Search

Macrocyclic peptides containing a thiazole or thiazoline in the backbone are considered privileged structures in both natural compounds and drug discovery, owing to their enhanced bioactivity, stability, and permeability. Here, we present the biocompatible synthesis of macrocyclic peptides from N‐terminal cysteine and C‐terminal nitrile. While the N‐terminal cysteine is incorporated during solid‐phase peptide synthesis, the C‐terminal nitrile is introduced during cleavage with aminoacetonitrile, utilizing a cleavable benzotriazole linker. This method directly yields the fully functionalized linear peptide precursor. The biocompatible cyclization reaction occurs in buffer at physiological pH and room temperature. The resulting thiazoline heterocycle remains stable in buffer but hydrolyzes under acidic conditions. While such hydrolysis enables access to macrocyclic peptides with a complete amide backbone, mild oxidation of the thiazoline leads to the stable thiazole macrocyclic peptide. While conventional oxidation strategies involve metals, we developed a protocol simply relying on alkaline salt and air. Therefore, we offer a rapid and metal‐free pathway to macrocyclic thiazole peptides, featuring a biocompatible key cyclization step. [ABSTRACT FROM AUTHOR]

Melanoma is the most aggressive and lethal type of skin cancer due to its characteristics such as high metastatic potential and low response rate to existing treatment modalities. In this way, new drug prototypes are being studied to solve the problem of treating patients with melanoma. Among these, ruthenium-based metallopharmaceuticals may be promising alternatives due to their antitumor characteristics and low systemic toxicity. In this context, the present study evaluated the antineoplastic effect of the ruthenium complex [Ru(mtz)(dppe)2]PF6-2-mercaptothiazoline-di-1,2-bis(diphenylphosphine) ethaneruthenium(II), namely RuMTZ, on human melanoma (A-375) and murine (B16-F10) cells, considering different approaches. Through XTT colorimetric and clonogenic efficiency assays, the complex revealed the selective cytotoxic activity, with the lowest IC50 (0.4 µM) observed for A375 cells. RuMTZ also induced changes in cell morphology, increased cell population in the sub-G0 phase and inhibiting cell migration. The levels of γH2AX and cleaved caspase 3 proteins were increased in both cell lines treated with RuMTZ. These findings indicated that the cytotoxic activity of RuMTZ on melanoma cells is related, at least in part, to the induction of DNA damage and apoptosis. Therefore, RuMTZ exhibited promising antineoplastic activity against melanoma cells. [ABSTRACT FROM AUTHOR]

Simple Summary: The anticancer effects reported in several heterocyclic derivatives of thiadiazole and thiazoline prompted us to construct functionalized new carbohydrate heterocycle entities and investigate their potential anticancer effects on several cancer cells. Here, we show that two novel heterocyclic moieties linked to functionalized carbohydrate with an anhydro scaffold skeleton caused the death of the investigated cancer cells. Interestingly, both N-adducts augmented the cytostatic effect on several cancer cell lines with totally different mechanisms of action. The thiazoline derivative responds via apoptosis through caspase activation and the thiadiazole derivative responds through oxidative stress, DNA damage, and necrosis at the micromolecular level. The conjugate N-adducts of thio-1,3,4-diazole and 2-thiazoline with levoglucosenone were synthesized via a stereoselective, base-catalyzed conjugate N-Michael addition to levoglucosenone at C-4. Structural assignments were established using 1H and 13C NMR analysis, and X-ray single-crystal analysis for one of the compounds. The biological properties of the novel compounds were tested on a cell model. Cytotoxicity was analyzed via colorimetric assay. Two distinct types of cell death, apoptosis and necrosis, were analyzed by determining the phosphatidylserine levels from the outer leaflet of the plasma membrane, caspase activation, and lactate dehydrogenase release. We also evaluated DNA damage using an alkaline comet assay. The level of oxidative stress was measured with a modified comet assay and an H2DCFDA probe. The thio-1,3,4-diazole adduct (FCP23) and the 2-thiazoline adduct (FCP26) exhibit similar cytotoxicity values for cancer cells (ovarian (A2780), breast (MCF-7), cervix (HeLa), colon (LoVo), and brain (MO59J and MO59K)), but their mechanism of action is drastically different. While FCP23 induces oxidative stress, DNA damage, and necrosis, FCP26 induces apoptosis through caspase activation. [ABSTRACT FROM AUTHOR]

