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The title compound, C9H7NO3, crystallizes in the monoclinic (P21) space group. In the crystal, the almost planar molecules display a flattened herringbone arrangement. Stacking molecules are slipped in the lengthwise and widthwise directions and are linked by C-C interactions [d(Cg...Cg = 3.6640 (11) A ° ]. The structure is characterized by strong C--H...N and weak C--H...O hydrogen bonds, and further stabilized by C-O...C interactions. [ABSTRACT FROM AUTHOR]

We have developed a convenient microwave-assisted synthesis of benzoxazoles starting from nitrophenol and carboxylic acids. The reaction sequence can be performed as a one-pot synthesis comprising an initial reductive transfer hydrogenation of the nitro-group with 1,4-cyclohexadiene and Pd/C followed by subsequent formation of the heteroaromatic moiety with propylphosphonic anhydride (T3P). The method gives facile access to various 2-substituted benzoxazoles in 56–83 % yield.

A series of benzoxazole based 5-(alkoxy)-2-(((4-(5-methylbenzoxazol-2-yl-)- phenyl)imino)methyl)phenol, HLn (n = 10, 12, 14) and their copper(II) complexes had been synthesized; molecular structures of all the organic compounds and the metal complexes were elucidated by various spectroscopic techniques along with elemental analyses. Thermotropic properties were investigated by a combination of POM observation, DSC analysis and X-ray diffraction experiments. All members of the series exhibit enantiotropic smectic-A (SmA) mesophase. DFT calculations imply stable electronic structure of the ligand; HLn (n = 12) as well as of its copper(II) complex.

A series of 12 compounds was designed and synthesized, based on 2-mercaptobenzoxazole derivatives containing either the substituted benzenes 4a–d, substituted isatins 5a–f, or heterocycles 6a–b. The in vitro antiproliferative activity of the compounds was evaluated against hepatocellular carcinoma (HepG2), mammary gland cancer (MCF-7), breast cancer (MDA-MB-231), and the epithelioid cervix carcinoma (HeLa) cancer cell lines. Compounds 4b, 4d, 5d, and 6b had the most potent antiproliferative activity, with IC50 values ranging from 2.14 to 19.34 µM, compared to the reference drugs, doxorubicin and sunitinib. Compound 6b revealed a remarkably broad antitumor activity pattern against HepG2 (IC50 6.83 µM), MCF-7 (IC50 3.64 µM), MDA-MB-231 (IC50 2.14 µM), and HeLa (IC50 5.18 µM). In addition, compound 6b showed potent inhibitory activities against EGFR, HER2, VEGFR2, and the CDK2 protein kinase enzymes, with IC50 values of 0.279, 0.224, 0.565, and 0.886 µM, respectively. Moreover, compound 6b induced caspase-dependent apoptosis and cell cycle arrest at the G2/M phase. Finally, a molecular docking simulation was performed for compound 6b to predict the potential ligand–protein interactions with the active sites of the EGFR, HER2, and VEGFR2 proteins.

Two π-conjugated covalent organic frameworks (COFs) with nonring imine or benzoxazole ring linkages were prepared by reacting 3,3'-dihydrooxybenzidine (BDOH) with 3,5-triformylbenzene (Tb) in the presence or absence of benzimidazole (BDOH-Tb- IM and BDOH-Tb- BO ). Although two COFs indicated similar composition, crystalline structures, and morphologies, imine-based BDOH-Tb- IM exhibited a photocatalytic H 2 O 2 production rate of 2490 μmol·g -1 ·h -1 in sacrificial reagent-free pure water, higher than that of benzoxazole-based BDOH-Tb- BO-a (1168 μmol·g -1 ·h -1 ). The higher photocatalytic activity of BDOH-Tb- IM was attributed to its more efficient photoinduced charge separation and utilization efficiency and different 2e - ORR active sites over the two COFs. This study demonstrated an available ring effect to adjust photocatalytic performance between π-conjugated COFs.

