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In the present study a series of ethyl 4-(substituted)-2-methyl-4H-benzo[4,5]thiazolo[3,2-a]pyrimidine-3-carboxylate and ethyl 4-(substituted)-8-methoxy-2-methyl-4H-benzo[4,5]thiazolo[3,2-a]pyrimidine-3-carboxylate have been synthesized and evaluated for their preliminary antibacterial, antifungal, antimycobacterial, antioxidant and antimalarial activity. Among all the synthesized derivatives some of the compounds exists good biological activity which is similar to that of standard drugs. These facts make the compounds interesting candidates for further evaluation of their efficacy in the treatment microbial, tubercular and malarial disease. [ABSTRACT FROM AUTHOR]

A series of pleuromutilin analogs containing substituted benzoxazole were designed, synthesised, and assessed for their antibacterial activity both in vivo and in vitro. The MIC of the synthesised derivatives was initially assessed using the broth dilution method against four strains of Staphylococcus aureus (MRSA ATCC 43300, S. aureus ATCC 29213, clinical isolation of S. aureus AD3 and S. aureus 144). Most of the synthesised derivatives displayed prominent in vitro activity (MIC ≤ 0.5 µg/mL). Compounds 50 and 57 exhibited the most effective antibacterial effect against MRSA (MIC = 0.125 µg/mL). Furthermore, the time-kill curves showed that compounds 50 and 57 had a certain inhibitory effect against MRSA in vitro. The in vivo antibacterial activity of compound 50 was evaluated further using a murine thigh model infected with MRSA (–1.24 log10CFU/mL). Compound 50 exhibited superior antibacterial efficacy to tiamulin. It was also found that compound 50 did not display significant inhibitory effect on the proliferation of RAW 264.7 cells. Molecular docking study revealed that compound 50 can effectively bind to the active site of the 50S ribosome (the binding free energy −7.50 kcal/mol). [ABSTRACT FROM AUTHOR]

A new series of 2-aminobenzothiazole hybrids linked to thiazolidine-2,4-dione 4a–e, 1,3,4-thiadiazole aryl urea 6a–d, and cyanothiouracil moieties 8a–d was synthesised. The in vitro antitumor effect of the new hybrids was assessed against three cancer cell lines, namely, HCT-116, HEPG-2, and MCF-7 using Sorafenib (SOR) as a standard drug. Among the tested compounds, 4a was the most potent showing IC50 of 5.61, 7.92, and 3.84 µM, respectively. Furthermore, compounds 4e and 8a proved to have strong impact on breast cancer cell line with IC50 of 6.11 and 10.86 µM, respectively. The three compounds showed a good safety profile towards normal WI-38 cells. Flow cytometric analysis of the three compounds in MCF-7 cells revealed that compounds 4a and 4c inhibited cell population in the S phase, whereas 8a inhibited the population in the G1/S phase. The most promising compounds were subjected to a VEGFR-2 inhibitory assay where 4a emerged as the best active inhibitor of VEGFR-2 with IC50 91 nM, compared to 53 nM for SOR. In silico analysis showed that the three new hybrids succeeded to link to the active site like the co-crystallized inhibitor SOR. [ABSTRACT FROM AUTHOR]

A series of new liquid crystal compounds with negative dielectric anisotropy was synthesised by regulating the orientation of the substituents on the benzoxazole ring, namely, 5–4-(2-(4-(alkoxy)phenyl)-2,3-difluorophenyl)benzo[d]oxazole derivatives (nPP(2,3)FO). These compounds mainly display enantiotropic nematic mesophases in the ranges of 8.62–16.09°C (heating process) and 23.98–30.32°C (cooling process), moderate birefringence (Δn) ranging from 0.25–0.32 (DFT theoretical calculation) and 0.22–0.28 (experimental measurement), as well as negative dielectric anisotropy (Δɛ) ranging from −2.77 to −2.94. These characterises are ascribed to the larger perpendicular dipole moments and orientation angles of benzoxazole. This work provides new ideas for the rational design of negative dielectric anisotropy liquid crystals. [ABSTRACT FROM AUTHOR]

New 2-(4-(fluorosulfonyloxy)phenyl)benzoxazole (2) was synthesized through the SuFEx click reaction in a two-chamber reactor. The effect of silylation on the yield of the target compound was investigated. The fluorescent properties of compound 2 were determined using experimental and computational methods. [ABSTRACT FROM AUTHOR]

BackgroundPemafibrate is a novel, selective peroxisome proliferator-activated receptor α modulator (SPPARMα). In mice, Pemafibrate improved the histological features of non-alcoholic steatohepatitis (NASH). In patients with dyslipidaemia, it improved serum alanine aminotransferase (ALT).AimsTo evaluate the efficacy and safety of Pemafibrate in patients with high-risk, non-alcoholic fatty liver disease (NAFLD).MethodsThis double-blind, placebo-controlled, randomised multicentre, phase 2 trial randomised 118 patients (1:1) to either 0.2 mg Pemafibrate or placebo, orally, twice daily for 72 weeks. The key inclusion criteria included liver fat content of ≥10% by magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF); liver stiffness of ≥2.5 kPa, by magnetic resonance elastography (MRE); and elevated ALT levels. The primary endpoint was the percentage change in MRI-PDFF from baseline to week 24. The secondary endpoints included MRE-based liver stiffness, ALT, serum liver fibrosis markers and lipid parameters.ResultsThere was no significant difference between the groups in the primary endpoint (-5.3% vs -4.2%; treatment difference -1.0%, P = 0.85). However, MRE-based liver stiffness significantly decreased compared to placebo at week 48 (treatment difference -5.7%, P = 0.036), and was maintained at week 72 (treatment difference -6.2%, P = 0.024), with significant reduction in ALT and LDL-C. Adverse events were comparable between the treatment groups and therapy was well tolerated.ConclusionsPemafibrate did not decrease liver fat content but had significant reduction in MRE-based liver stiffness. Pemafibrate may be a promising therapeutic agent for NAFLD/NASH, and also be a candidate for combination therapy with agents that reduce liver fat content. ClinicalTrials.gov, number: NCT03350165.

ObjectiveHepatocellular carcinoma (HCC) is the most common type of primary liver cancer with limited treatment options. Cabozantinib, an orally bioavailable multikinase inhibitor is now approved by Food and Drug Administration (FDA) for HCC patients. We evaluated the therapeutic efficacy of cabozantinib, either alone or in combination, in vitro and in vivo.DesignHuman HCC cell lines and HCC mouse models were used to assess the therapeutic efficacy and targeted molecular pathways of cabozantinib, either alone or in combination with the pan-mTOR inhibitor MLN0128 or the checkpoint inhibitor anti-PD-L1 antibody.ResultsCabozantinib treatment led to stable disease in c-Met/β-catenin and Akt/c-Met mouse HCC while possessing limited efficacy on Akt/Ras and c-Myc liver tumours. Importantly, cabozantinib effectively inhibited c-MET and ERK activity, leading to decreased PKM2 and increased p21 expression in HCC cells and in c-Met/β-catenin and Akt/c-Met HCC. However, cabozantinib was ineffective in inhibiting the Akt/mTOR cascade. Intriguingly, a strong inhibition of angiogenesis by cabozantinib occurred regardless of the oncogenic drivers. However, cabozantinib had limited impact on other tumour microenvironment parameters, including tumour infiltrating T cells, and did not induce programmed death-ligand 1 (PD-L1) expression. Combining cabozantinib with MLN0128 led to tumour regression in c-Met/β-catenin mice. In contrast, combined treatment with cabozantinib and the checkpoint inhibitor anti-PD-L1 antibody did not provide any additional therapeutic benefit in the four mouse HCC models tested.Conclusionc-MET/ERK/p21/PKM2 cascade and VEGFR2-induced angiogenesis are the primary targets of cabozantinib in HCC treatment. Combination therapies with cabozantinib and mTOR inhibitors may be effective against human HCC.