Wir präsentieren die erste Totalsynthese der Thiamyxine A–C und des jetzt vollständig charakterisierten Thiamyxins E, einer interessanten Klasse thiazol‐ und thiazolinreicher Depsipeptide mit vielfältiger antiviraler Aktivität. Die Synthese zeichnet sich aus durch einen parallelen Ringschluss zu zwei Methylthiazolin‐Einheiten unter geringer Epimerisierung des sehr labilen benachbarten stereogenen Zentrums. Des Weiteren wird die dreistufige Synthese einer ungewöhnlichen Hydroxysäure sowie die oxidationsfreie Eliminierung eines Phenylselenids zum Dehydroalanin gezeigt. Die Ausnutzung des säurelabilen Stereozentrums am Isoleucin‐Rest und die erneute Öffnung der Makrolactone ermöglichen den Zugang zu den vier Thiamyxinen in guten Ausbeuten und Diastereomerenverhältnissen aus einem einzigen Vorläufer. Durch die modular gestaltete Totalsynthese sind weitere Bioaktivitätstests und die Erforschung eines Pharmakophors über die Synthese weiterer Derivate möglich. [ABSTRACT FROM AUTHOR]

The conjugate N-adducts of thio-1,3,4-diazole and 2-thiazoline with levoglucosenone were synthesized via a stereoselective, base-catalyzed conjugate N-Michael addition to levoglucosenone at C-4. Structural assignments were established using 1H and 13C NMR analysis, and X-ray single-crystal analysis for one of the compounds. The biological properties of the novel compounds were tested on a cell model. Cytotoxicity was analyzed via colorimetric assay. Two distinct types of cell death, apoptosis and necrosis, were analyzed by determining the phosphatidylserine levels from the outer leaflet of the plasma membrane, caspase activation, and lactate dehydrogenase release. We also evaluated DNA damage using an alkaline comet assay. The level of oxidative stress was measured with a modified comet assay and an H2DCFDA probe. The thio-1,3,4-diazole adduct (FCP23) and the 2-thiazoline adduct (FCP26) exhibit similar cytotoxicity values for cancer cells (ovarian (A2780), breast (MCF-7), cervix (HeLa), colon (LoVo), and brain (MO59J and MO59K)), but their mechanism of action is drastically different. While FCP23 induces oxidative stress, DNA damage, and necrosis, FCP26 induces apoptosis through caspase activation.

The shift in consumer landscape towards vegan, vegetarian and flexitarian diets has created an unprecedented challenge in creating meat aroma from plant-based alternatives. The search for potential vegan solutions has thus led to a renewed interest in authentic meat flavour profiles. To gain a better understanding of the qualitative odour differences between boiled beef and boiled chicken, aroma extracts were isolated using Likens-Nickerson simultaneous distillation-extraction (SDE), selected expressly because the in-situ heating of the sample facilitates the capture of aroma intermediates during the cooking process, thereby mimicking the cooking of meat in stocks and stews. The extracts were then analysed by Gas Chromatography-Mass Spectrometry (GC-MS) and GC-Olfactometry (GC-O). Most of the volatiles identified in this study were sulfur-containing compounds, such as sulfides, thiols, mercaptoaldehydes and mercaptoketones, which are derived from the Maillard reaction. Meanwhile, lipid oxidation results in the formation of unsaturated aldehydes, such as alkenals and alkadienals. Families of thiazoles and 3-thiazolines were found in the extracts. Two novel 3-thiazolines (5-ethyl-2,4-dimethyl-3-thiazoline and 2-ethyl-4,5-dimethyl-3-thiazoline) which may also contribute to the meaty aroma were identified in this work and synthesised from their respective aldehyde and mercaptoketone precursors. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is an aggressive cancer insensitive to hormonal and human epidermal growth factor receptor 2 (HER2)-targeted therapies and has a poor prognosis. Therefore, there is a need for the development of convenient anticancer strategies for the management of TNBC. In this paper, we evaluate the antitumoral potential of a platinum(II) complex coordinated with the ligand 2-(3,5-diphenylpyrazol-1-yl)-2-thiazoline (DPhPzTn), hereafter PtDPhPzTn, against the TNBC cell line MDA-MB-231, and compared its effect with both cisplatin and its less lipophilic counterpart PtPzTn, the latter containing the ligand 2-(pyrazol-1-yl)-2-thiazoline (PzTn). Then, the putative potentiating actions of melatonin, a naturally occurring antioxidant with renowned antitumor properties, on the tumor-killing ability of PtDPhPzTn were also checked in TNBC cells. Our results show that PtDPhPzTn presented enhanced cytotoxicity compared to both the classical drug cisplatin and PtPzTn. In addition, PtDPhPzTn was able to induce apoptosis, being more selective for MDA-MB-231 cells when compared to non-tumor breast epithelial MCF10A cells. Likewise, PtDPhPzTn produced moderate S phase arrest and greatly impaired the migration ability of MDA-MB-231 cells. Most importantly, the co-stimulation of TNBC cells with PtDPhPzTn and melatonin substantially enhanced apoptosis and markedly improved the anti-migratory action compared to PtDPhPzTn alone. Altogether, our findings provide evidence that PtDPhPzTn and melatonin could be potentially applied to breast cancer treatment as powerful synergistic agents. [ABSTRACT FROM AUTHOR]