Benzoxazole and naphthoxazole fused systems are found in many biologically active molecules. Novel benzoxazole and naphthoxazole analogs functionalized by the 2,4-dihydroxyphenyl moiety were designed, obtained and evaluated as a broad spectrum of biological potency compounds. Sulfinylbis[(2,4-dihydroxyphenyl)methanethione] or its analogs and 2-aminophenols or 1-amino-2-naphthol were used as starting reagents. 4-(Naphtho[1,2-d][1,3]oxazol-2-yl)benzene-1,3-diol was identified as the most promising compound of the nanomolar activity against AChE (IC50 = 58 nM) of the mixed-type inhibition and of the moderate activity against BChE (IC50 = 981 nM). The higher antiproliferative potency against a panel of human cancer cell lines for naphtho[1,2-d][1,3]oxazoles than for benzoxazoles was found. The activity of the analog with chlorine atom was in the range of 2.18–2.89 µM (IC50) against all studied cells and it is similar to that of cisplatin studied comparatively. Moreover, this compound was not toxic at this concentration to human normal breast cells and keratinocytes. For some compounds it also has proved antioxidant properties at the level of IC50 = 0.214 µM, for the most active compound. The lipophilicity of all compounds, expressed as log p values, is within the range recommended for potential drugs. The biological activity profile of the considered analogs and their lipophilic level justify the search for agents used in AD or in anticancer therapy in this group of compounds.

Benzimidazole and benzoxazole derivatives are included in the category of medical drugs in a wide range of areas such as anticancer, anticoagulant, antihypertensive, anti- inflammatory, antimicrobial, antiparasitic, antiviral, antioxidant, immunomodulators, proton pump inhibitors, hormone modulators, etc. Many researchers have focused on synthesizing more effective benzimidazole and benzoxazole derivatives for screening various biological activities. In addition, there are benzimidazole and benzoxazole rings as bioisosteres of aromatic rings found in drugs used in the treatment of Alzheimer's disease. Because of the diverse activity of the benzimidazole and benzoxazole rings and bioisosteres marketed as drugs for Alzheimer Diseases, designed compounds containing these rings are likely to be effective against Alzheimer's disease. In this study, the effectiveness of compounds containing benzimidazole and benzoxazole rings against Alzheimer's disease will be examined., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

In order to discover more promising anti-fungal agents, a series of benzoxazole family was synthesized by PPA-catalyzed condensation and a Raney nickel/hydrazine reduction. Altogether 45 compounds were obtained in good to excellent yields and characterized by FT-IR, NMR, MS, and X-ray crystal diffraction. Moreover, the biological activity against eight phytopathogenic fungi was investigated. All in all, most of these compounds bear moderate antifungal activities. Among them, three candidates show the strongest activities, compound 4ac, 4bc provided over 50% inhibition rate against five fungi. Especially, the inhibitory rate of compound 4ah on Mycosphaerella melonis reached 76.4%.

Microwave irradiation has been used to enhance the reaction yields and selectivities for organic transformation. In this paper, microwave irradiation (MW) was investigated for the environmentally benign synthesis of benzoxazoles through the cyclization of 2-aminophenols and benzaldehydes using deep eutectic solvent (DES) as a catalyst. The [CholineCl][oxalic acid] was easily synthesized from choline chloride with oxalic acid and used without further purification. [CholineCl][oxalic acid] catalyzed the synthesis of benzoxazoles to produce the desired product in a good to excellent conversion and selectivity under MW irradiation. The presence of [CholineCl][oxalic acid] helps to promote the rapid heating transfer from microwave irradiation into the reaction mixture. The [CholineCl][oxalic acid] can be recovered and reused several times without a considerable degradation in catalytic activity.

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]

Benzoxazolyl linked meta- and para-substituted new chemical entities (5a–5h) featuring thiazolidinedione, rhodanine, hydantoin, and thiohydantoin moieties were synthesized and characterized by 1H NMR, 13C NMR, FT-IR, and HRMS spectral studies. In addition, all compounds were screened for α-glucosidase inhibitory activity and further supported by molecular docking studies carried out at the active site of α-glucosidase (PDB code: 3TOP) in comparison to acarbose used as a standard drug. Out of eight tested compounds, 5d was found as the most active inhibitor of α-glucosidase (IC50 = 9.48 ± 0.36 µM), having rhodanine moiety substituted at meta-position of the phenyl ring. [ABSTRACT FROM AUTHOR]

