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Sulfated tungstate catalyzed an efficient and ecofriendly protocol has been described for the synthesis of 2-substituted benzothiazoles. The corresponding benzothiazoles were obtained using a condensation reaction of 2-aminothiophenol with various aldehydes under ultrasound irradiation at room temperature. Various functional groups on the 2-aminothiophenol as well as on the aldehydes were tolerated to provide 2-substituted benzothiazoles derivatives in excellent yields. The faster reaction rate, solvent-free or mild reaction conditions, wide functional group compatibility, excellent yields, easy work-up procedure, and excellent catalyst recyclability are the advantages of this protocol. These advantages make this process more practicable, cost-effective, and environmentally benign. [ABSTRACT FROM AUTHOR]

An environmentally friendly and efficient protocol for the synthesis of benzimidazoles by mortar–pestle grinding technique in the presence of acetic acid as a catalyst is reported. This mechanochemical method proceeded with the condensation of aldehyde and o-phenylenediamine followed by cyclization reaction, leading to the formation of the corresponding benzimidazoles in yields up to 97%. This protocol could also be applied for the synthesis of benzothiazoles and benzoxazoles. [ABSTRACT FROM AUTHOR]

Two novel groups of rod-like molecules with benzothiazole-aromatic systems: one group (group A) having an ester linkage with different thioalkyl chain length and the other (group B) ester- and azomethine-linkages with methoxy groups in the tip of the molecules were synthesised. The structures of the synthesised compounds were confirmed by using physicochemical techniques such as 1H NMR, mass spectra, FT-IR spectra, melting points, and elemental analyses. Differential scanning calorimeter and polarising optical microscopy have been employed to verify their liquid crystalline behaviours and transition temperatures. All the synthesised compounds (groups A and B) showed enantiotropic nematic phase except the compound 13d showed the nematic phase in cooling only. The mesomorphic properties of the present compounds were compared with some other structurally related compounds to understand the chemical structure–mesophase properties relationship. The thermal range of nematic phase for the compounds (group A) were decreased with the increase of the thioalkyl chain length. The liquid crystalline properties of the compounds (group B) were greatly affected by the position of terminal methoxy groups. The change of the position of terminal methoxy groups in the compounds (group B) was theoretically studied to investigate if the theoretical calculations possess an agreement with the practical results. [ABSTRACT FROM AUTHOR]

Inspired by the mechanism of the clock reaction, we rationally constructed a novel phosphomolybdenum blue (PMB) clock catalytic system for a highly efficient synthesis of benzimidazoles and benzothiazoles simply at ambient temperature. The current PMB clock catalytic system exhibits a sharp decoloration event to announce the depletion of the intermediateconstraint, making this synthetic approach self‐indicating and TLC‐free.31P NMR and XPS analysis of PMBcatalyst showed that only two Mo6+ atoms are reduced to Mo5+ atoms in the Keggin structure due to the moderate reducibility of benzimidazoline and benzothiazoline intermediates. Thus,the active Keggin‐type POM cluster could be well maintained in DMSO during the redox cycling of phosphomolybdic acid (PMA) and PMB. 1H NMR tracing experiment not only confirmed the proposed reaction mechanism but also showed that PMB exerts Lewis acid catalytic activityat the early phase of the reaction other than the expected redox catalytic activity. [ABSTRACT FROM AUTHOR]

Nitrogen containing heterocyclic compounds such as benzoxazole derivatives have been found to be pharmacologically active and are being employed as starting material for several drug discovery researches. Synthetic strategies invention to produce such beneficial moieties is on focus of synthetic organic chemists, as a result various efficient protocols have been developed since past decades to synthesize different medicinally useful benzoxazole derivatives. In this review, we attempt to organize recent synthetic strategies explored by chemists to produce benzoxazole derivatives by the reaction of 2-aminophenol with various reactants in different reaction conditions such as solvents, catalysts, temperature etc. Therefore, the updated synthetic information present in this review may be helpful to the researchers to develop better synthetic protocols for novel medicinally active derivatives.

Background : A high-fat diet (HFD) is generally associated with an increased risk of mental disorders that constitute a sizeable worldwide health. A HFD results in the gut microbiota-brain axis being altered and linked to mental disorders. Hypocretin-1, which can promote appetite, has been previously confirmed to be associated with depression. However, no exact relationship has been found for hypocretin between depression and HFDs. Methods : Adult male SD rats were randomly assigned to either a HFD or a normal diet for eight weeks, followed by behavioral tests and plasma biochemical analyses. Then, we investigated the protein and mRNA levels of inflammation-related factors in the hippocampus. We also observed morphological changes in brain microglia and lipid accumulation. Additionally, metagenomic and metabolomic analyses of gut microbiomes were performed. 3T3-L1 cells were utilized in vitro to investigate the impact of hypocretin receptor 1 antagonists (SB334867) on lipid accumulation. To consider the connection between the brain and adipose tissue, we used a conditioned medium (CM) treated with 3T3-L1 cells to observe the activation and phagocytosis of BV2 cells. Following a 12-week period of feeding a HFD to C57BL/6 mice, a three-week intervention period was initiated during which the administration of SB334867 was observed. This was followed by a series of assessments, including monitoring of body weight changes and emotional problems, as well as attention to plasma biochemical levels and microglial cell phenotypes in the brain. Results : The HFD rats displayed anxiety and depressive-like behaviors. HFD rats exhibited increased plasma HDL, LDL, and TC levels. A HFD also causes an increase in hypocretin-1 and hypocretin-2 in the hypothalamus. Metagenomics and metabolomics revealed that the HFD caused an increase in the relative abundance of associated inflammatory bacteria and decreased the abundance of anti-inflammatory and bile acid metabolites. Compared with the CTR group, hippocampal microglia in the HFD group were significantly activated and accompanied by lipid deposition. At the same time, protein and mRNA expression levels of inflammation-related factors were increased. We found that SB334867 could significantly reduce lipid accumulation in 3T3-L1 cells after differentiation. The expression of inflammatory factors decreased in the SB334867 group. The administration of SB334867 was found to reverse the adverse effects of the HFD on body weight, depressive-like behaviour and anxiety-like mood. Furthermore, this treatment was associated with improvements in plasma biochemical levels and a reduction in the number of microglia in the brain. Conclusions : In summary, our results demonstrated that a HFD induced anxiety and depressive-like behaviors, which may be linked to the increased hypocretin-1 level and lipid accumulation. Supplementation with SB334867 improved the above. These observations highlight the possibility of hypocretin-1 inducing the risk of HFD-associated emotional dysfunctions.