Chagas disease, a century-old disease that mainly affects the impoverished population in Latin America, causes high morbidity and mortality in endemic countries. The available drugs, benznidazole (Bz) and nifurtimox, have limited effectiveness and intense side effects. Drug repurposing, and the development of new chemical entities with potent activity against Trypanosoma cruzi, are a potential source of therapeutic options. The present study describes the biological activity of two new series of pyrazole-thiazoline derivatives, based on optimization of a hit system 5-aminopyrazole-imidazoline previously identified, using structure–activity relationship exploration, and computational and phenotype-based strategies. Promising candidates, 2c, 2e, and 2i derivatives, showed good oral bioavailability and ADMET properties, and low cytotoxicity (CC50 > 100 µM) besides potent activity against trypomastigotes (0.4–2.1 µM) compared to Bz (19.6 ± 2.3 µM). Among them, 2c also stands out, with greater potency against intracellular amastigotes (pIC50 = 5.85). The selected pyrazole-thiazoline derivatives showed good permeability and effectiveness in the 3D spheroids system, but did not sustain parasite clearance in a washout assay. The compounds' mechanism of action is still unknown, since the treatment neither increased reactive oxygen species, nor reduced cysteine protease activity. This new scaffold will be targeted to optimize in order to enhance its biological activity to identify new drug candidates for Chagas disease therapy. [ABSTRACT FROM AUTHOR]

A simple tert‐butyl hydroperoxide (TBHP)‐mediated method has been developed to construct selenated oxazolines/thiazolines under microwave irradiation. The selenocyclization of N‐allylbenzamides/benzthioamides could be achieved owing to the addition of an active electrophilic selenium species, generated in situ from diphenyl diselenide on reacting with TBHP, at their olefinic site. The reaction mechanism was confirmed by intercepting and characterizing all the proposed intermediates by ESI‐QTOF‐MS and NMR study. This method offers several advantages including simpler reaction conditions, shorter reaction time, catalyst‐free, thus rendering a competent alternative to the synthesis of selenated oxazolines/thiazolines in yields of upto 95 %. [ABSTRACT FROM AUTHOR]