Molecules that exhibit solid-state luminescence enhancement, i.e. the rare property to be more strongly emissive in the solid state than in solution, find an increasing number of applications in the fields of optoelectronic and nanophotonic devices, sensors, security papers, imaging, and theranostics. Benzazole (BZ) heterocycles are of particular value in this context. The simple enlargement of their π-electron system using a –C=C–Ar or –N=C–Ar moiety is enough for intrinsic solid-state luminescence enhancement (SLE) properties to appear. Their association with a variety of polyaromatic motifs leads to SLE-active molecules that frequently display attractive electroluminescent properties and are sensitive to mechanical stimuli. The excited-state intramolecular proton transfer (ESIPT) process that takes place in some hydroxy derivatives reinforces the SLE effect and enables the development of new sensors based on a protection/deprotection strategy. BZ may also be incorporated into frameworks that are prototypical aggregation-induced enhancement (AIE) luminogens, such as the popular tetraphenylethene (TPE), leading to materials with excellent optical and electroluminescent performance. This review encompasses the various ways to use BZ units in SLE systems. It underlines the significant progresses recently made in the understanding of the photophysical mechanisms involved. A brief overview of the synthesis shows that BZ units are robust building blocks, easily incorporated into a variety of structures. Generally speaking, we try to show how these small heterocycles may offer advantages for the design of increasingly efficient luminescent materials. [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]

In this study, the new compound 2-(p-Fluorophenyl)-5-(2-(4-acetylpiperazine-1-yl) acetamido)benzoxazole was synthesized in three steps and its structure was clarified by ¹H-NMR and 13C-NMR spectroscopy. Its antimicrobial activity was studied on Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Acinetobacter baumannii NTCC 13304, Klebsiella pneumoniae ATCC 700603, Candida albicans ATCC 1023, and their isolates. When the antimicrobial activity results were examined, although the reference drugs showed better antimicrobial activity in general, the synthesized compound showed quite promising activity on E. faecalis isolates and E. coli isolates compared to ampicillin with MIC: 32 µg mL-1. Molecular docking study was carried out on the DNA gyrase subunit B structure. Theoretical ADME (absorption, distribution, metabolism, elimination) properties were calculated. In addition, HOMO-LUMO energies, molecular electrostatic potential analysis, and optimized geometric structure were determined using the DFT/B3LYP method and the 6-311G (d,p) basis set, and the results were displayed. [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]

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]

Spectroscopic, DFT, and SERS studies of antimicrobial bioactive 2-(p-bromophenyl)-5-(2-(4-(p-chlorophenyl)piperazine-1-yl)acetamido)benzoxazole (BCAB) have been reported. Very large changes are seen wavenumbers in Raman and SERS. Variations in modes may be due to surface π-electron interactions and means, the BACB is inclined with respect to the metal surface. Theoretical molecular geometry optimization parameters, wavenumbers, frontier molecular orbitals, and molecular electrostatic potential surface have been calculated using density functional theory. The docked ligand forms a stable complex with SOCS-2 and can be BCAB may be an anti-cancerous drug. According to RMSD, RMSF, and Rg analysis, BACB and SOCS-2 protein form a stable and stable interaction. [ABSTRACT FROM AUTHOR]

Twenty-four analogs based on triazinoindole bearing benzimidazole/benzoxazole moieties (1–25) were synthesized. Utilizing a variety of spectroscopic methods, including 1H-, 13C-NMR, and HREI-MS, the newly afforded compounds (1–25) were analyzed. The synthesized analogs were tested against urease enzyme (in vitro) as compared to the standard thiourea drug. All triazinoindole-based benzimidazole/benzoxazole analogs (1–25) exhibited moderate to excellent inhibition profiles, having IC50 values of 0.20 ± 0.01 to 36.20 ± 0.70 μM when evaluated under the positive control of thiourea as a standard drug. To better understand the structure–activity relationship, the synthesized compounds were split into two groups, “A” and “B.” Among category “A” analogs, analogs 8 (bearing tri-hydroxy substitutions at the 2,4,6-position of aryl ring C) and 5 (bearing di-hydroxy substitutions at the 3,4-position of aryl ring C) emerged as the most potent inhibitors of urease enzyme and displayed many times more potency than a standard thiourea drug. Besides that, analog 22 (which holds di-hydroxy substitutions at the 2,3-position of the aryl ring) and analog 23 (bearing ortho-fluoro substitution) showed ten-fold-enhanced inhibitory potential compared to standard thiourea among category “B” analogs. Molecular docking studies on the active analogs of each category were performed; the results obtained revealed that the presence of hydroxy and fluoro-substitutions on different positions of aryl ring C play a pivotal role in binding interactions with the active site of the targeted urease enzyme.