6-methoxybenzoxazolinone (6-MBOA) is a secondary plant metabolite predominantly found in monocotyledonous plants, especially Gramineae. In damaged tissue, 2-β-D-glucopyranosyloxy-4-hydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA-Glc) is hydrolyzed to DIMBOA, which spontaneously decomposes into 6-MBOA. It is commonly detected in plants consumed by voles and livestock and can also be present in cereal-based products. Discovered in 1955, this compound is renowned for its ability to trigger animal reproduction. However, there is a lack of research on its functional and mechanistic properties, leaving much of their potential unexplored. This review aimed to comprehensively summarize the effects of 6-MBOA on animal reproduction and human health, as well as its defensive role against herbivores. Studies have shown that 6-MBOA effectively inhibits the digestion, development, growth, and reproduction of insects. 6-MBOA may act as a partial agonist of melatonin and exert a regulatory role in mammalian reproduction, resulting in either promoting or inhibiting effects. 6-MBOA has been theorized to possess anti-tumor, anti-AIDS, anti-anxiety, and weight-loss effects in humans. However, insufficient attention has been paid to its defense properties against mammalian herbivores, and the mechanisms underlying its effects on mammalian reproduction remain unclear. In addition, research on its impact on human health is still in its preliminary stages. The review emphasizes the need for further systematic and comprehensive research on 6-MBOA to fully understand its diverse functions. Elucidating the effects of 6-MBOA on animal reproduction, adaptation, and human health would advance our understanding of plant-herbivore coevolution and the influence of environmental factors on animal population dynamics. Furthermore, this knowledge could potentially promote its application in human health and animal husbandry., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose of Review: Cardiac amyloidosis (CA) is a condition characterized by misfolding and extracellular deposition of proteins, leading to organ dysfunction. While numerous forms of CA exist, two subtypes dominate clinical prevalence: Transthyretin amyloid (ATTR) and immunoglobulin light chain amyloid., Recent Findings: The current scientific landscape reflects the urgency to advance therapeutic interventions with over 100 ongoing clinical trials. Heart failure treatment is affected by CA phenotype with poor tolerance of otherwise frequently used medications. Treating comorbidities including atrial fibrillation and valvular disease remains a challenge in CA, driven by technical difficulties and uncertain outcomes. Tafamidis is the first ATTR-stabilizer approved with a rapidly growing rate of clinical use. In parallel, various new therapeutic classes are in late-stage clinical trials including silencers, antibodies and genetic therapy. Managing CA is a critical challenge for future heart failure care. This review delineates the current standard-of-care and scientific landscape of CA therapy., (© 2024. The Author(s).)

Many interactions between small molecules and particles occur in solutions. They are surrounded by other molecules that do not react, for example, biological processes in water, chemical reactions in gas or liquid solutions, and environmental reactions in air and water. However, predicting the rate of such diffusive interactions remains challenging, due to the random motion of molecules in solutions, as exampled by the famous Brownian motion of pollen particles. In this report, we experimentally confirmed that a disruptive rate equation we have published before can predict the association rate of typical adsorption at interfaces, which has a surprising fraction order of 4/3 that has not been considered before. This could be an important step toward a generalized method to predict the adsorption rate of many reactions.

Background and Aims: The PROMINENT trial, a cardiovascular outcome trial of the triglyceride- and remnant cholesterol-lowering agent pemafibrate, has shown neutral results despite reduction in plasma triglycerides and remnant cholesterol. We tested the hypothesis that absolute mass changes in remnant cholesterol, LDL cholesterol, and apolipoprotein B explain the results of the PROMINENT trial., Methods: Among 108,431 individuals from the Copenhagen General Population Study (CGPS), those who met the key inclusion criteria of the PROMINENT trial were analyzed to mimic the trial design. Endpoint atherosclerotic cardiovascular disease (ASCVD) was cardiovascular death, myocardial infarction, ischemic stroke, and coronary revascularization as defined in PROMINENT., Results: In the PROMINENT trial, treatment with pemafibrate resulted in -7 mg/dL (-0.18 mmol/L; -18 %) change in remnant cholesterol, +10 mg/dL (+0.26 mmol/L; +12 %) LDL cholesterol, and +5 mg/dL (+0.05 g/L; +5 %) apolipoprotein B. In the CGPS mimicking PROMINENT, the estimated hazard ratios for ASCVD were 0.97 (95 % confidence interval: 0.94-0.99) for a -7 mg/dL (-0.18 mmol/L) change in remnant cholesterol, 1.04 (1.01-1.07) for a +10 mg/dL (+0.26 mmol/L) change in LDL cholesterol, and 1.02 (1.01-1.03) for a +5 mg/dL (+0.05 g/L) change in apolipoprotein B. When combining absolute changes in remnant cholesterol, LDL cholesterol, and apolipoprotein B, the estimated hazard ratio for ASCVD was 1.05 (0.96-1.14) in the CGPS mimicking PROMINENT compared to 1.03 (0.91-1.15) in the PROMINENT trial., Conclusions: Absolute mass changes in remnant cholesterol, LDL cholesterol, and apolipoprotein B can explain results of the PROMINENT trial. The 3 mg/dL (0.08 mmol/L) higher total atherogenic cholesterol together with 5 mg/dL (0.05 g/L) higher apolipoprotein B seem to explain the trend toward more ASCVD in the pemafibrate arm., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: BGN reports consultancies or talks sponsored by AstraZeneca, Sanofi, Regeneron, Akcea, Amgen, Amarin, Kowa, Denka, Novartis, Novo Nordisk, Esperion, Silence Therapeutics, Abbott, Mankind, Lilly, and Arrowhead. TD reports a consultancy by Novo Nordisk. AL reports a talk sponsored by Amarin and a consultancy by Novartis., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

[Display omitted] New Niii complexes based on the substituted 2-(2-hydroxy-phenyl)benzoxazole have been synthesized from the corresponding ligands and nickel acetate. The crystal structure of bis[2-(1,3-benzoxazol-2-yl-κ N)-4,5-dichloro-3-(methoxycarbonyl)phenolate-κ O ]nickel(ii) has been determined by X-ray diffraction. The new Niii complexes have been screened for their antibacterial, protistocidal and fungistatic activities [ABSTRACT FROM AUTHOR]