[Display omitted] • A novel fluorescent probe (QT2) demonstrates highly selective quenching with Cu2+. • QT2 instantaneously responds to Cu2+ with an extremely low LOD of 4.84 ppb in aqueous media. • The 1:1 complex of QT2 ·Cu2+ is characterized by SC-XRD. • QT2 is applied via a paper-based strip for Cu2+ detection by the naked eye at 25 ng. • QT2 is utilized to quantitatively determine the amount of Cu2+ in water and food samples. Two novel fluorescent probes for Cu2+ detection have been developed based on thiazoline-quinoline conjugates bearing a 4-ethynyl-N,N-dimethylaniline unit (QT1 and QT2). QT2 exhibits instantaneous fluorescence quenching of Cu2+ with an emissive change from bright orange to arctic blue under UV light irradiation (365 nm). The plots of I 0 /I against Cu2+ concentrations show a good linear relationship that ranges from 0 to 50 µM with a coefficient of determination (R2) = 0.9906 and a limit of detection (LOD) of 76 nM, which is considered low (4.84 ppb). A 1:1 complexation between QT2 and Cu2+ was confirmed by UV–Vis titration, ESI-MS, and SC-XRD. The QT2 ·Cu2+ complex was dissociated by the addition of EDTA. The fluorescence quenching mechanism involves the ligand-to-metal charge transfer (LMCT) of a paramagnetic Cu2+ complex. The QT2 probe on a paper-based strip was used to determine the amount of Cu2+ in water and food samples (shiitake mushrooms and oysters). [ABSTRACT FROM AUTHOR]

Synthesis, reactivity, characterization, and catalytic activities of a series of palladium(II) complexes containing the thiazolinyl‐picolinamide derived pincer ligand is reported. Treatment of 2‐aminobenzonitrile with cysteamine and subsequent treatment with 2‐picolinic acid afforded the thiazolinyl‐picolinamide derived tridentate pincer ligand N∩N∩N (2). Treatment of 2 either with (COD)PdCl2 or PdCl2 in 1 : 1 ratio afforded the palladium(II) complex [(κ3‐N∩N∩N)PdCl] (3). A reaction between Pd(OAc)2 and 2 in equimolar ratio in dichloromethane gave [(κ3‐N∩N∩N)Pd(η1‐OAc)] (4) which on further treatment with triflic acid in acetonitrile produced the [(κ3‐N∩N∩N)Pd(N≡C−CH3)]OTf (5). The complex 5 was further treated with auxiliary ligands to produce the cationic heteroleptic palladium complexes, [(κ3‐N∩N∩N)Pd(NC5H5)]OTf (6), [(κ3‐N∩N∩N)Pd(NC5H4CN)]OTf (7), and [(κ3‐N∩N∩N)Pd(NC5H4NMe2)]OTf (8), respectively. The newly synthesized compounds were characterized by 1H and 13C{1H} NMR spectroscopic techniques and the molecular structures of 2–4, 6 and 8 were established. The catalytic activity of palladium(II) complexes (3–8) were evaluated for the acylative Suzuki coupling reaction between aryl carboxylic acids and arylboronic acids to yield unsymmetrically substituted biaryl ketones. The effect of reaction conditions viz., solvent, base, temperature, catalyst loading were evaluated, and complex 4 was found to be an excellent catalyst with a maximum TOF of 19.8 min−1. [ABSTRACT FROM AUTHOR]

The emergence of antibiotic resistance among microbial pathogens is a serious public health problem, resulting in a constant need of discovering new antibiotics. For this purpose, we synthetized and determined the antimicrobial activity of copper (Cu), cobalt (Co), and tin (Sn) complexes coordinated with scorpionate ligand in a tridentate mode against microorganisms of clinical importance. New complexes with the sodium hydrotris(2-mercaptothiazolyl)borate ligand were characterized by physicochemical and spectroscopic techniques (UV-vis, IR, 1H and 13C NMR). Moreover, their antimicrobial activity was evaluated using microdilution broth method. Cytotoxicity was determined in Vero cells and the selectivity index (SI) was calculated. The coordination with metals increased the ligand antimicrobial activity, which showed no activity when evaluated alone (MIC>1,080 µM). Cu-complex (1) had activity against Candida albicans and C. krusei, with MICs of 130 and 66 µM, respectively. The compounds had low toxicity on Vero cells and chemo-informatics assays corroborated a low systemic toxic effect. The SI revealed that the compound 1 was 16 times more selective for C. krusei and 8 times more selective for C. albicans in relation to Vero cells. The Cu-complex stands out as a potential prototype for the development of new antifungal agents.