It was first reported almost two decades ago that ligands with azo functions are capable of accepting electron(s) upon coordination to produce azo-anion radical complexes, thereby exhibiting redox non-innocence. Over the past two decades, there have been numerous reports of such complexes along with their structures and diverse characteristics. The ability of a coordinated azo function to accept one or more electron(s), thereby acting as an electron reservoir, is currently employed to carry out electron transfer catalysis since they can undergo redox transformation at mild potentials due to the presence of energetically accessible energy levels. The cooperative involvement of redox non-innocent ligand(s) containing an azo group and the coordinated metal centre can adjust and modulate the Lewis acidity of the latter through selective ligand-centred redox events, thereby manipulating the capacity of the metal centre to bind to the substrate. We have summarized the list of first row transition metal complexes of iron, cobalt, nickel, copper and zinc with redox non-innocent ligands incorporating an azo function that have been exploited as electron transfer catalysts to effectuate sustainable synthesis of a wide variety of useful chemicals. These include ketazines, pyrimidines, benzothiazole, benzoxazoles, N-acyl hydrazones, quinazoline-4(3)H-ones, C-3 alkylated indoles, N-alkylated anilines and N-alkylated heteroamines. The reaction pathways, as demonstrated by catalytic loops, reveal that the azo function of a coordinated ligand can act as an electron sink in the initial steps to bring about alcohol oxidation and thereafter, they serve as an electron pool to produce the final products either via HAT or PCET processes. [ABSTRACT FROM AUTHOR]

In the present work, mononuclear copper(II) complexes [Cu(L1)Cl](1) and [Cu(L2)Cl](2) having meridional tridentate "NNO" ligands with different substituents have been synthesized and the complexes were characterized by different analytical and spectral techniques, namely FT-IR, NMR, and UV-Vis spectral studies. Molecular structures of complexes 1 and 2 were determined by single-crystal X-ray crystallography. These complexes have been utilized as a catalyst for the synthesis of substituted benzoxazole derivatives under mild conditions. A total of 34 benzoxazole derivatives having different substituents were prepared. The mechanism of this multicomponent reaction, catalysed by complexes 1 and 2, was investigated and the proposed reaction mechanism was based on H-atom abstraction by the phenoxyl radical complex. [ABSTRACT FROM AUTHOR]

The design and research of luminescent and volatile organic compound (VOC) fluorescent sensing materials are of great significance and challenge. We report herein the ligand substitution reaction and VOC sensing of new heteroleptic [Cu(P˄P)N2]+ type copper(I) complexes. Firstly, three new complexes 1–3 were designed by utilizing a chelate diphosphine ligand 4,5‐bis(diphenylphosphino)‐9,9‐dimethylxanthene (Xantphos) and synthesized by the substitution reaction of different N‐containing ligands of 4‐PBO (1), 3‐PBO (2), and 4,4′‐Bipy (3) (4‐PBO = 2‐(4′‐pyridyl)‐benzoxazole, 3‐PBO = 2‐(3′‐pyridyl)‐benzoxazole, 4,4′‐Bipy = 4,4′‐bipyridine), respectively. Three complexes were characterized by elemental analysis, spectroscopic analysis (IR, UV–Vis), single‐crystal X‐ray diffraction (SCXRD), and photoluminescence study. The SCXRD study revealed that complexes 1 and 2 both exhibit a molecular structure with tetrahedral copper(I) complex cation and hexafluorophosphate anion, while complex 3 differs in that its cation is a binuclear copper(I) structure bridged by 4,4′‐bipyridine. Three complexes 1–3 present supramolecular ribbon, supramolecular dimer, and supramolecular framework structure, respectively. Some differences of their UV–Vis absorption spectra were explained by TD‐DFT calculation and wavefunction analysis. It is found that 1 has an abnormal luminescence blue shift, and a luminescence mechanism through the high‐energy T2 excited state is proposed by TD‐DFT calculation. Based on 3, a fluorescent test strip was developed, and its fast and selective fluorescent sensing of pyridine vapor through quenching mechanism was successfully realized. The fluorescent quenching mechanism of the material was also studied, and it was proposed that the quenching should be attributed to the photoinduced electron transfer (PET) mechanism. [ABSTRACT FROM AUTHOR]

A novel sterically hindered o-benzoquinone 4,6-di-tert-butyl-3-(5,7-di-tert-butylbenzooxazole-2-yl)-o-benzoquinone containing a benzoxazole moiety is prepared. The interaction of this quinone with Cu(0) yielded a cubane copper(II) complex with a Cu4O4 core. Molecular and crystal structures of the o-quinone (CCDC 2269708) and the copper complex (CCDC 2269709) are determined by XRD. [ABSTRACT FROM AUTHOR]

Synthesised N-substituted heterocyclic derivatives have ubiquitous applications in fine chemicals, pharmaceuticals, organic electronic materials, and agrochemicals. Numerous reports of photocatalytic C–N coupling in aid of a 5 W visible light source are documented in the literature which facilitates the cost reducibility, reusability, and promising methods for reaction. In this present work, we have designed and synthesised a benzimidazole-based sulphonic acid functionalized porphyrin photocatalyst (BSAFPPc) and confirmed by analytical techniques such as FT-NMR, FT-IR, and SEM/EDX. The BSAFPPc demonstrated an optical energy gap of 1.12 eV by using DRS. Further, the acidic potential was scrutinized by the Hammett acidity function which is H0 = 0.99. The BSAFPPc was used for the C–N coupling of morpholine, and inactivated aryl halides comprising electron-donating (–NH2, –OMe, –CH3) and withdrawing groups (–CHO, –NO2). This photocatalytic reaction produced an excellent practical yield from 60 to 90%. Further, the scope was extended to benzimidazole, pyrrole, indole and 1,2,4-triazole. The reaction has been experimented in an in-house homemade reactor system in a presence of a 5 W visible light source in an additive-free environment at ambient conditions. The photocatalyst was durable up to six photocatalytic cycles. The photocatalyst maintained its heterogenous nature which was asserted by the leaching test. [ABSTRACT FROM AUTHOR]

The green synthesis of sulfur-containing compounds via the use of CO2 as a C1 feedstock to build C–S bonds is an attractive topic. Although a few implementations for this route have been reported, the transformation of CO2 at ambient conditions remains a great challenge. In this work, a novel benoxazolone-based ionic liquid (i.e., tetrabutylphosphonium benoxazolone, [P4444][Benoxa]) was discovered, which could efficiently catalyze the synthesis of benzothiazoles via the cyclization of 2-aminothiophenols with CO2 in the presence of hydrosilanes at atmospheric pressure and room temperature (e.g., 30 °C, 0.1 MPa). The catalytic protocol was applicable to various 2-aminothiophenols bearing electron-withdrawing or electron-donating substituents, affording the corresponding benzothiazoles in good-to-excellent yields. To the best of our knowledge, this is the first example of the synthesis of benzothiazoles using CO2 under solvent-free and ambient conditions. [ABSTRACT FROM AUTHOR]