A novel and efficient four‐component reaction in water is reported, enabling the efficient synthesis of benzoxazoles from aldehydes, benzo‐1,2‐quinones, hydroxylamine hydrochloride, and water via a C−H amination strategy. Importantly, water is not only employed as the solvent but also used as the oxygen source of the benzoxazole skeletons, while inorganic hydroxylamine hydrochloride serves as the nitrogen source. Preliminary mechanistic studies prove that the aldoxime rather than the quinone oxime is the reaction intermediate. [ABSTRACT FROM AUTHOR]

Versatile applications and unique performance of 1,1'‐bis(diphenylphosphanyl)ferrocene (dppf) in coordination chemistry and catalysis prompted the search for its analogs. This contribution describes the synthesis of the first donor‐unsymmetric dppf congeners bearing bulky and rigid 1,3,5,7‐tetramethyl‐2,4,6‐trioxa‐8‐phosphaadamantyl (CgP) donor groups, viz. Ph2PfcPCg (1) and Ph2PfcCH2PCg (2; fc=ferrocene‐1,1'‐diyl). Bis‐phosphanes 1 and 2 were converted into air‐stable Pd(0) complexes, [Pd(ma)(L^L)] (L^L=1 and 2; ma=maleic anhydride). Together with [Pd(ma)(dppf)], these complexes were applied as catalysts in Pd‐catalyzed C−H arylation of benzoxazoles with aryl chlorides in n‐butanol as an environmentally benign solvent. Among all catalysts tested in this study, complex [Pd(ma)(2)] performed the best, providing a high‐yield and selective synthesis of 2‐arylbenzoxazoles from a range of the generally less reactive chloroarenes at low catalyst loading (typically 1 mol.%). Under similar conditions, the structurally related heterocycles (e. g. 1‐methylbenzimidazole and benzothiazole) did not react. [ABSTRACT FROM AUTHOR]

4-((4-((Benzo[d]oxazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)methyl)-2H-chromen-2-ones 7k–z were synthesized by conventional as well as microwave irradiation method in order to obtain antimicrobial agents. The present green synthetic protocol explores facile work up procedure with excellent yields (82–92%) and purity. Docking studies exhibited strong binding interactions with enzyme N-myristoyl transferase (PDB ID: 4CAW) with excellent C-score values. Compounds 7k–z were screened for their in vitro antimicrobial activities. The compounds 7w and 7 y exhibited excellent antimicrobial results for all the tested microorganisms at MICs ranging from 3.12 to 6.25 µg/ml in comparison with the marketed drugs. [ABSTRACT FROM AUTHOR]

The properties of high stability, periodic porosity, and tunable nature of ordered mesoporous polymers make these materials ideal catalytic nanoreactors. However, their application in organocatalysis has been rarely explored. We report herein for the first time the incorporation of a versatile organocatalyst, 2,2,6,6‐tetramethyl‐1‐piperidinyloxy (TEMPO), into the pores of an FDU‐type mesoporous polymer via a pore surface engineering strategy. The resulting FDU‐15‐TEMPO possesses a highly ordered mesoporous organic framework and enhanced stability, and shows excellent catalytic activity in the selective oxidation of alcohols and aerobic oxidative synthesis of 2‐substituted benzoxazoles, benzimidazoles and benzothiazoles. Moreover, the catalyst can be easily recovered and reused for up to 7 consecutive cycles. [ABSTRACT FROM AUTHOR]

In this research work, we present a synthesis of silver and cobalt bimetal nanoparticles stabilized by a carboxymethyl cellulose biopolymer (CMC-AgCo) and its coating on a cellulose filter paper (CFP) to prepare the dip-catalyst. All the prepared samples were subjected to characterization by scanning electron microscopy for surface morphology, EDX, XRD and thermogravimetric analysis. The catalytic properties of the CFP/CMC-AgCo as dip-catalysts were evaluated in the reduction of organic nitroaromatic pollutants of 2,6-dinitrophenol to 2,6-diaminophenol as well as the 4-nitrophenol to 4-aminophenol. It was found that the reduction reaction advanced with the pseudo-first-order kinetics. The CFP/CMC-AgCo catalyzed the 2,6-diaminophenol and 4-nitrophenol with a reaction rate constant of 0.1244 and 0.177 min− 1, respectively. The separation of the CFP/CMC-AgCo was easy as it required a simple pulling of the strip from the reaction medium. Importantly, the catalytic reaction rates and conversion percentages of the two nitroaromatics were well-maintained for multiple times during recycling experiments. [ABSTRACT FROM AUTHOR]

Aim. Synthesis and characterization of styrylcyanine dye as a potential fluorescent probe for the detection in vitro of pathological amyloid fibrils and functional amyloid in S. aureus biofilm. Methods. Chemical synthesis, fluorescence spectroscopy, irradiation with a visible light source, confocal laser scanning microscopy, fluorescence microscopy. Results. Styrylcyanine dye is low fluorescent when free, but in the presence of amyloid fibrils in vitro shows an increase in the emission intensity up to 214 times depending on the amyloidogenic protein structure; the most pronounced enhancement was observed for fibrils of beta-lactoglobulin. Photostability of the dye in the free state is low, but binding to amyloid fibrils results in a strong increase of dye photostability. Upon staining S. aureus biofilm, the dye stains extracellular components of the biofilm matrix and does not penetrate the cell. Conclusion. This dye is suggested to visualize the functional amyloids of S. aureus biofilm with a red emission. [ABSTRACT FROM AUTHOR]

In the present study, a set of different benzoxazole derivatives has been synthesized from ethyl acetoacetate, ethoxymethylene malononitrile, NaNO2, and organic acids. Analytical instruments like proton NMR (¹H), carbon NMR (13C), infrared spectroscopy (IR), and LC-MS mass spectrometry were used for structural characterization. Synthesized molecules were evaluated for In-vitro antioxidant property (DPPH assay, Total antioxidant & reducing power method) and anti-diabetic property (alphaamylase & alpha-glucosidase assay). In silico, studies against Human pancreatic alpha-amylase (PDB ID: 3BAW) have been carried out to get the binding approach of the ligand towards the protein. The results demonstrated that compounds namely 5b, 6b, 3b and 4b had potent antioxidant and anti-diabetic activity compared with ascorbic acid and acarbose. [ABSTRACT FROM AUTHOR]