Triple-negative breast cancer (TNBC) is an aggressive cancer insensitive to hormonal and human epidermal growth factor receptor 2 (HER2)-targeted therapies and has a poor prognosis. Therefore, there is a need for the development of convenient anticancer strategies for the management of TNBC. In this paper, we evaluate the antitumoral potential of a platinum(II) complex coordinated with the ligand 2-(3,5-diphenylpyrazol-1-yl)-2-thiazoline (DPhPzTn), hereafter PtDPhPzTn, against the TNBC cell line MDA-MB-231, and compared its effect with both cisplatin and its less lipophilic counterpart PtPzTn, the latter containing the ligand 2-(pyrazol-1-yl)-2-thiazoline (PzTn). Then, the putative potentiating actions of melatonin, a naturally occurring antioxidant with renowned antitumor properties, on the tumor-killing ability of PtDPhPzTn were also checked in TNBC cells. Our results show that PtDPhPzTn presented enhanced cytotoxicity compared to both the classical drug cisplatin and PtPzTn. In addition, PtDPhPzTn was able to induce apoptosis, being more selective for MDA-MB-231 cells when compared to non-tumor breast epithelial MCF10A cells. Likewise, PtDPhPzTn produced moderate S phase arrest and greatly impaired the migration ability of MDA-MB-231 cells. Most importantly, the co-stimulation of TNBC cells with PtDPhPzTn and melatonin substantially enhanced apoptosis and markedly improved the anti-migratory action compared to PtDPhPzTn alone. Altogether, our findings provide evidence that PtDPhPzTn and melatonin could be potentially applied to breast cancer treatment as powerful synergistic agents.

The shift in consumer landscape towards vegan, vegetarian and flexitarian diets has created an unprecedented challenge in creating meat aroma from plant-based alternatives. The search for potential vegan solutions has thus led to a renewed interest in authentic meat flavour profiles. To gain a better understanding of the qualitative odour differences between boiled beef and boiled chicken, aroma extracts were isolated using Likens-Nickerson simultaneous distillation-extraction (SDE), selected expressly because the in-situ heating of the sample facilitates the capture of aroma intermediates during the cooking process, thereby mimicking the cooking of meat in stocks and stews. The extracts were then analysed by Gas Chromatography-Mass Spectrometry (GC-MS) and GC-Olfactometry (GC-O). Most of the volatiles identified in this study were sulfur-containing compounds, such as sulfides, thiols, mercaptoaldehydes and mercaptoketones, which are derived from the Maillard reaction. Meanwhile, lipid oxidation results in the formation of unsaturated aldehydes, such as alkenals and alkadienals. Families of thiazoles and 3-thiazolines were found in the extracts. Two novel 3-thiazolines (5-ethyl-2,4-dimethyl-3-thiazoline and 2-ethyl-4,5-dimethyl-3-thiazoline) which may also contribute to the meaty aroma were identified in this work and synthesised from their respective aldehyde and mercaptoketone precursors.

Crystal structures of two Pt(II) complexes with square-planar geometry were determined. Cytotoxic activity of the compounds was studied towards HeLa, HL-60 and U-937 tumor cell lines. Cytotoxicity was only shown in non-solid tumor cell lines, the lowest IC 50 being produced by PtDMPzTn in U-937 cells. [Display omitted] Cisplatin is one of the most used chemotherapeutic agents nowadays. However, it presents several and severe side effects. For that, the synthesis of new analogues of cisplatin is crucial to improve the current therapies. In this work, two squared-planar Pt(II) analogues of cisplatin were presented. These analogues included a bidentate ligand molecule with a 3,5-dimethyl-pyrazole ring and a thiazine (DMPzTz) or thiazoline (DMPzTn) ring. The chemical characterization covered single-crystal X-ray diffraction, infrared spectroscopy (IR) and elemental analysis. Their potential anticarcinogenic ability was studied in three different human tumor cell lines, i.e., histiocytic lymphoma (U-937), promyelocytic leukemia (HL-60) and epithelial cervix carcinoma (HeLa) via cytotoxicity assay. The results showed moderate cytotoxic effect of the complexes on leukemic cell lines, with scarce effect on solid tumor cell line HeLa. Lower IC 50 values were found for U-937 cell line, being 32.3 ± 1.2 µmol/dm3 for PtDMPzTn and 43.0 ± 1.4 µmol/dm3 for PtDMPzTz. The comparison with previously synthesized analogues with phenyl substitutions or no substitutions in the pyrazole ring, allows to conclude that the presence of ligands with methyl substituted-pyrazole ring did not improve the effect of the complexes. In addition, the main effect of these potential chemotherapeutic agents is produced by the presence of platinum(II) as metal center, since the free ligands do not show any significant activity. [ABSTRACT FROM AUTHOR]