In this work, layered zirconium phosphates were synthesized via a reflux method and calcined at different temperatures (200, 400, and 600°C). The catalytic activity of the prepared solids was tested in the condensation of o-phenylenediamine and o-aminothiophenol with various aromatic aldehydes. The reaction conditions were optimized taking into account some parameters that control the reaction, namely the nature and volume of the solvent and the mass of the catalyst. The results showed that solid ZrP-200 (layered zirconium phosphate calcined at 200°C) is the best performing catalyst for this reaction, because it has good catalytic activity and can be reused for at least five cycles with only a slight decrease in catalytic activity. In addition, a possible mechanism for the synthesis of benzimidazoles and benzothiazoles over ZrP-200 was proposed and discussed at the end of this study. [ABSTRACT FROM AUTHOR]

An efficient, highly convergent route for the synthesis of novel fourteen single isomer derivatives of ethyl-2-methyl-4-(pyridin-2-yl)-4H-benzo[4,5]thiazolo[3,2-a]pyrimidine-3-carboxylate have been developed by one-pot, three-component reaction between pyridine 2-aldehyde, β-ketoester and various derivatives of 2-amino benzothiazole in the presence of D-(+)-10-camphorsulphonic acid (D-(+)-10-CSA) as an effective chiral acid catalyst. Under the optimized conditions with 20 mol% catalyst loading, a wide range of optically active 4H-pyrimido[2,1-b]benzothiazole derivatives were obtained in good yields (up to 82%) with good to excellent enantioselectivities (84-99%ee). Their structures were elucidated by various spectroscopic methods such as 1H-NMR, 13C-NMR, Chiral HPLC, mass and elemental analysis. The attractive feature of this approach is one-pot synthesis, good yield, environment benign, mild reaction condition, simple, efficient, excellent stereoselectivity, water soluble catalyst and easy workup. All the final scaffolds have been screened for antibacterial activity. Among them, 4a', 4c', 4d', 4e', 4f', 4g', 4j',4m' and 4n' were proven to possess enhanced antibacterial properties as compared to the standard drug. [ABSTRACT FROM AUTHOR]

Herein, we have reported the facile synthesis of various benzimidazole/benzothiazole by using DBU-iodine-iodide as a green and simple catalyst. The R3NHI3 complexes have been formed by reacting an aqueous mixture of ammonium iodide and molecular iodine with the aqueous solution of amine. The structure of R3NHI3 complexes has been confirmed by spectroscopic techniques. The prepared amine-iodine complexes were screened as a catalysts in the synthesis of benzimidazole/benzothiazoles. Among the screened catalysts DBUHI3 complex has been found as most efficient catalyst. The synthesis of benzimidazoles and benzothiazoles has been achieved with the reaction of ophenylene diamine/o-aminothiophenol and various substituted aryl aldehyde using DBUHI3 as a catalyst. The present protocol has offered some advantages over other reported protocols such as the mild reaction condition, commercially available precursors, inexpensive catalyst, short reaction time, the broad scope of the substrate, high yield, simple isolation of the product and environmentally benign method. [ABSTRACT FROM AUTHOR]

Apoptosis plays a crucial role in cancer pathogenesis and drug resistance. BCL-2 family of enzymes is considered as one of the key enzymes which is involved in apoptosis. When there is disruption in the balance between anti-apoptotic and pro-apoptotic members of the BCL-2 family apoptosis is dysregulated in the affected cells. Herein, 33 novel benzothiazole-based molecules 7a-i, 8a-f, 9a-b, 12a-e, 13a-d, 14a,b, and 17a-j were designed, synthesized and tested for their BCL-2 inhibitory activity. Scaffold hopping strategy was applied in designing of the target compounds. Compounds 13c and 13d showed the highest activity with IC50 values equal to 0.471 and 0.363 µM, respectively. Molecular docking studies of the synthesized compounds showed comparable binding interactions with the lead compound. Structure activity relationship study was performed to show the effects of structural modifications on the inhibitory activities on BCL-2. [ABSTRACT FROM AUTHOR]

Naturally, occurring as well as synthetic nitrogen and oxygen containing heterocyclic compounds like benzoxazoles and its derivatives have found to be playing a vital role in the Pharmaceutical, agriculture; polymer, material science and they also exhibits series of significant antimicrobial activities. In the last decade, an organic transformation has found abundant application of nanotechnology and nanoscience can aid design catalyst with excellent efficiency, selectivity and stability. Academics and industry have recently shown a lot of interest in the application of nanocatalysts, a field that is expanding significantly, to create sustainable and environmentally friendly processes for the synthesis of benzoxazole derivatives with multi‐component reactions (MCRs). Nanocatalyst reactions have advantages over conventional catalyst reactions because of the interaction of chemical reactants made possible by a high surface area ratio, simple purification, low catalyst loading, high atom economy, inexpensiveness, short reaction time, better yield, and recyclability of the nanocatalysts. In this review article, mainly focus is on the nanocatalysts fabrications, characterizations and their applications for the synthesis of benzoxazoles moiety during the last decennary (2011 to 2022). [ABSTRACT FROM AUTHOR]

The synthesis of novel mono‐azo benzothiazole derivatives using 3‐Diethylaminophenol (3‐DEAP) as a common coupling component is an electrophilic substitution reaction that was influenced by the positive mesomeric effect (+M effect) under appropriate experimental conditions. Various spectroscopic and analytical methods, including UV‐vis, fluorescence, FT‐IR, (1H and 13C) NMR, and HRMS, were used to confirm the structural characteristics of the synthesized molecules. Further, the Gaussian 09, CAM‐B3LYP/LANL2MB functions are used to predict the quantum chemical characteristics and their molecular electrostatic potential region of all the designed mono‐azo derivatives. Based on the investigations of UV‐Vis, interactions between intramolecular hydrogen bonds were observed in a variety of solvents and polarities, with a maximum in the 508–534 nm range. The gram‐positive and two gram‐negative bacterial strains were utilized for antibacterial activity in order to examine the biological effectiveness of the colourants. The coupling component with benzothiazole derivative showed a 14 mm zone of inhibition against the Gram‐negative bacteria Salmonella typhi. When compared to the standard BHT and EDTA as the positive control, the data from the DPPH and FIC assay technique of the titled compounds showed that all colourants have promising anti‐oxidant capabilities. [ABSTRACT FROM AUTHOR]