This work is one of our efforts to discover potent anticancer agents. We modified the most promising derivative of our previous work concerned with the development of VEGFR-2 inhibitor candidates. Thirteen new compounds based on benzoxazole moiety were synthesized and evaluated against three human cancer cell lines, namely, breast cancer (MCF-7), colorectal carcinoma (HCT116), and hepatocellular carcinoma (HepG2). The synthesized compounds were also evaluated against VEGFR-2 kinase activity. The biological testing fallouts showed that compound 8d was more potent than standard sorafenib. Such compound showed IC50 values of 3.43, 2.79, and 2.43 µM against the aforementioned cancer cell lines, respectively, compared to IC50 values of 4.21, 5.30, and 3.40 µM reported for sorafenib. Compound 8d also was found to exert exceptional VEGFR-2 inhibition activity with an IC50 value of 0.0554 μM compared to sorafenib (0.0782 μM). In addition, compound 8h revealed excellent cytotoxic effects with IC50 values of 3.53, 2.94, and 2.76 µM against experienced cell lines, respectively. Furthermore, compounds 8a and 8e were found to inhibit VEGFR-2 kinase activity with IC50 values of 0.0579 and 0.0741 μM, exceeding that of sorafenib. Compound 8d showed a significant apoptotic effect and arrested the HepG2 cells at the pre-G1 phase. In addition, it exerted a significant inhibition for TNF-α (90.54%) and of IL-6 (92.19%) compared to dexamethasone (93.15%). The molecular docking studies showed that the binding pattern of the new compounds to VEGFR-2 kinase was similar to that of sorafenib.

The fluorosulfate derivatives of benzoxazole attract attention since benzoxazole-based compounds have a wide range of biological activities, and the ability of the –SO2F group to react with various functional groups makes it possible to synthesize various new derivatives. The new 2-(2-(fluorosulfonyloxy)phenyl)benzoxazole (2) has been synthesized by the SuFEx click reaction in a two-chamber reactor. Compound 2 is the first example of a benzoxazole derivative with a fluorosulfate-containing substituent at position two of the benzoxazole heterocycle. The anti-cancer potency of 2 was evaluated in silico using molecular docking. The docking results suggest that title compound 2 is of great interest for further studies as a possible anaplastic lymphoma kinase inhibitor.

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]

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]

In this study, we report the emissive properties of a heteroleptic cyclometalated Ir(III) complex, [Ir(bzq)2(PBO)] (bzqH = benzo[h]quinoline; PBOH = 2-(2-hydroxyphenyl)benzoxazole). The complex, [Ir(C^N)2(N^O)], was synthesised and optically resolved using a chiral column. Two geometrical isomers, trans-(N,N) and cis-(N,N) isomers, were obtained as the major and minor products in an enantiopure form, respectively. Their molecular structures were determined using single crystal X-ray analysis. In the crystalline states, the intermolecular C–H⋯π interaction between PBO− and an H atom in bzq− was the main factor influencing molecular packing. When the complexes were dissolved in CH2Cl2 and excited at 430 nm under N2 atmosphere, yellow (λmax = 550 nm) and orange emissions (λmax = 570 nm) were observed for the trans-(N,N) and cis-(N,N) isomers, respectively, with the quantum yield higher for the former than the latter. [ABSTRACT FROM AUTHOR]