Background. Azomethines are known to be important intermediates for the preparation of benzoxazoles, which are biologically active compounds. Therefore, the development of methods for the synthesis of substituted azomethines is topical. Purpose: carrying out reactions of (substituted) aminophenols with aromatic aldehydes under various conditions and determining the factors affecting the type of products, determining their structures. Methodology. The reactions of 2-aminophenol, 4-nitro-2-aminophenol, 4-chloro-2-aminophenols with aldehydes were carried out under various conditions. As a result, azomethine and acetamide were obtained in high yields instead of the expected 2-arylbenzoxazoles. The structure of the synthesized substances was proved on the basis of the results of 1Hba 13C NMR spectroscopy and X-ray diffraction analysis. Originality: The synthesis of azomethines, components of the synthesis of heterocyclic compounds, was carried out. It was found that the condensation of aminophenols and aromatic aldehydes can proceed in different directions. Findings. Azomethine amides have been synthesized in high yields and are widely used for the synthesis of substituted benzoxazoles. The 1H and 13C NMR spectra of the obtained substances were analyzed, as well as the X-ray diffraction data of single crystals, and their chemical structures were established. [ABSTRACT FROM AUTHOR]

An efficient environmentally benign method for the synthesis of 1,2-disubstituted benzimidazole derivatives via one-pot multicomponent has been reported using aqueous extract of Acacia concinna pods as a naturally occurring surfactant type catalyst. The present surfactant medium was found superior and additive free for the condensation of o-phenylene diamine and two equivalent of aldehyde to yield 1,2-disubstituted benzimidazole derivatives in excellent yields under mild conditions. A simple, economically viable and biocompatible catalytic system suggested the possible utility of the present protocol for the large scale construction of benzimidazole derivatives. [ABSTRACT FROM AUTHOR]

New benzoxazole-terminated mesogenic compounds containing tolane moiety with high birefringence and large dielectric anisotropy, namely, 2-[4-[2-[4-alkoxyphenyl]ethynyl]-2,6-difluoro-phenyl]-benzoxazole derivatives (nPEDFPBx), were synthesised and investigated. Among them, the ones bearing methyl and nitro substituents at 5-position of benzoxazole moiety exhibit stable mesophase ranges of 30–71°C and 55–81°C during heating and cooling processes, respectively, while the non-substituted compounds exhibit no mesophase except the ones with long terminal alkoxy chain (n = 10, 12). Birefringence of nPEDFPBx is obtained from DFT theoretical calculation (0.446–0.583) and experimental measurement (0.395–0.499), respectively, where high birefringence is ascribed to their large π-conjugated molecule composed of benzene ring, acetylene linkage and benzoxazole moiety. Meanwhile, it is found that nPEDFPBx displays large dielectric anisotropy because of their high dipole moment. As an example, the compound 5PEDFPBM is doped into the liquid crystalline mixture as an additive, the properties of the resulting mixture, such as birefringence, dielectric anisotropy, clearing point and response time, are improved obviously, indicating high potential application for liquid crystalline mixture. [ABSTRACT FROM AUTHOR]

A metal‐free methodology for the synthesis of 1,2‐disubstituted and 2‐substituted benzimidazoles with high to excellent yields has been developed. The course of synthesis involves easy work‐up, straightforward purification, inexpensive reaction setup, and wide substrate scope under extremely mild and operationally simple conditions which makes the synthetic strategy more lucrative, practical and reliable. The serious challenge to carry out these reactions in a pure aqueous medium has been achieved at 75 °C in presence of air bubbles. The applicability of this operationally simple and metal‐free synthetic approach for the gram‐scale synthesis of benzimidazole derivatives with good yield (∼74%) further strengthens its potentiality for the synthesis at an industrial scale. [ABSTRACT FROM AUTHOR]

An elemental sulfur promoted strategy for the synthesis of a series of diverse 4H‐pyrimido[2,1‐b]benzothiazoles has been developed under metal and solvent‐free conditions. This methodology allows the facile and convenient synthesis of desired products in good to excellent yields. This process achieved broad substrate scope, inexpensive catalyst and mild reaction conditions. [ABSTRACT FROM AUTHOR]

Strongly luminescent tricarbonylrhenium(I) complexes are promising candidates in the field of optical materials. In this study, three new complexes bearing a 3-(2-pyridyl)-1,2,4-triazole (pyta) bidentate ligand with an appended phenyl group were obtained in very good yields owing to an optimized synthetic procedure. The first member of this series, i.e. complex 1, was compared with the previously studied complex RePBO to understand the influence of the fluorescent benzoxazole unit grafted on the phenyl ring. Then, to gauge the effect of steric hindrance on the luminescence properties, the phenyl group of complex 1 was substituted in the para position by a bulky tert-butyl group or an adamantyl moiety, affording complexes 2 and 3, respectively. The results of theoretical calculations indicated that these complexes were quite similar from an electronic point of view, as evidenced by the electrochemical study. In dichloromethane solution, under excitation in the UV range, all the complexes emitted weak phosphorescence in the red region. In the solid state, they could be excited in the blue region of the visible spectrum and they emitted strong yellow light. The photoluminescence quantum yield was markedly increased with raising the size of the substituent, passing from 0.42 for 1 to 0.59 for 3. The latter complex also exhibited clear waveguiding properties, unprecedented for rhenium complexes. From this point of view, these easy-synthesized and spectroscopically attractive complexes constitute a new generation of emitters for use in imaging applications and functional materials. However, the comparison with RePBO showed that the presence of the benzoxazole group leads to unsurpassed mechanoresponsive luminescence (MRL) properties, due to the involvement of a unique photophysical mechanism that takes place only in this type of complex. [ABSTRACT FROM AUTHOR]

The o‐hydroxyphenyl ethyl ketone skeleton is prevalent in many biologically active natural products and active pharmaceutical ingredients. Herein, a two‐step protocol has been developed for synthesis of various β‐substituted o‐hydroxyphenyl ethyl ketones. A base‐mediated ring opening of 4‐chromanone was used to introduce the β‐ethoxyl o‐hydroxyphenyl ethyl ketone intermediary, followed by nucleophile substitution under BF3 ⋅ Et2O assisted conditions to give the desired β‐carbon, nitrogen, or thiol substituted o‐hydroxyphenyl ethyl ketones. With the aid of this protocol, a silica‐supported cobalt(II) salen complex was successfully prepared and its structure was confirmed by FTIR, 13C MAS NMR, UV‐Vis absorption, and XPS spectra. The immobilized cobalt(II) salen catalyst not only displayed comparable catalytic activity in the synthesis of several heterocycles including 1,3‐oxazolidine, benzimidazole, and benzoxazole as compared with their homogeneous counterparts, but also could be recycled for several times without obvious loss of its catalytic activity. [ABSTRACT FROM AUTHOR]