Chagas disease, a century-old disease that mainly affects the impoverished population in Latin America, causes high morbidity and mortality in endemic countries. The available drugs, benznidazole (Bz) and nifurtimox, have limited effectiveness and intense side effects. Drug repurposing, and the development of new chemical entities with potent activity against Trypanosoma cruzi, are a potential source of therapeutic options. The present study describes the biological activity of two new series of pyrazole-thiazoline derivatives, based on optimization of a hit system 5-aminopyrazole-imidazoline previously identified, using structure–activity relationship exploration, and computational and phenotype-based strategies. Promising candidates, 2c, 2e, and 2i derivatives, showed good oral bioavailability and ADMET properties, and low cytotoxicity (CC50 > 100 µM) besides potent activity against trypomastigotes (0.4–2.1 µM) compared to Bz (19.6 ± 2.3 µM). Among them, 2c also stands out, with greater potency against intracellular amastigotes (pIC50 = 5.85). The selected pyrazole-thiazoline derivatives showed good permeability and effectiveness in the 3D spheroids system, but did not sustain parasite clearance in a washout assay. The compounds’ mechanism of action is still unknown, since the treatment neither increased reactive oxygen species, nor reduced cysteine protease activity. This new scaffold will be targeted to optimize in order to enhance its biological activity to identify new drug candidates for Chagas disease therapy.

An efficient protocol for the synthesis of thiazoline derivatives via electrophilic cyclization of N‐allyl thiourea derivatives with the low‐cost and readily available cupric halides has been developed. The notable features of this reaction are the formation of new C‐X and C‐S bonds, mild reaction conditions, short reaction time and the excellent yields. The present method was also employed for the preparation of corresponding oxazoline derivatives in very good yields. [ABSTRACT FROM AUTHOR]

Thiazoline functionalized periodic mesoporous organosilica (TPMO) supported palladium nanoparticles (Pd‐TPMO) were fabricated through a co‐condensation approach and successive incorporation of palladium nanoparticles using a double‐solvent technique. The TPMO and Pd‐TPMO were characterized through 29Si MAS NMR, FTIR, SAXS, XPS, FESEM, TEM and N2 adsorption‐desorption, which revealed the morphological and physicochemical properties of the materials. The catalytic performance of Pd‐TPMO was evaluated for hydrogenation of industrially important compounds and Csp2−Csp2 bond‐formation reactions. The Pd‐TPMO mediated catalytic reactions were found to be effective in producing the corresponding products with excellent yields and selectivity. The size and stability of palladium nanoparticles within the confined organosilica framework promotes excellent activity and recyclability of the catalyst without a significant loss in the yields for hydrogenation and Csp2−Csp2 bond‐formation reactions. [ABSTRACT FROM AUTHOR]

This research includes the synthesis of new heterocyclic containing 1,2,4-triazole, oxazoline and thiazoline derivatives of 2,5 dimarcaptothiadiazole. The preparation process started by the reaction of 2,5 dimercapto 1,3,4 thiadiazole (1) with ethyl chloroacetate to give diethyl 2,2'-(1,3,4-thiadiazole-2,5-diyl)bis(sulfanediyl)diacetate (2). Compound (2) reacted with hydrazine hydrate to give 2,5 bis(mercapto acetichydrazide) 1,3,4 thiadiazole(3). Compound (2) reacted with thiosemicarbazide to give 2,2'-(2,2'-((1,3,4-thiadiazole-2,5-diyl)bis(sulfanediyl))bis(acetyl))bis(hydrazine-1- carbothioamide) (2a). Compound (3) reacted with (phenylisocynate or phenylisothiocynate) to give 2,2'-(2,2'-((1,3,4- thiadiazole-2,5-diyl)bis(sulfanediyl))bis(N-phenylhydrazine-1-carboxamide) and 2,2'-(2,2'-((1,3,4-thiadiazole-2,5- diyl)bis(sulfanediyl))bis(N-phenylhydrazine-1-carbothioamide) (4-5). Compounds (2a,4,5) reacted with 4N sodium hydroxide solution to give 1,2,4-triazole (2b,4a,5a). Compounds (4 or 5) reacted with (p-bromophenacyl bromide and p-phenylphenacyl bromide) to give oxazoline (6,7) and thiazoline (8,9) derivatives. [ABSTRACT FROM AUTHOR]