In this study, we report the synthesis, in silico molecular docking, and in vitro urease inhibition studies of a novel series of benzoxazole derivatives. The title compound in the series namely (2‐(benzo[d]oxazol‐2‐ylthio)‐1‐(4‐substitute‐phenyl)ethan‐1‐one oxime was synthesized by the reaction of 2‐aminophenol with different kinds of intermediates in several steps through both conventional and microwave techniques. All compounds were found to have an excellent degree of urease inhibitory potential ranging from 0.46±0.01 to 46.10±0.45 μM in compared with standard inhibitor acetohydroxamic acid with IC50 320.70±4.24 μM. Structure‐activity relationship was established in detail. In addition, we confirmed the binding interactions of compounds with enzymes using molecular docking. [ABSTRACT FROM AUTHOR]

Novel porphyrin compounds containing benzothiazole, benzoxazole, and benzimidazole moieties have been prepared and their structures have been confirmed. Molecular docking of non-symmetric hetaryl-substituted porphyrins and chlorin e6 with SARS-CoV-2 helicase has been carried out. The affinity of hetaryl-substituted porphyrins to this protein has been found significantly higher than that of the drugs approved by the FDA and chlorin e6. The structure of the complexes of SARS-CoV-2 helicase with the considered macroheterocyclic compounds has been analyzed. Possible ways to inhibit and photoinactivate SARS-CoV helicase have been suggested basing on the localization of porphyrins and chlorin e6 in the helicase domains. [ABSTRACT FROM AUTHOR]

In this study, a new 2.5-substituted benzoxazole derivative compound was synthesized in three steps, its antimicrobial activities were determined by the microdilution method on Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Candida albicans ATCC 10231 and their isolates, and also in silico studies were performed. The structure of the compound was illuminated by 1H-NMR and 13C-NMR spectroscopy and HRMS, and the resulting analysis results proved our structure. When the antimicrobial activity results were examined, although the reference drugs generally showed better antimicrobial activity, it was observed that the synthesized compound showed very promising activity against Candida albicans isolate with MIC: 16 ug/mL. Molecular docking studies were conducted to understand the mechanism of the compound's good antimicrobial effect against Candida albicans isolate (PDB: 5TZ1). Estimated ADME profiles were determined. In addition, quantum chemical calculations were made with the DFT/B3LYP method in the 6-311G (d,p) basic set, the structural properties, geometry, electronic and thermodynamic properties of the molecule were determined and the results were displayed. [ABSTRACT FROM AUTHOR]

A series of methacrylamides containing benzoxazole (BO) mesogenic side groups and different lengths of alkyl units was synthesized in this study. A methacrylamide containing the n‐dodecyl group was selected as a suitable monomer to obtain beneficial thermally conductive polymeric materials because of its sufficient solubility in toluene in the subsequent radical polymerization and because of its liquid crystallinity. This methacrylamide led to a highly soluble polymer with film‐forming ability. The BO‐containing polymethacrylamide also exhibited liquid‐crystalline (LC) behavior during the heating and cooling processes. The cast film was kept at a slightly lower temperature than the clearing temperature and quenched to room temperature. This procedure afforded a film maintaining optical anisotropy at room temperature, implying that a frozen LC structure is maintained at room temperature. The quenched film also resulted in a significantly enhanced thermal conductivity (λ = 0.60 W m−1 K−1) without the aid of fillers and external fields, unlike the as‐cast counterpart without optical anisotropy. A polyacrylate containing a flexible long alkylene (C6) spacer between the main chains and a BO‐containing mesogenic side group was also investigated. The polyacrylate exhibited LC behavior during the heating and cooling processes over wide ranges. The polyacrylate film quenched from an established temperature, which contains a frozen LC structure, also exhibited a significantly enhanced λ value (0.63 W m−1 K−1) without fillers and external fields. Thus, the BO‐containing vinyl polymers studied in this work are promising candidates for novel heat‐releasing materials. © 2020 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