Three new heteroleptic [Cu(NN)P2]+ type cuprous complexes 1–3 were designed and synthesized by utilizing a diimine ligand 5‐methyl‐2‐(2′‐pyridyl)‐benzoxazole (MePBO) and different phosphine ligands PPh3 (1), m‐Tol3P (2) and POP (3), (PPh3=triphenylphosphine, m‐Tol3P=tris(3‐methylphenyl)phosphine, POP=bis[2‐(diphenylphosphino)phenyl]ether), respectively. All complexes were characterized by single‐crystal X‐ray diffraction, spectroscopic analysis (IR, UV‐Vis), elemental analysis, and photoluminescence study. Single‐crystal X‐ray diffraction revealed that complexes 1–3 all adopt discrete cation complex structure with a tetrahedral CuN2P2 coordination geometry with diverse P−Cu−P angles. Their UV‐Vis absorption spectra exhibit a blue‐shift sequence under the enlarging of P−Cu−P angle from 3 to 2 then to 1. The PL emission peak wavelengths of 1–3 also present similar blue‐shift sequence (3→1/2). Their microsecond PL lifetime indicates that their PL behavior belongs to phosphorescence. TD‐DFT calculation and wavefunction analysis illuminate that the S1 and T1 states of 1–3 should all be assigned as (ML+L′L)CT states. Their UV‐Vis absorption and phosphorescence should be attributed to the charge transfer from the P−Cu−P segment to the MePBO ligand. Therefore, as P−Cu−P angle increases (lower HOMO), the energy of S1 and T1 states also increase, following the change of PL color. Additionally, the steric hindrance from substituents of phosphine ligand, as well as extra strong intra‐molecular π−π stacking interactions should effectively inhibit nonradiative decay so that an abnormal PL emission blue‐shift is observed from 1 to 2. [ABSTRACT FROM AUTHOR]

This paper reports the transition metal‐free C(sp3)−H sulfenylation of arylacetamides by using thiophenols as the sulfenyl reagents. The reactions take place in the presence of only K3PO4. Control experiments indicate that the reactions proceed via a featured sulfur‐centred free radical intermediate. In addition, the synthesis of 2‐thiomethyl benzoxazoles has been realized via the p‐toluenesulfonic acid (p‐TSA) promoted annulation of the sulfenylated products. [ABSTRACT FROM AUTHOR]

Recently, heterocyclic compounds play important role in drug industries. The benzothiazole (BTA) is a bicyclic compound in heterocyclic because of their biological properties. In this paper the synthesis and characterization of benzothiazole were reported. The chemical structures of synthesized compounds were established based on spectral data of ¹HNMR, 13CNMR, and IR. The mass of the novel compounds was established with the help of the LCMS test. The formation of the crystal was confirmed by powder XRD and the sharp peaks show the purity and crystalline nature of the samples. The photoluminescence spectra explain the optical property of the compound. The biological studies of synthesized compounds show that compound 5c possesses good antibacterial activity and compound 5d has good antifungal activity. [ABSTRACT FROM AUTHOR]

Twenty‐three benzoxazole derivatives were prepared through two‐step reaction strategy. The precursor, 2‐mercapto benzoxazole was synthesized by reacting 2‐amino phenol with carbon disulfide in the presence of potassium hydroxide. Then, 2‐mercapto benzoxazole was further reacted with substituted phenacyl/benzyl bromide to afford a range of substituted 2‐mercapto benzoxazole analogs. All compounds were characterized by different spectroscopic techniques including mass spectrometry and nuclear magnetic resonance spectroscopy, and investigated against urease enzyme. All analogs revealed good to moderate urease inhibition, ranging from IC50 = 17.50±0.10 to 42.50±0.44 μM. Few derivatives showed superior activity than thiourea (IC50=21.50±0.47 μM), standard inhibitor of urease enzyme. Structure‐activity relationship (SAR) revealed the crucial participation of various structural features in the inhibitory process. Compounds bearing methoxy and halogen substituents were found to show more potency as compared with other molecules. Molecular docking showed various interesting interactions established by molecules (ligand) with the active pocket of urease enzyme. [ABSTRACT FROM AUTHOR]

A simple and efficient TEMPO-mediated system for aerobic oxidative synthesis of 2-aryl benzoxazoles from readily available benzoxazoles and primary benzylic and hetero benzylic amines is presented in one pot. The reaction proceeds through the ring-opening of benzoxazoles and is followed by oxidative condensation with benzylamines. These metal-free, straightforward reactions worked well with a wide range of substrates, yielding moderate to good yields under mild conditions using air as an external green oxidant. [ABSTRACT FROM AUTHOR]

In this work, we have developed an electrochemical method to prepare 2-aminobenzoxazole by using acetic acid as an electrolyte. The key benefits of this method are being cleaner reaction pattern with minimum impurity formation, no metal catalyst used, high atom economy, robust, scalable and having a broad substrate scope. Previously, electrochemical conversions were reported with the addition of a supporting electrolyte such as tetrabutyl ammoniumbromide, sodium iodide and lithium perchlorate, but in this conversion we have removed the use of all supporting electrolytes and we have used acetic acid, which plays a dual role of opening the benzoxazole moiety and works as an electrolyte. All these electrochemical conversions were done on a electrochemical reactor prepared through a 5v mobile charger having a output current density of 0.35A.cm−2. Various pharmaceutically relevant secondary amines are coupled with benzoxazole in high yield by using this set-up. All the conversions were done at room temperature and total conversion observed in 6 h. The scale of the conversion ranges from milligram to gram. Active intermediate of Suvorexant, a medicine for insomnia, was prepared by using this method. [ABSTRACT FROM AUTHOR]

The base‐promoted reaction of 2‐halonitro‐ or 1,2‐dihalobenzenes with anthranilamide reported by Cao, Ma et al. (Synthesis2013, 45, 111) was reinvestigated. Some of the products reported, which have been identified as dibenzodiazepinones, are actually benzoxazole derivatives. In this paper, the correct structures of these products were established and confirmed by independent synthesis. For four other products, the supposed structures were found to be incompatible with the dibenzodiazepinones that were synthesized by the reliable method used in this work. [ABSTRACT FROM AUTHOR]