Novel findings during the course of the total synthesis of sulfur-containing natural products are described. These natural products include sporidesmin A, dehydrogliotoxin, tantazole B, and leinamycin. [ABSTRACT FROM AUTHOR]

Abstract A thiazoline and pyrene containing sensor 1 was synthesized via one-pot reaction and utilized as a highly selective and sensitive fluorescence "turn-on" sensor for Cu2+ detection, via the fluorescence enhancement of pyrene monomer emission. The 2:1 stoichiometry of 1 and Cu2+ was calculated from Job's plots based on fluorescent titrations, and the complexation of 1 with Cu2+ was also supported by mass spectra, Fourier transform infrared spectra, proton NMR spectra and density functional theory analysis. The fluorescence intensity of 1 at 389 nm and 410 nm increased significantly upon the addition of Cu2+. Limit of detection and association constant value of 1 –Cu2+ were calculated using standard deviations and linear fittings, respectively. Results showed that 1 was active for Cu2+ detection in the wide pH range of 2.0–11.0. Graphical abstract A thiazoline and pyrene containing sensor 1 was utilized as a highly selective and sensitive fluorescence "turn-on" sensor for Cu2+ detection via the fluorescence enhancement of pyrene monomer emission. Unlabelled Image Highlights • Thiazoline−pyrene based fluorescence sensor was synthesized via one-pot reaction. • The Cu2+ was detected via the fluorescence enhancement of pyrene monomer emission. • The detection limit of Cu2+ was ~0.11 μM which was lower than EPA and WHO standards. • The sensor showed wide pH applicability (pH 2.0–11.0), and wide detection range for Cu2+ (0–1.0 mM). [ABSTRACT FROM AUTHOR]

Abstract: A metal‐free oxidative difunctionalization of N‐allylamides and N‐allylthioamides has been developed. This system features the use of a hypervalent iodine oxidant with electron‐deficient amines to access 5‐amino‐oxazoline and thiazoline scaffolds under mild conditions. Notably, various electron‐deficient amines were systematically evaluated and we verified the reaction profile was originated from an attached (benzene)sulfonyl group. [ABSTRACT FROM AUTHOR]

Cell active inhibitors of glycoside processing enzymes are valuable research tools that help us understand the physiological roles of this diverse class of enzymes. endo- N-Acetylglucosaminidases have gained increased attention for their important roles in both mammals and human pathogens; however, metabolically stable cell active inhibitors of these enzymes are lacking. Here, we describe a divergent synthetic strategy involving elaboration of a thiazoline core scaffold. We illustrate the potential of this approach by using the copper catalysed azide-alkyne click (CuAAC) reaction, in combination with a suitable catalyst to avoid poisoning by the thiazoline moiety, to generate a targeted panel of candidate inhibitors of endo- N-acetylglucosaminidases and chitinases. [ABSTRACT FROM AUTHOR]

In this study, novel N'-(3-cyclohexyl/phenyl-4-(substituted phenyl)thiazole-2(3H)-ylidene)- 2-[(5,6,7,8-tetrahydronaphthalen-2-yl)oxy]acetohydrazide (4a-4k) derivatives were synthesized and their anticancer potency were evaluated on human breast adenocarcinoma cell line (MCF-7), human lung carcinoma cell line (A549) and mouse embryoblast cell line (NIH/3T3) using the MTT method, DNA synthesis inhibition and flow cytometric analysis. Compound 4e bearing 4-methoxyphenyl moiety exhibited the highest antitumor efficiency against MCF-7 cell line with higher DNA synthesis inhibition and apoptotic cell percentages (ealy+late apoptotic cell). On the other hand, compounds 4f, 4g, and 4h bearing 4-bromo, 4-chloro and 4-florophenyl moieties, respectively caused excellent apoptosis levels against A549 cell line when treated with lower concentration even than cisplatin. Anticholinesterase activity of the compounds were also tested, compound 4h showed 49.92% inhibition of acetylcholinesterase (AChE). [ABSTRACT FROM AUTHOR]