(R)‐2‐(4‐(Benzo[d]oxazol‐2‐yl)piperazin‐1‐yl)‐4‐((tetrahydro‐2H‐pyran‐4‐yl)amino)‐6,7‐dihydrothieno[3,2‐d]pyrimidine 5‐oxide (1) and (R)‐2‐(4‐(4‐chlorophenoxy)piperidin‐1‐yl)‐4‐((tetrahydro‐2H‐pyran‐4‐yl)amino)‐6,7‐dihydrothieno[3,2‐d]pyrimidine 5‐oxide (2) are two potent and selective inhibitors of phosphodiesterase type 4 (PDE4). In this manuscript, we report the detailed synthesis of these two compounds labeled with carbon 14 and with stable isotopes. The core (R)‐4‐((tetrahydro‐2H‐pyran‐4‐yl)amino)‐6,7‐dihydrothieno[3,2‐d]pyrimidine 5‐oxide is common in both inhibitors. In the radioactive synthesis, the carbon 14 atom was introduced in the benzoxazole moiety using [14C]carbon disulfide to obtain [14C]‐1 in five steps at a 55% overall yield. [14C]Urea was used to incorporate the carbon 14 atom in two steps in the dihydrothieno[3,2‐d]pyrimidine intermediate, which was then transformed in four more steps to [14C]‐2 at a 30% overall yield. Both compounds were isolated with specific activities higher than 54 mCi/mmol, radio‐ and chemical‐purities higher than 99%, and with excellent enantiomeric excess. In the stable isotope synthesis, [2H8]piperazine was used to prepare [2H8]‐1 in three steps in 72% overall yield, while [13C6]phenol was used to prepare [13C6]‐2 in four steps in 18% overall yield. [ABSTRACT FROM AUTHOR]

A new method has been developed for the synthesis of 2-(1-arylalkyl)-1,3-benzoxazoles by coupling of arylboronic acids with 2-(5-iodo-1H-1,2,3-triazol-1-yl)phenols. The proposed cascade process involves intermediate formation of 2-(1-diazoalkyl)-1,3-benzoxazoles and their reductive C–C coupling with arylboronic acids. The procedure requires no transition metal catalysis and provides up to 67% yield of the target products. [ABSTRACT FROM AUTHOR]

This review presents the applications of BaMnO4 as an efficient oxidizing reagent in oxidation of organic compounds. Using BaMnO4, benzylic, aromatic allylic alcohols, propargylic alcohols, and acyloins were converted to their corresponding carbonyl compounds. Also, oxidations of thiazolines and oxazolines to prepare aromatic thiazol and oxazole heterocycles were performed. Using this oxidant, alcohols were successfully oxidized and participated in tandem oxidation–Wittig reaction with halides. This reagent was also used to oxidative cyc1ization of benzylideneamino anilines, phenols and thiophenols for the synthesis of benzimidazoles, benzoxazoles and benzthiazoles. The oxidative coupling of thiols, 1,4-dihydropyridin derivatives and conversion of thiazolidines to thiazolines and the preparation of symmetrical disulfides were proceeded by this oxidative reagent. Using BaMnO4 in oxidation of organic compounds is more advantageous with respect to traditional manganese based oxidants, more notably with MnO2. [ABSTRACT FROM AUTHOR]

In the absence of Co (II) immobilized on Fe SB 3 sb O SB 4 sb @SiO SB 2 sb -NH SB 2 sb /EP@SAA, the benzimidazole product was obtained in low yield after 2 h, demonstrating that the catalyst is essential for good yields in short reaction times (Table 1, Entry 10). Synthesis of 2-arylsubstituted benzimidazoles using Fe SB 3 sb O SB 4 sb @SiO SB 2 sb -NH SB 2 sb /EP@SAA-Co (II) in EtOH. Fast, simple and high-yield synthesis continues to be a major challenge for synthetic organic chemists. [Extracted from the article]

This study describes the synthesis of 2,5-Bis(3,4-dialkoxy phenyl) Thiazolo[5,4-d} thiazoles (DAITn) (I) and its subsequent structural analysis. These compounds were prepared via reaction of dithio-oxarnidc with the freshly prepared 3,4-dialkoxy benzaldehyde in (DMF). The structure of DAITn (I) was found to have the 3 and 4 positions of the two benzene rings substituted with (OCnH2n+h n=2-5) which equaled to compound M2-M5. The primary methods used for theoretical calculations in this study are quantum mechanics/molecular dynamics simulations based on Density Functional Theory (DFT) and Monte Carlo. The Gaussian09W software's B3LYP hybrid feature and 6-311++G(d,p) basis set were employed in both the gas and aqueous phase for protonated and non-protonated species at the B3LYP level. Electronic structural identifiers were discovered from geometryoptimized structures and correlations between EHOMO (higher occupied molecular orbital energy), ELUMO (lower unoccupied molecular orbital energy), (Eg) bandgap energy, (I) ionization energy, (χ) electronegativity, (ΔN) electron transfer, and (ΔE_(b-d)) back-donation energy were calculated. The Monte Carlo method was used to calculate the adsorption for all identified compounds in this study, and a Fe (110) crystal more stable surface was selected. UV-visible spectroscopy is measuring absorption coefficient, transmittance, and electrical conductivity, and uses a Tauc plot for bandgap energy of the highest absorption peaks. ADTTn molecules with a wide bandgap and a high optical conductivity. Thermodynamic parameters, molecular dynamics simulations, and adsorption energy have been examining inhibitor/surface interactions with greater binding energy leading to stronger interaction and larger negative adsorption energy value indicating a more stable interaction. A four-slab model featuring eighty iron atoms per layer, or one hundred- and ten-unit cells, was used, along with a spline transformation function and a cut-off distance of 1.85 nm for nonbonded interactions. Simulated heating was employed to progressively lower the temperature and search for a low-energy adsorption site. [ABSTRACT FROM AUTHOR]

IntroductionThere are currently no approved targeted therapies for lung squamous-cell carcinoma (LSCC) and KRAS-mutant lung adenocarcinoma (LUAD). About 30% of LSCC and 25% of KRAS-mutant LUAD exhibit hyperactive NRF2 pathway activation through mutations in NFE2L2 (the gene encoding NRF2) or its negative regulator, KEAP1. Preclinical data demonstrate that these tumors are uniquely sensitive to dual inhibition of glycolysis and glutaminolysis via mammalian target of rapamycin (mTOR) and glutaminase inhibitors. This phase 1 study was designed to assess safety and preliminary activity of the mTOR inhibitor MLN0128 (sapanisertib) in combination with the glutaminase inhibitor CB-839 HCl.MethodsPhase 1 dose finding will use the queue-based variation of the 3 + 3 dose escalation scheme with the primary endpoint of identifying the recommended expansion dose. To confirm the acceptable tolerability of the recommended expansion dose, patients will subsequently enroll onto 1 of 4 expansion cohorts (n = 14 per cohort): (1) LSCC harboring NFE2L2 or (2) KEAP1 mutations, or (3) LUAD harboring KRAS/(KEAP1 or NFE2L2) coalterations, or (4) LSCC wild type for NFE2L2 and KEAP1. The primary endpoint of the dose expansion is to determine the preliminary efficacy of MLN0128/CB-839 combination therapy.ConclusionThis phase 1 study will determine the recommended expansion dose and preliminary efficacy of MLN0128 and CB-839 in advanced non-small-cell lung cancer with a focus on subsets of LSCC and KRAS-mutant LUAD harboring NFE2L2 or KEAP1 mutations.