Monomeric titanium [C48H62N2O6Ti] (1) and zirconium [C48H62N2O6Zr] (2) complexes were synthesized by combining the monoanionic salicylbenzoxazole pro‐ligand 2‐(5‐X‐benzoxazol‐2‐yl)‐6‐R1‐4‐R2‐phenol, LH (R1, R2, X = tBu, tBu, H, respectively) with Ti(OiPr)4 or Zr(OiPr)4∙(iPrOH) in a 2:1 stoichiometric ratio. Controlled hydrolysis of the monomeric Ti complex with deionized water yielded a new unusual hexanuclear titanium complex [C126H144N6O21Ti6] (3). In addition, the cage formed in this complex 3 was surrounded by all‐oxygen and penta‐coordinated Ti(IV) atoms, which leads to an hexanuclear drum‐shaped Ti complex 3 with a trigonal‐bipyramidal geometry at the metal center. The catalytic activity of these complexes toward ring‐opening polymerization (ROP) of ε‐caprolactone (ε‐CL) and rac‐lactide (rac‐LA) was studied. All these complexes showed moderate to good catalytic activity without using any co‐catalyst additives. Single‐site zirconium alkoxide 2 showed the best catalytic activity and was able to convert 400 units of ε‐CL or rac‐LA into the polymer product in high yield (≥90%) within 1 hour under solvent‐free conditions. The obtained polymers showed good control in molecular weight (Mn = 46.2–6.3 kg/mol) and molecular weight distributions (MWD's = 1.37–1.15). The polymerization of rac‐LA by 2 yielded iso‐enriched polylactide (Pm = 0.60). [ABSTRACT FROM AUTHOR]

Inactivation of the LKB1 tumor suppressor is a frequent event in non-small cell lung carcinoma (NSCLC) leading to the activation of mTOR complex 1 (mTORC1) and sensitivity to the metabolic stress inducer phenformin. In this study, we explored the combinatorial use of phenformin with the mTOR catalytic kinase inhibitor MLN0128 as a treatment strategy for NSCLC bearing comutations in the LKB1 and KRAS genes. NSCLC is a genetically and pathologically heterogeneous disease, giving rise to lung tumors of varying histologies that include adenocarcinomas and squamous cell carcinomas (SCC). We demonstrate that phenformin in combination with MLN0128 induced a significant therapeutic response in KRAS/LKB1-mutant human cell lines and genetically engineered mouse models of NSCLC that develop both adenocarcinomas and SCCs. Specifically, we found that KRAS/LKB1-mutant lung adenocarcinomas responded strongly to phenformin + MLN0128 treatment, but the response of SCCs to single or combined treatment with MLN0128 was more attenuated due to acquired resistance to mTOR inhibition through modulation of the AKT-GSK signaling axis. Combinatorial use of the mTOR inhibitor and AKT inhibitor MK2206 robustly inhibited the growth and viability of squamous lung tumors, thus providing an effective strategy to overcome resistance. Taken together, our findings define new personalized therapeutic strategies that may be rapidly translated into clinical use for the treatment of KRAS/LKB1-mutant adenocarcinomas and squamous cell tumors.

We previously reported that i) a Western diet increased levels of unsaturated lysophosphatidic acid (LPA) in small intestine and plasma of LDL receptor null (LDLR(-/-)) mice, and ii) supplementing standard mouse chow with unsaturated (but not saturated) LPA produced dyslipidemia and inflammation. Here we report that supplementing chow with unsaturated (but not saturated) LPA resulted in aortic atherosclerosis, which was ameliorated by adding transgenic 6F tomatoes. Supplementing chow with lysophosphatidylcholine (LysoPC) 18:1 (but not LysoPC 18:0) resulted in dyslipidemia similar to that seen on adding LPA 18:1 to chow. PF8380 (a specific inhibitor of autotaxin) significantly ameliorated the LysoPC 18:1-induced dyslipidemia. Supplementing chow with LysoPC 18:1 dramatically increased the levels of unsaturated LPA species in small intestine, liver, and plasma, and the increase was significantly ameliorated by PF8380 indicating that the conversion of LysoPC 18:1 to LPA 18:1 was autotaxin dependent. Adding LysoPC 18:0 to chow increased levels of LPA 18:0 in small intestine, liver, and plasma but was not altered by PF8380 indicating that conversion of LysoPC 18:0 to LPA 18:0 was autotaxin independent. We conclude that i) intestinally derived unsaturated (but not saturated) LPA can cause atherosclerosis in LDLR(-/-) mice, and ii) autotaxin mediates the conversion of unsaturated (but not saturated) LysoPC to LPA.

The ceramides are a family of bioactive lipid-derived messengers involved in the control of cellular senescence, inflammation, and apoptosis. Ceramide hydrolysis by acid ceramidase (AC) stops the biological activity of these substances and influences survival and function of normal and neoplastic cells. Because of its central role in the ceramide metabolism, AC may offer a novel molecular target in disorders with dysfunctional ceramide-mediated signaling. Here, a class of benzoxazolone carboxamides is identified as the first potent and systemically active inhibitors of AC. Prototype members of this class inhibit AC with low nanomolar potency by covalent binding to the catalytic cysteine. Their metabolic stability and high in vivo efficacy suggest that these compounds may be used as probes to investigate the roles of ceramide in health and disease, and that this scaffold may represent a promising starting point for the development of novel therapeutic agents.

High-risk neuroblastoma often develops resistance to high-dose chemotherapy. The mTOR signaling cascade is frequently deregulated in human cancers and targeting mTOR signaling sensitizes many cancer types to chemotherapy. Here, using a panel of neuroblastoma cell lines, we found that the mTOR inhibitor INK128 showed inhibitory effects on both anchorage-dependent and independent growth of neuroblastoma cells and significantly enhanced the cytotoxic effects of doxorubicin (Dox) on these cell lines. Treatment of neuroblastoma cells with INK128 blocked the activation of downstream mTOR signaling and enhanced Dox-induced apoptosis. Moreover, INK128 was able to overcome the established chemoresistance in the LA-N-6 cell line. Using an orthotopic neuroblastoma mouse model, we found that INK128 significantly inhibited tumor growth in vivo. In conclusion, we have shown that INK128-mediated mTOR inhibition possessed substantial antitumor activity and could significantly increase the sensitivity of neuroblastoma cells to Dox therapy. Taken together, our results indicate that using INK128 can provide additional efficacy to current chemotherapeutic regimens and represent a new paradigm in restoring drug sensitivity in neuroblastoma.