A series of new thiazoline derivatives were synthesized. Structure analyses were accomplished employing 1H-NMR, 13C-NMR, X-ray and MS techniques. The in vitro antitumor activities were assessed against human hepatocellular carcinoma (HepG-2) and colorectal carcinoma (HCT-116) cell lines. The results revealed that the thiazolines 5b and 2c exhibited significant activity against the two cell lines. The in vitro antimicrobial screening showed that the thiazolines 2c, 5b and 5d showed promising inhibition activity against Salmonella sp. Additionally, the inhibition activity of thiazolines 2e and 5b against Escherichia coli was comparable to that of the reference compound gentamycin.

New N3-benzylidene (substituted)-2-phenyl-N4-(thiazol-2-yl)-quinazoline-3,4-( 4H )-diamine derivatives were design and synthesized by a sequence of reactions starting from appropriate 6-methyl anthranilic acid. The title compounds were screened for in vitro dipeptidyl peptidase IV (DPP-4) inhibitory activity and diphenyl-2-picryl-hydrazyl (DPPH) assay and results showed significant to good activity in compared to Linagliptin for antidiabetic activity and Ascorbic acid for antioxidant activity. Compound 7g (IC 50 = 0.76 nM) exhibited most promising DPP-4 inhibitory activity and also showed good antioxid and result. Docking study was also performed to provide an insight about the binding mode into binding sites of DPP-4 enzyme. Hopefully in future, compound 7g could be used as a lead compound for developing new antidiabetic agent with good antioxidant property. [ABSTRACT FROM AUTHOR]

Zn was produced and separated for medical applications. Possibilities and perspectives for production of radiopharmaceuticals based on Zn containing derivatives of thiazine, thiazoline and thiourea are considered. Each one of the latters is a zinc chelator and a nitric oxide synthase (NOS) effector at the same time. Cytotoxic effect of NOS activator and NOS inhibitors are shown in experiments with HL-60, K-562 and MOLT-4 cell lines and in bone marrow cells of the acute B-lymphoblastic leukemia patients. Some of those compounds are worthy to get selected for further application as radiopharmaceuticals including their antitumor speciements. [ABSTRACT FROM AUTHOR]

A one-pot, three-component reaction has been developed and successfully employed for the synthesis of biologically relevant, highly functionalized spirooxindole-fused 3-thiazoline derivatives. Starting from ammonia, three mercapto carbonyl components and a series of substituted isatins, products were obtained in good yields (24 examples), by following a simple and rapid protocol. The obtained thiazolines proved to be optimal substrates for further transformations, including the three-component Ugi-Joullié reaction. [ABSTRACT FROM AUTHOR]

In this paper, synthesis of a novel Schiff base ligand based on bis(2-amino-4-pheny1-5-thiazolyl)disulfide and its corresponding Ni(II) complex was reported. This ligand was prepared through the formation of an imine bond between 2-hydroxy-1-naphthaldehyde and bis(2-amino-4-phenyl-5-thiazol)disulfide in absolute methanol as solvent. The characterizations were performed by FT-IR, H NMR, C NMR, elemental analysis, and single crystal X-ray analysis. In the molecular structure, the ligand possessed anti-conformation around -S-S- bond and monomeric moieties were linked into the chains through the C-H⋯O and π⋯ π interactions. The reaction of the synthesized ligand with NiCl in methanol afforded the corresponding Ni(II) complex. The resulting product was further investigated by thermal gravimetric and differential thermal analysis, which confirmed the formation of desired polymeric complex. The electrochemical behavior and formation of Ni(II) complex in dimethyl sulfoxide (DMSO) solution were investigated by means of cyclic voltammetry and UV-Vis titration, respectively. Graphical abstract: [ABSTRACT FROM AUTHOR]

Trichloroisocyanuric acid as a commercially available and inexpensive catalyst has been used in a new, facile and efficient procedure for the synthesis of 2-oxazolines, 2-imidazolines and 2-thiazolines through the reaction of nitriles with 2-aminoethanol, ethylenediamine or 2-aminoethanthiol under solvent -free conditions.