Hepatocellular carcinoma (HCC) is the sixth most common primary cancer with an unsatisfactory long-term survival. Gain of function mutations of PIK3CA occur in a subset of human HCC. Alpelisib, a selective PIK3CA inhibitor, has been approved by the FDA to treat PIK3CA mutant breast cancers. In this manuscript, we evaluated the therapeutic efficacy of alpelisib, either alone or in combination, for the treatment of HCC. We tested alpelisib in mouse HCC induced by hydrodynamic injection of c-Met/PIK3CA(H1047R) (c-Met/H1047R), c-Met/PIK3CA(E545K) (c-Met/E545K), and c-Met/sgPten gene combinations. Alpelisib slowed down the growth of c-Met/H1047R and c-Met/E545K HCC but was ineffective in c-Met/sgPten HCC. Mechanistically, alpelisib inhibited p-ERK and p-AKT in c-Met/H1047R and c-Met/E545K HCC progression but did not affect the mTOR pathway or genes involved in cell proliferation. In human HCC cell lines transfected with PIK3CA(H1047R), alpelisib synergized with the mTOR inhibitor MLN0128 or the CDK4/6 inhibitor palbociclib to suppress HCC cell growth. In c-Met/H1047R mice, alpelisib/MLN0128 or alpelisib/palbociclib combination therapy caused tumor regression. Our study demonstrates that alpelisib is effective for treating PIK3CA-mutated HCC by inhibiting MAPK and AKT cascades. Furthermore, combining alpelisib with mTOR or CDK4/6 inhibitors has a synergistic efficacy against PIK3CA-mutated HCC, providing novel opportunities for precision medicine against HCC.

Two-dimensional (2D) graphene oxide nanosheets serve as an excellent support material for immobilizing metal complexes to deal with the drawbacks of homogeneous catalysis. In this work, we report a magnetically retrievable graphene oxide (MGO) based copper nanocatalytic system that has been efficiently exploited for obtaining a series of pharmaceutically and biologically active benzoxazole scaffolds. The nanocatalyst was designed by covalent immobilization of dehydroacetic acid (DHA) onto a magnetic amino-silanized graphene oxide nanosupport which was accompanied by its metallation with copper acetate. The structure of the synthesized MGO hybrid material (Cu@DHA@APTES@MGO) was characterized by numerous physico-chemical techniques such as transmission electron microscopy (TEM), field emission scanning electron microscopy (FE-SEM), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), vibrating sample magnetometry (VSM), elemental mapping, atomic absorption spectroscopy (AAS), thermogravimetric analysis (TGA), Brunauer–Emmett–Teller (BET) surface area analysis and energy-dispersive X-ray fluorescence spectroscopy (ED-XRF). The fabricated architectures exhibited high efficiency for cyclization of 2-aminophenols and β-diketones with wide substrate scope, excellent functional group tolerance, a higher conversion percentage (>98%) and a high turnover number (TON). The exceptional catalytic activity could be attributed to the 2D architecture of graphene oxide which provides space for trapping of reactants between 2D graphitic overlayers and metal surfaces and the reaction proceeds to afford benzoxazole products with moderate to excellent conversion percentages. Notably, this nanocomposite could be recovered easily through an external magnetic force and reused for multiple runs without any appreciable loss in its catalytic efficacy. [ABSTRACT FROM AUTHOR]

Keywords: iodine; quinazolinones; amino acids; decarboxylation; dimethyl sulfoxide; oxidation EN iodine quinazolinones amino acids decarboxylation dimethyl sulfoxide oxidation 2561 2569 9 07/31/23 20230817 NES 230817 Graph Heteroarenes have remained as the center of attraction in the pharmaceutical industries over the decades. As a part of our continuing interest in the synthesis of novel heterocyclic compounds [41] and iodine-catalyzed method development, [43] we envisioned that quinazolinone derivatives may be prepared by using readily available 2-aminobenzamide derivatives and commercially inexpensive amino acids as coupling partners under iodine-catalyzed conditions. First of all, the amino acid phenylglycine was subjected to the optimum reaction conditions without having the 2-aminobenzamide derivative in the reaction mixture. A large number of quinazolinone derivatives and other related heterocyclic compounds were prepared via oxidative decarboxylation of the amino acids followed by an annulation reaction. [Extracted from the article]

In this work, we focused on synthesizing and assessing novel chitosan-based antibacterial polymers and their nanoparticles by incorporating benzothiazole substituents. The growing resistance to antibiotics has necessitated the search for alternative antimicrobial compounds. This study aimed to synthesize and evaluate chitosan-based polymers and nanoparticles with benzothiazole substituents for their antibacterial properties and toxicity. The benzothiazole derivatives of chitosan and their nanoparticles were synthesized through electrochemical coupling. The in vivo antibacterial efficacy was tested on white rats with induced peritonitis using a microbial suspension containing S. aureus and E. coli. Additionally, in vitro and in vivo toxicity assessments were conducted. The chitosan-based antibacterial systems showed significant in vivo antibacterial activity, surpassing that of unmodified chitosan and commercial antibiotics. Moreover, the toxicity studies revealed low toxicity levels of the synthesized derivatives, which did not differ significantly from native chitosan. The synthesized chitosan-based polymers and nanoparticles demonstrated potent antibacterial activity and low toxicity, highlighting their potential as effective alternatives to traditional antibiotics. Further investigations in pharmacology and preclinical trials are recommended to explore their application in clinical settings. [ABSTRACT FROM AUTHOR]

Herein, a facile, controllable, and versatile method is reported to prepare monodisperse yolk‐shell and yolk‐multishell silica nanoparticles (NPs) with mesoporous shells by a novel selective etching strategy. The mechanism of selective etching based on fluoride‐silica chemistry is investigated in detail and thus provides a fundamentally novel principle for the fabrication of yolk‐shell NPs. Specifically, this unprecedented and versatile synthesis strategy can be used to encapsulate essentially any silica‐based, carbon‐based, metal, metal oxide, or other possible NPs. Noteworthy is that most of the yolk‐shell mesoporous silica (mSiO2) NPs are prepared for the first time. To demonstrate the major structural and compositional advantages of the designed yolk‐shell NPs, their applications in the fields of ultralow‐dielectric constant (k) materials, drug delivery systems, and catalysts were explored. In detail, the lowest k value of the prepared yolk‐shellordered mesoporous silica@mSiO2/fluorinated polybenzoxazole composite films is 2.02; The obtained yolk‐shell mSiO2/C@mSiO2/C NPs possess high hydrophilicity and pH‐responsive sensitivity; The conversion of the catalytic reaction of the designed magnetic yolk‐shell hollow Fe3O4@SiO2/Au@mSiO2 NPs at 20 min is 97% with a high conversion rate (92%) and recyclability even after 10 reuses. This innovative work lays a solid foundation for freely tailorable yolk‐shell encapsulation and will greatly stimulate more efforts devoted to relevant research and development. [ABSTRACT FROM AUTHOR]

Herein, a concise method for the Rh(III)-catalyzed, directing-group-assisted C–H/C–H cross-coupling of N-heterocycles (quinolines, indolines, indoles, pyridines, pyrimidines, pyrazoles) with other heteroarenes (benzoxazoles, benzofurans, and thiophenes) is disclosed for the synthesis of unsymmetrical heterobiaryl compounds in good to excellent yields. A plausible catalytic cycle has been delineated based on experimental and computational mechanistic studies. [ABSTRACT FROM AUTHOR]