We have developed the green method for the synthesis of benzoxazoles and benzothiazoles with moderate to good yields using imidazolium chlorozincate (II) ionic liquid supported into Fe3O4 nanoparticles (LAIL@MNP) under solvent-free sonication. The reaction was performed under mild conditions and only produced water as a sole byproduct. The reactions under solvent-free sonication showed advantages of faster reaction rate (30 min) and high yields of the products (up to 90%). Moreover, the LAIL@MNP material was easily separated from the reaction mixture and can be recycled for five consecutive runs with a slight decrease in its catalytic performance (from 82 to 73%).

A series of copper(II) complexes of 2-imino-2H-chromen-3-yl-1,3,5-triazines 2a-h, 3-(benzoxazol-2-yl)-2H-chromen-2-imines 4a-b, and 3-(benzothiazol-2-yl)-2H-chromen-2-imines 6a-c were obtained by reacting of appropriate 2-iminocoumarin ligands L1a-h, L3a-b, and L5a-c with 3-fold molar excess of copper(II) chloride. The structure of these compounds was confirmed by IR spectroscopy, elemental analysis, and single-crystal X-ray diffraction data (2f, 2g, 2h, and 6c). All the synthesized complexes were screened for their activity against five human cancer cell lines: DAN-G, A-427, LCLC-103H, SISO, and RT-4 by using a crystal violet microtiter plate assay and relationships between structure and in vitro cytotoxic activity are discussed. The coordination of 2-iminocoumarins with copper(II) ions resulted in complexes 2a-h, 4a-b, and 6a-c with significant inhibitory properties toward tested tumor cell lines with IC50 values ranging from 0.04 μM to 15.66 μM. In comparison to the free ligands L1a-h, L3a-b, and L5a-c, the newly prepared Cu(II) complexes often displayed increased activity. In the series of copper(II) complexes of 2-imino-2H-chromen-3-yl-1,3,5-triazines 2a-h the most potent compound 2g contained a 4-phenylpiperazine moiety at position 6 of the 1,3,5-triazine ring and an electron-donating diethylamino group at position 7′ of the 2-iminocoumarin scaffold. Among the Cu(II) complexes of 3-(benzoxazol-2-yl)-2H-chromen-2-imines 4a-b and 3-(benzothiazol-2-yl)-2H-chromen-2-imines 6a-c the most active was benzoxazole-2-iminocoumarin 4b that also possessed a diethylamino group at position 7′ of the 2-iminocoumarin moiety. Moreover, compound 4b was found to be the most prominent agent and displayed the higher potency than cisplatin against tested cell lines.

An acetic acid promoted electrochemical synthesis of benzazoles, benzimidazoles, benzthiazoles and benzoxazoles, is reported. The method offers large substrate scope, good functional group tolerance, while using cheap electrolyte. The method uses acetic acid as the electrolyte which has a better solubility in methanol, hence the reaction time is less and product formation is observed in high yield without much side product. This electrochemical method is further utilised to synthesise thiabendazole, fuberidazole, chlormidazole and advance intermediates of bilastine and clemizole in good yields. [ABSTRACT FROM AUTHOR]

Methods of synthesis have been developed to obtain new spiropyrans of the indoline series with semipermanent merocyanines bearing the 5-dimethylamino group in the indoline part and diphenyloxazole, benzoxazole and benzothiazole moieties in the naphthopyran part. In solution, the obtained compounds show both positive and negative photochromism. Photo-controlled bipolar absorption switches based on dimethylamino-substituted spiropyrans have been proposed. Tuning of the characteristics of such switches can be performed both by the structural design of the spiropyran molecules and by the parameters of the medium. [ABSTRACT FROM AUTHOR]

Diesel oil sorption capacities (DOSCs) of polybenzoxazole/polyvinylidene fluoride nanofiber mats with four different groups (‐O‐, ‐S‐S‐, phenylene and diphenylene) in the main chain structures were investigated. Different experimental duration and diesel‐oil/tap‐water volume ratio pairs were used for diesel oil sorption. No degradation was observed in the nanofiber mat structures after diesel oil sorption. The characterizations of polybenzoxazole (PBO) nanofibers with high diesel oil selectivity were performed by scanning electron microscopy, atomic force microscopy, Fourier transform infrared spectroscopy, x‐ray diffraction, thermal gravimetric analysis, differential scanning calorimetry, Brunauer–Emmett–Teller (BET), and contact angle measurement analysis. According to the result of characterizations, superoleophilic and superhydrophobic nanofiber mats show high water contact angle value in the range of 132–140∘ and show high separation efficiency. In this study, we integrated ensemble gradient boosting model (XGBoost) to predict the DOSC of sorbent nanofiber and obtain an optimal set of conditions to maximize the DOSC. The predicted PBO‐E sorbent at the 0.5 ratio of diesel‐oil/tap‐water measured at the end of the 3rd minute showed the most reliable and stable diesel oil sorption with at least 9.39 and at most 12.33 g/g sorbent with 95% of confidence. [ABSTRACT FROM AUTHOR]

2‐Aryl/heteroaryl‐substituted benzoxazoles are important heterocyclic motifs extensively found in several bioactive molecules, pharmaceuticals and natural products. In view of the importance of these compounds, there is need to develop easiest and simplest synthetic routes. The motive of this current work is to conduct the direct C2‐arylation reaction on benzoxazole with various cross‐coupling partners like aryl/heteroaryl halide/carboxylic acid/diazonium tetrafluoroborate/sulfonyl chloride/boronic acids in the presence of different symmetrical and unsymmetrical Pd‐PEPPSI (pyridine‐enhanced pre‐catalyst preparation by stabilization initiation) catalysts via C (sp2)–C (sp2) bond formation. Compared with other coupling partners, boronic acids coupled with benzoxazole very efficiently in the presence of sterically and electronically tunable bulky1,3‐bis(N,N′‐2,4,6‐triisopropylbenzyl)benzimidazolium‐Pd‐PEPPSI complex in open air to offer the corresponding C2‐aryl/heteroaryl benzoxazole compounds. Further, it is worthy to mention that there is no need of any external oxidant/ligand/additive for the complete conversion of starting molecules to products. The reactions progressed successfully with a wide range of substrate scope and attained the products in good to excellent yields in a short reaction time in ethanol/water (1:1) medium. Greatly, catalysts can be recovered and reused for few cycles with significant reactivity. [ABSTRACT FROM AUTHOR]

