity of these derivatives 1–19 against human lung fibroblast (WI38) and human prostate cancer (PC3) were examined in vitro using the MTT assay. The assessment of their antioxidant activities was carried out by following the ABTS method to evaluate their pharmaceutical importance.

Thiazole Ring-A Biologically Active Scaffold.

Background: Thiazole is a good pharmacophore nucleus due to its various pharmaceutical applications. Its derivatives have a wide range of biological activities such as antioxidant, analgesic, and antimicrobial including antibacterial, antifungal, antimalarial, anticancer, antiallergic, antihypertensive, anti-inflammatory, and antipsychotic. Indeed, the thiazole scaffold is contained in more than 18 FDA-approved drugs as well as in numerous experimental drugs. Objective: To summarize recent literature on the biological activities of thiazole ring-containing compounds Methods: A literature survey regarding the topics from the year 2015 up to now was carried out. Older publications were not included, since they were previously analyzed in available peer reviews. Results: Nearly 124 research articles were found, critically analyzed, and arranged regarding the synthesis and biological activities of thiazoles derivatives in the last 5 years.

Neuroprotective Effects of Thiamine and Precursors with Higher Bioavailability: Focus on Benfotiamine and Dibenzoylthiamine.

Thiamine (vitamin B1) is essential for brain function because of the coenzyme role of thiamine diphosphate (ThDP) in glucose and energy metabolism. In order to compensate thiamine deficiency, several thiamine precursors with higher bioavailability were developed since the 1950s. Among these, the thioester benfotiamine (BFT) has been extensively studied and has beneficial effects both in rodent models of neurodegeneration and in human clinical studies. BFT has antioxidant and anti-inflammatory properties that seem to be mediated by a mechanism independent of the coenzyme function of ThDP. BFT has no adverse effects and improves cognitive outcome in patients with mild Alzheimer’s disease (AD). Recent in vitro studies show that another thiamine thioester, dibenzoylthiamine (DBT) is even more efficient that BFT, especially with respect to its anti-inflammatory potency. Thiamine thioesters have pleiotropic properties linked to an increase in circulating thiamine concentrations and possibly in hitherto unidentified metabolites in particular open thiazole ring derivatives. The identification of the active neuroprotective derivatives and the clarification of their mechanism of action open extremely promising perspectives in the field of neurodegenerative, neurodevelopmental and psychiatric conditions.