Positive-tone photosensitive poly(o-hydroxyamide) (PHA) precursors were synthesized from the polycondensation reaction of 2,2-bis(3-amino-4-hydroxyphenyl)hexafluoropropane (Bis-AP-AF), 4,4'-oxybisbenzoyl chloride (OBC) and three mono-functional amines as end-cappers. The synthesized PHA precursors were characterized and converted to polybenzoxazoles (PBOs) by thermal cyclization reaction. The photoresist formulations composed of the prepared PHA precursor and diazonaphthoquinone (DNQ) photoactive compound were prepared, and the photolithographic properties of the photoresist formulations were investigated by UV light irradiation, followed by a 2.38 wt.% tetramethylammonium hydroxide (TMAH) solution treatment in terms of the chemical structure of end-cappers. The dissolution rate at 2.38 wt.% TMAH solution by various UV light exposure doses and the shrinkage ratio by thermal cyclization of micro-patterns by UV light irradiation and developing process from the photoresist formulations are affected by the chemical structure of end-cappers. [ABSTRACT FROM AUTHOR]

The strategy of modifying phosphane ligands through substituent variation has been widely applied in coordination chemistry and catalysis. This contribution focuses on unsymmetric ferrocene diphosphanes with electronically distinct phosphane moieties, Ph2PfcCH2PAr2 (Ar=Ph, 1; 3,5‐C6H3Me2, 2; and 3,5‐C6H3(CF3)2, 3; fc=ferrocene‐1,1′‐diyl), which were synthesized and converted to the corresponding selenides (1Se–3Se) and Pd(0) complexes [Pd(L‐κ2P,P′)(η2‐ma)] (5–8 for L=1–3 and dppf, ma=maleic anhydride). All compounds were characterized by NMR spectroscopy, ESI MS and elemental analysis, and the structures of 2, 1Se ⋅ CHCl3, 2Se and 5 ⋅ PhMe were determined by X‐ray diffraction analysis. In addition, the redox behavior of 1–3 and 5–8 was studied by cyclic voltammetry and rationalized through DFT calculations. The prepared Pd(0) complexes and their model compound [Pd(dppf‐κ2P,P′)(η2‐ma)] were employed in Pd‐catalyzed C−H arylation of benzoxazole with chlorobenzene in n‐butanol in the presence of K3PO4 as the base, and the catalytic results were compared with the collected characterization data, including the 1JPSe coupling constants determined for 1Se–3Se, as a measure of ligand basicity. [ABSTRACT FROM AUTHOR]

A series of soluble thermosetting polyimide resins containing benzoxazole structure were synthesized by two-step polymerization using 4-phenylethynylphthalic anhydride (4-PEPA) as the end-capping reagent, 2-(4-aminophenyl)-5-aminobenzoxazole (BOA) and 3,4′-diaminodiphenyl ether (3,4′-ODA) as the aromatic diamines, and 4,4′-(hexafluoroisopropylidene) diphthalic anhydride (6FDA) as the aromatic dianhydride. The imide oligomers were characterized by employing Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), solubility tests and rheological measurements. Thermosetting polyimides derived from the imide oligomers were then produced via a thermal cross-linking reaction of the phenylethynyl group. The thermal and mechanical properties of the thermosets were studied using thermogravimetric analysis (TGA), dynamic mechanical thermal analysis (DMA), and mechanical property measurements. The effects of chemical architectures and molecular weights of the imide oligomers on processability, thermostability and mechanical properties were systematically investigated. The results showed that all the copolymerized imide oligomers possessed good solubility in organic and low melt viscosity, and the corresponding thermosets exhibited high glass transition temperature (up to 401°C) and 5% weight-loss temperature (up to 533°C) in an air atmosphere while excellent mechanical properties (flexural strength up to 217 MPa and elongation at break up to 11.2%). With the increase of the concentration of the benzoxazole group, the imide oligomers of PI-X-2 (-O-, -BO-, -B-) exhibited less solubility and higher minimum melt viscosity but improved glass transition temperature after curing and mechanical properties of their thermosets. [ABSTRACT FROM AUTHOR]

The efficient and facile preparation of benzoxazole compounds is of great importance, as benzoxazole is an important structural unit in many biologically active natural products and pharmaceutical compounds. Herein, we report carboxyl functionalized FDU-type mesoporous polymers (COOH-MPs), prepared via the evaporation-induced self-assembly method, for the preparation of benzoxazoles through the cyclization of CO2 with 2-aminophenol. The developed COOH-MPs were systematically characterized using small angle XRD, N2 adsorption–desorption, scanning electron microscopy and transmission electron microscopy, Fourier transform infrared spectroscopy, 13C nuclear magnetic resonance and thermo-gravimetric analysis. This COOH-MP material exhibited high surface area, uniform pore size distribution and high thermal stability, showing excellent catalytic performance and reusability in the cyclization of CO2 with 2-aminophenol, without any co-catalyst. [ABSTRACT FROM AUTHOR]

In conclusion, the current Special Issue on indole compounds encompasses many research papers exploring indole derivatives' synthesis, biological activities, and therapeutic potential. In recent years, significant attention has been given to indoles, a diverse group of heterocyclic compounds widely found in nature that play a crucial role in various bioactive natural and synthetic substances [[1]]. A featured review article on indole-containing natural products demonstrated that indole natural products, particularly indole alkaloids, have gained significant attention for their diverse biological activities. [Extracted from the article]

Heterocyclic moieties containing heteroatoms nitrogen, sulfur, and oxygen, such as substituted benzothiazole, have great potential for biological and pharmaceutical importance due to their structural, binding affinity, and photophysical properties. Herein, we have synthesized novel compounds derived from substituted benzothiazole with 2-chloroacetophenone and comparative studies of their mixed ligand metal complexes having 8-hydroxyquinoline. These new compounds were characterized using elemental analysis, magnetic moment determination, molar conductance, melting point determination, and various spectral techniques (FTIR, mass, and 1H NMR spectra). These synthesized compounds were also investigated for their in vitro antimicrobial bioactivity against two bacterial strains; one is gram-positive bacteria Staphylococcus aureus and the second is gram-negative bacteria E. coli and one fungal strain Aspergillus niger using agar well diffusion method and MIC (minimum inhibition concentration) were used to express their antimicrobial activity. Obtained results were compared with Ciprofloxacin and Ketoconazole. Metal complexes possess higher biological activity as compared to free Schiff base ligands in most cases. [ABSTRACT FROM AUTHOR]

Benzoxazole and benzothiazole have a broad spectrum of agricultural biological activities, such as antibacterial, antiviral, and herbicidal activities, which are important fused heterocyclic scaffold structures in agrochemical discovery. In recent years, great progress has been made in the research of benzoxazoles and benzothiazoles, especially in the development of herbicides and insecticides. With the widespread use of benzoxazoles and benzothiazoles, there may be more new products containing benzoxazoles and benzothiazoles in the future. We systematically reviewed the application of benzoxazoles and benzothiazoles in discovering new agrochemicals in the past two decades and summarized the antibacterial, fungicidal, antiviral, herbicidal, and insecticidal activities of the active compounds. We also discussed the structural–activity relationship and mechanism of the active compounds. This work aims to provide inspiration and ideas for the discovery of new agrochemicals based on benzoxazole and benzothiazole. [ABSTRACT FROM AUTHOR]