Searching for new drugs is still a challenge for science, mainly because of civilization development and globalization which promote the rapid spread of diseases, which is particularly dangerous in the case of infectious ones. Moreover, readily available already known antibiotics are often overused or misused, possibly contributing to the increase in the number of multidrug-resistant microorganisms. A consequence of this is the need for new structures of potential drugs. One of them is a benzoxazole moiety, a basic skeleton of a group of fluorescent heterocyclic compounds already widely used in chemistry, industry, and medicine, which is also present in naturally occurring biologically active compounds. Moreover, synthetic benzoxazoles are also biologically active. Considering all of that, a large group of non-proteinogenic amino acids based on 3-(2-benzoxazol-5-yl)alanine skeleton was studied in search for new antimicrobial and anticancer agents. Screening tests revealed that antibacterial potential of 41 compounds studied is not very high; however, they are selective acting only against Gram-positive bacteria (B. subtilis). Moreover, almost half of the studied compounds have antifungal properties, also against pathogens (C. albicans). Most of studied compounds are toxic to both normal and cancer cells. However, in a few cases, toxicity to normal cells is much lower than for cancer cells indicating these compounds as future anticancer agents. The research carried out on such a large group of compounds allowed to establish a structure–activity relationship which enables to select candidates for further modifications, necessary to improve their biological activity and obtain a new lead structure with potential for therapeutic use. [ABSTRACT FROM AUTHOR]

In this study, new fused triazolo-thiadiazoles (4a-o) were synthesized via methyl 2-[bromo(phenyl)methyl]-1,3-benzoxazole-5-carboxylate. The structure of novel derivatives was recognized on the basis of spectral data results and screened their anticonvulsant action by means of maximal electroshock seizure (MES) and subcutaneous pentylenetetrazol (scPTZ) procedures. Minimal motor studies were completed by a rotarod method. Compounds 4e, 4g, 4j, 4l, 4m and 4n showing better anticonvulsant action corresponding to hydrophobicity. Other molecules remained fewer lipophilic and have less effectiveness. Most of the compounds positively tolerable the rotarod test deprived of motor deficiency. In conclusion, the prepared derivatives with distal aryl moiety exhibited higher lipophilic character and lead to improved pharmacological achievement, which can be a forthcoming promise. [ABSTRACT FROM AUTHOR]

Transition metal‐catalyzed C−H bond activation has proved to be a powerful weapon for the synthesis and functionalization of privileged class of heterocycles. The 2‐aryl benzoazole (benzothiazoles, benzoxazoles and benzimidazoles) derivatives have surfaced in the scientific community with their potential applications in medicinal chemistry, agrochemistry and material science. The contribution of C−H activation strategies towards the functionalization of relevant 2‐aryl benzoazoles has been amenable in the drug discovery process. This review envelopes a decade account of the C−H activation strategies adopted for the functionalization of 2‐aryl benzoazoles. [ABSTRACT FROM AUTHOR]

Benzoxazoles extensively exist in biologically active compounds, natural products, pharmaceuticals and functional materials. Thus, facile and green synthesis of such valuable compounds from easily available substrates will make a contribution to drug, material, and fine chemistry. A method for the synthesis of benzoxazoles from catechols, aldehydes and ammonium acetate is developed using NaIO4 as oxidant under metal‐ and additive‐free conditions. A broad range of benzoxazoles including some fluorescent whitening agents, JTP‐426467 and tafamidis analogues are synthesized in 56–95% yields with outstanding functional group tolerance. Mechanistic investigations suggest that an interesting o‐iminocyclohexa‐diene alcohol intermediate is involved in the reaction. These salient features of the protocol make it an alternative for the synthesis of benzoxazoles. [ABSTRACT FROM AUTHOR]

A novel approach has been developed to construct benzoxazoles and similar N- and S-containing heterocycles from their corresponding isothiocyanates and o-substituted anilines via cyclodesulfurization. The reaction was found to proceed via in situ formation of disubstituted thiourea, followed by intramolecular cyclodesulfurization to yield the desired benzazole. Cyclodesulfurization was achieved by the application of safer and inexpensive oxidant, hydrogen peroxide (H2O2) under microwave irradiation. In addition to the safe environmental footprints that hydrogen peroxide exhibits, the absence of any base or additive makes it a mild and green synthetic strategy. This method contributes to the field of metal- and base-free cyclodesulfurization, thereby aids the synthesis of pharmacologically potent heterocyclic scaffolds. [ABSTRACT FROM AUTHOR]

Benzothiazole and its derivatives have been manifested as an optimistic scaffold due to their immense biological importance. Several methodologies have been reported as modifications after the first report of 2‐substituted benzothiazole. Among them, many involve a shift from the conventional synthetic approach by utilizing different catalytic systems. Moreover, synthetic methodologies focused on improvements in terms of product yield, reaction duration, use of environmentally benign conditions and simplified workup procedures predominate among the recently developed approaches. Solid‐phase organic synthesis received considerable attention with the pioneering findings of Merrifield's solid‐phase peptide synthesis in 1963. A diverse range of organic, inorganic and organic‐inorganic substances have been utilized as polymeric solid supports in various catalytic applications. The recyclability and reusability of the immobilized catalysts over consecutive cycles establish them as an attractive alternative over conventional catalytic systems from the environment as well as industrial perspective. The present review summarizes the recent developments in the environmentally benign synthesis of benzothiazole derivatives using supported reagents. Different solid supports along with their catalytic application, mechanistic perspective and substrate tolerance have been discussed comprehensively. [ABSTRACT FROM AUTHOR]

We reported herein a facile tandem synthesis of new bis(thiazoles) utilizing the appropriate thieno[2,3-b]thiophene-linked bis(α-bromoketones). Thus, two equivalents of each of the appropriate acetonitriles were reacted with phenyl isothiocyanate and potassium hydroxide in DMF under stirring at rt for 6 h. To the prior mixture, one equivalent of the appropriate bis(α-bromoketones) was added and stirring was continued for 8 h to give the target bis(thiazoles). Furthermore, we examined the synthesis of new bis(thiazoles) linked to different heterocyclic units. These hybrids were prepared using a similar tandem protocol and utilizing the appropriate acetonitriles, linked to thiazole, benzothiazole, benzoxazole or benzimidazole units. The in vitro antibacterial efficacy of the new hybrids was assessed using the reference Ciprofloxacin (MIC values of 2.7 µM). New hybrids linked to benzoxazole units displayed the best antibacterial efficacy against S. aureus, S. mutans, E. coli, and K. pneumonia strains with MIC values of 1.6–3.3 µM. [ABSTRACT FROM AUTHOR]