Moisture detection through naked eye is important in various fields, including pharmaceuticals, fuels, materials, and agriculture. In this study, we demonstrate the use of a strategically designed organic molecule, 2AMBP, for the detection of moisture in organic solvents and real‐life samples. The principle behind this sensory system involves fluoride‐induced deprotonation followed by water‐induced re‐protonation. The deprotonated form of 2AMBP displays a color‐changing response (yellow to pink) even in trace amounts of water (LOD: 0.0207 % by spectrophotometric analysis), making it a highly sensitive probe for detecting moisture. We show that the anionic receptor moieties of 2AMBP can be employed for the quantification of water impurity in various real‐life samples, and we develop inexpensive, reusable, dye‐coated paper sensor for quick onsite moisture detection and quantification. Interestingly, a smart phone camera can be used to provide relative RGB values that directly correlate to the amount of moisture present in the sample. The 2AMBP‐F‐ exhibits significant changes in fluorescence properties in the presence and absence of water, which makes it an effective fluorescent switch for detecting moisture. Overall, 2AMBP is a highly sensitive, sustainable material that can be conveniently used by laymen for moisture detection without the need for specific instruments or expertise. [ABSTRACT FROM AUTHOR]

Novel Pd(II) pincer complexes (1–8) bearing the O,N,N-chelating ligand scaffold with different substituents on the phenyl ring (–H (HL1), –Me (HL2), –OMe (HL3), –tBu (HL4), –F (HL5), –Cl (HL6), –Br (HL7), and –I (HL8)) were synthesized and characterized by 1H NMR, FT-IR, HRMS, and single crystal X-ray diffraction techniques. The molecular structures of complexes 1–3, and 5 demonstrated a distorted square planar geometry comprising two six-membered metallocyclic rings. According to the DNA/BSA binding study, which was performed using UV-visible and fluorescence spectroscopy techniques, the Schiff base ligands and their corresponding Pd(II) complexes possess strong binding affinity to DNA and BSA. The interaction between the complexes and the biomolecules was studied by molecular docking. Moreover, anticancer activities of the ligands and complexes against three human cancer cell lines (A549, HepG2, and T47D) were determined. The results indicate that complex 3 ([Pd(L3)Cl]) could significantly inhibit HepG2 cell proliferation and migration through the induction of apoptosis, intracellular ROS production, and S phase cell cycle arrest. Meanwhile, complex 5 ([Pd(L5)Cl]) showed the highest antiproliferative effect against T47D cancer cells with higher potency than cisplatin. Interestingly, both complexes 3 and 5 are less toxic to normal lung cells (IMR-90), as compared to the cancer cells, suggesting a promising model for novel anticancer drug development. [ABSTRACT FROM AUTHOR]

Cancer is a broad word for a set of diseases that can begin in virtually any organ or tissue of the body and spread to other organs. In 2020, cancer was the largest cause of death worldwide, accounting for 10 million fatalities, or one in every six deaths. Nitrogen containing heterocyclic compounds are a massive research focus because it has a unique position and is a cherished source of a wide range of bioactive molecules in medicinal chemistry. Over 75% of the currently accessible market is covered by FDA‐approved drugs containing nitrogen moieties. DNA topoisomerase II is a reassuring approach for novel anticancer heterocyclic medicines because it plays a crucial role in DNA metabolism, replication, recombination, and repair. Given the importance of topo II in chemotherapy, there is a pressing necessity to boost topo II or multi‐target topo II inhibitors in order to combat drug resistance and minimize toxicity. Following the trend of researching the advancement of effective topo II inhibitors with minimal toxicity, the current review article consolidates a detailed account of nitrogen‐containing heterocyclic compounds and categorizes them into different classes based on structural characterization, such pyrimidine, triazine, pyridine, quinazoline, fluoroquinolones, quinones, pyrazoles, quinoline, carbazoles, β‐carboline, quinolone, naphthalimide, acridone, benzoxazole, pyridophenoxazine, pyrrole, piperazine and imidazole, along with their structure activity relationship, mechanistic aspects, and docking studies (wherever appropriate) were explored. We are certain that the current review paper will help future medical researchers investigate prospective topoisomerase inhibitors as anticancer medicines in a variety of clinical settings. [ABSTRACT FROM AUTHOR]

Based on the interaction with PDB protein 1PXX of the cox-2 enzyme, a novel series of substituted thiazolidinones (TZD 5a-s) and azetidinones (AZT 6a-s) was designed and synthesized. Molecules were synthesized from 2-mercapto benzoxazole (1) using both conventional and microwave irradiation methods, and their in-vitro antioxidant activity was evaluated using the DPPH free radical scavenging activity, as well as their in-vivo anti-inflammatory activity using the carrageenin-induced rat paw edema method. The reaction time, yield, and purity of microwave and conventionally produced molecules are compared in this work. The molecule ethyl 2-(benzoxazol-2-ylthio)acetate (2) is obtained by reacting 2-mercapto benzoxazole (1) with ethyl 2-chloroacetate in the presence of potassium carbonate and dry acetone. The molecule 2-(benzoxazol-2-ylthio)acetohydrazide (3) was synthesized by reacting ethyl 2-(benzoxazol-2-ylthio)acetate (2) with hydrazine hydrate in the presence of absolute alcohol. Compound 2-(benzoxazol-2-ylthio)acetohydrazide (3) on reacting with different aromatic and heterocyclic aldehyde derivative forms 2-(benzoxazol-2-ylthio)-N'-substituted acetohydrazide Schiff bases (4a-s). 2-(benzoxazol-2-ylthio)-N-(4-oxo-2-substituted thiazolidin-3-yl)acetamide (5a-s) i.e. thiazolidinones benzoxazole derivatives obtained on reacting Schiff bases (4a-s) with thioglycolic acid in a dioxane medium and anhydrous zinc chloride. The Schiff bases (4a-s) were converted into 2-(Benzo[d]oxazol-2-ylthio)-N-(3-chloro-2-oxo-4-substituted azetidin-1-yl)acetamide (6a-s) after treatment with chloroacetyl chloride in the presence of triethanol amine and dioxane. This study focuses on screening of novel synthesized benzoxazole derivatives for in vitro antioxidant, in vivo anti-inflammatory activity, and the evaluation of ulcerogenic activity. The in vivo activity is correlated with the in silico activity, the 3 D QSAR studies were performed for all the compounds by using computer program i.e. SYBYL-X 2.1.1 software. The best CoMFA and CoMSIA models were obtained for the training set compounds with 0.753 and 0.646 leave-one-out coefficients (q2), 0.714 and 0.619 cross validated correlation coefficients (r2cv), and 0.975 and 0.983 conventional coefficients (r2), respectively. Both models were validated with a test set of eight compounds, giving the CoMFA and CoMSIA models a satisfactory prediction (r2pred) of 0.788 and 0.663, respectively. The findings of the study would provide valuable information for the design of new compounds and would also help in predicting the activity of designed compounds. To identify the lead molecule docking studies are performed on COX-2 enzyme of protein 1PXX, the molecules 5c, 5q, 5j, 6q, and 6 g derivatives obtained good - c-docker interaction energy respectively, and in vivo acute ulcerogenic activity. [ABSTRACT FROM AUTHOR]

Tetrasubstituted imidazoles containing a benzothiazole moiety can be formed by a one-pot three-component synthesis from aldehydes, benzil, and 1,3-benzothiazol-2-amine. The synthesized compounds (1–4) are characterized by Fourier-transform infrared spectroscopy (FT-IR), nuclear magnetic resonance spectroscopy (13C, 1H NMR), and mass spectra. The derivatives (1–4) were predicted as anti-breast cancer by docking and DFT study utilization. Discovery Studio Visualizer (DSV) and MGL (Molecular Graphic Laboratory) performed the Autodock procedure. Molecules' adsorption sites were revealed by measuring the total electron density (TED). Furthermore, variables were utilized to determine which of the molecules were more efficient than the others. The binding energy (Eb) of organic compounds was employed in docking simulations to investigate the inhibitory ability. DFT and docking revealed that 1, 2, and 3 were the most effective inhibitory positions. [ABSTRACT FROM AUTHOR]

Adsorption on activated carbons (AC) is a reliable method for extracting aromatic synthetic organic substances from water. The nature of substituents (acceptor or donor groups) and their number in the benzene ring change the strength of interaction with water molecules and the strength of the π–π interaction between the benzene rings of the molecules of the adsorbate and the basal layer of activated carbons, respectively, determining the selectivity of adsorption of organic substances. The purpose of this work is to determine the effect of substituents in the benzene ring on the efficiency of the adsorption of aromatic compounds on activated carbons. The paper considers the isothermal adsorption of nine monoaromatic compounds of the phenolic and aniline series from an aqueous solution on KAU activated carbon produced by high-temperature activation of fruit pits. The efficiency of selective adsorption was estimated based on the Gibbs adsorption energy and adsorption values in the initial section of the isotherms. The efficiency of adsorption of the studied aromatic substances on KAU activated carbon within equilibrium concentrations close to the conventional conditions of the extraction process is completely determined by the value of ∆Gа and increases in the series of phenol < aniline < o-chlorophenol < o-aminophenol < o-aminobenzoic acid < dinitrophenol < o-nitrophenol < p-nitroaniline. Changes in the adsorption energy are considered taking into account the surface charge and charged particles of structural units of aromatic molecules formed under the effect of solution pH. The adsorbate with two donor groups, o-aminophenol, had no advantages in adsorption energy over adsorbates with acceptor and donor substituents. A linear correlation is revealed between the rise of adsorption energy and the decrease in solubility of aniline and phenol derivatives. The effect of the substituent on the efficiency of the adsorption interaction is thus reduced to a dominant effect on the hydration energy of the aromatic compound. [ABSTRACT FROM AUTHOR]

Secondary bile acids promote gastrointestinal (GI) tract permeabilization both in vivo and in vitro. Consumption of high fat diets increases bile acid levels in the GI tract which can contribute to intestinal permeabilization and consequent local and systemic inflammation. This work investigated the mechanisms involved in bile acid (deoxycholic acid (DCA))-induced intestinal epithelial cell monolayer permeabilization and the preventive capacity of (-)-epicatechin (EC). While EC prevented high fat diet-induced intestinal permeabilization in mice, it did not mitigate the associated increase in fecal/cecal total and individual bile acids. In vitro, using differentiated Caco-2 cells as a model of epithelial barrier, EC and other NADPH oxidase inhibitors (VAS-2870 and apocynin) mitigated DCA-induced Caco-2 monolayer permeabilization. While EC inhibited DCA-mediated increase in cell oxidants, it did not prevent DCA-induced mitochondrial oxidant production. Prevention of DCA-induced ERK1/2 activation with EC, VAS-2870, apocynin and the MEK inhibitor U0126, also prevented monolayer permeabilization, stressing the key involvement of ERK1/2 in this process and its redox regulation. Downstream, DCA promoted myosin light chain (MLC) phosphorylation which was related to MLC phosphatase (MLCP) inhibition by ERK1/2. DCA also decreased the levels of the tight junction proteins ZO-1 and occludin, which can be related to MMP-2 activation and consequent ZO-1 and occludin degradation. Both events were prevented by EC, NADPH oxidase and ERK1/2 inhibitors. Thus, DCA-induced Caco-2 monolayer permeabilization occurs mainly secondary to a redox-regulated ERK1/2 activation and downstream disruption of TJ structure and dynamic. EC's capacity to mitigate in vivo the gastrointestinal permeabilization caused by consumption of high-fat diets can be in part related to its capacity to inhibit bile-induced NADPH oxidase and ERK1/2 activation.

In the reaction of 3-aminothymoquinone and aromatic aldehydes, two benzoxazole derivatives viz. 2-(4-methoxyphenyl)-4-methyl-7-isopropyl-1,3-benzoxazol-5-ol (1) and 2-(4- trifluoromethyl)-4-methyl 7-isopropyl-1,3-benzoxazol-5-ol (2) were prepared and characterized by elemental analysis, infrared and 1 H, and 13C-nuclear magnetic resonance spectroscopy and mass spectrometry. Their antimicrobial activity against Escherichia coli, Salmonella enterica, Proteus hauseri, Pseudomonas aeruginosa, Staphylococcus aureus, Sarcina lutea, Clostridium sporogenes and Bacillus subtilis was tested. Synthesized compounds show the best activity on Sarcina lutea, and the lowest against Proteus hauseri and Clostridium sporogenes. The paper assesses in silico methods of the possible ways selected derivatives bind to the enzyme deoxyribonucleic acid gyrase (1KZN). The docking results were compared with those obtained from in vitro antimicrobial activity. Molecular properties and absorption, distribution, metabolism and excretion parameters were also calculated for compounds. The difference in the obtained values reflects differences in the derivatives structures. In the future, tests on a number of enzymes crucial for bacterial life as well as a number of derivatives may offer further information on the mechanisms of action of these substances. [ABSTRACT FROM AUTHOR]

The excellent photocatalytic hydrogenation of 4‐nitrophenol (4‐NP) to 4‐aminophenol (4‐AP) with NaBH4 in the aqueous medium is still a big challenge. Herein, we report a facile one‐pot evaporation‐induced self‐assembly (EISA) method to synthesize a series of CuO/TiO2 nanocomposites. The as‐synthesized CuO/TiO2 photocatalysts exhibit remarkable catalytic activity under direct sunlight in selective hydrogenation of 4‐nitrophenol (4‐NP) to 4‐aminophenol (4‐AP) due to the synergistic interaction of guest copper nanoparticles with host titanium dioxide (TiO2) species. Especially, 5 wt% CuO/TiO2 nanocomposite revealed superior reaction rate constant (k) value (0.306 min−1) when compared to 3 wt% CuO/TiO2 (0.192 min−1) and 7 wt% CuO/TiO2 (0.240 min−1). Moreover, several characterization techniques (XRD, TEM, N2 adsorption–desorption isotherm, DRS, and XPS) were executed to deeply investigate the effect of copper content on the bulk and interfacial properties of the catalysts. The characterization results proved that the superior photocatalytic hydrogenation over 5 wt% CuO/TiO2 catalyst can be ascribed to moderate CuO loading as well as even dispersion of CuO species on the surface of active TiO2 host, which can largely improve the light absorption ability within visible light region. Besides, the 5 wt% CuO/TiO2 catalyst exhibits remarkable recyclability and durability, retaining its superior activity (above 95%) up to several repeating cycles, proving its practical applicability for hydrogenation reactions at domestic and industrial levels. [ABSTRACT FROM AUTHOR]