(E)-4-(3,5-Bis(benzo[d]oxazol-2-yl)-2,6-dihydroxystyryl)-1-ethylpyridin-1-ium iodide (3) with extended conjugation was synthesized by coupling a styryl substituent into the bis(HBO) 1 structure. Probe 3 exhibited bright red emission (λem ≈ 600 nm) with a large Stokes shift (Δλ ≈ 210 nm), attributing to strong ICT enhanced by ESIPT. The role of the styryl substituent was further evaluated with the aid of low temperature fluorescence. Probe 3 exhibited excellent selectivity towards fluoride anions in solution by generating a near infrared emission peak at λem ≈ 720 nm. Probe 3 was found to be a useful tool for quantifying fluoride content in solution by both absorbance and emission measurements. The fluoride binding of 3 was assumed to occur via strong intermolecular hydrogen bonding with the F− anion (K = 3413). The association stoichiometry for the 3-F complex was found to be (1 : 1) according to the Benesi-Hildebrand method. [ABSTRACT FROM AUTHOR]

We report a simple oxidative Csp3−H functionalization reaction of glycine derivatives by visible‐light photoredox catalysis. A wide range of glycine derivatives readily undergo the oxidative cyclization to afford various 2‐substituted benzoxazoles. Importantly, this photocatalytic intramolecular dehydrogenative coupling reaction allows for the C−H functionalization of glycine derivatives involving short peptides under mild conditions, which may have value in preparing peptide‐derived pharmacologically active molecules. [ABSTRACT FROM AUTHOR]

• Synthesis and spectroscopic characterization of benzoxazole-based thiazolidinone derivatives. • Isolated compounds were tested for in vitro anti-cholinesterase inhibition. • A number of the compounds demonstrated excellent activity, some better than the reference standards. • A molecular docking study was used to determine the binding interactions of the potent compounds with the enzymes. Benzoxazole-based thiazolidinone hybrids derivatives (1–19) were afforded and further subjected to in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition studies for the first time. All these analogues were found to display good inhibition against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)enzymes with IC 50 values 4.20 ± 1.10 µM to 43.20 ± 4.50 µM (against AChE) and 3.80 ± 1.20 µM to 34.50 ± 3.30 µM (against BuChE) as compared to standard donepezil having IC 50 values of 21.86 ± 0.40 µM (against AChE) and 32.47 ± 2.30 µM (against BuChE) respectively. Specifically, compound 16, characterized by a 3,4-dichloro substitution on ring B and 2–OH and 4-CF3 substitutions on ring C, along with compound 13, having 2,4-diCl on ring B and 2-OH and 4-CF 3 on ring C, were identified as the most potent inhibitors of the targeted AChE and BuChE enzymes, even manifolds more potent than standard donepezil drug. The structures of all synthesized analogues were verified through the utilization of multiple spectroscopic techniques, including HREI-MS and NMR (1H NMR and 13C NMR). The structure-activity relationship (SAR) demonstrated that analogs bearing electron withdrawing groups such as –CF 3 , –Cl and -NO 2 groups displayed superior AChE and BuChE activities. In the molecular docking analysis of the most potent analogs, a favorable protein-ligand interaction (PLI) profile was observed with the respective targets (AChE and BuChE). These interactions encompassed crucial bonding types such as hydrogen bonding, π-π interactions, π-π stacking, and hydrophobic interactions. [ABSTRACT FROM AUTHOR]

• Focused on the bifunctional receptor for the detection of cations and anions. • The calixarene was characterised using 1H, 13C, FT-IR and UV–vis data. • Receptor showed high selectivity and sensitivity for CH 3 COO−, CN−, F − and Cu2+ ions. We have synthesized and evaluated a calix[4]arene-based bifunctional receptor containing amide and benzoxazolinone units for ionic recognition. Absorption properties of this receptor have been studied, and the results revealed selectivity in the recognition of copper (Cu2+), fluoride (F −), cyanide (CN−), and acetate (CH 3 COO−) ions. Its binding ability and the mechanism as bifunctional receptor were elucidated using advanced techniques such as 1HNMR and FT-IR analysis. The results showed that receptor amide bridge played a critical role in the binding of copper (II), acetate, cyanide, and fluoride ions. These findings suggest that calix[4]arene-based bifunctional receptor has promising potential as an ion sensor for detecting these specific ions in environmental and biological samples. This research contributes to the ongoing exploration of bifunctional receptors and their potential applications in the field of supramolecular chemistry. [ABSTRACT FROM AUTHOR]

A facile and effective C–H functionalization strategy for the synthesis of 2-mercaptobenzothiazoles and 2-mercaptobenzoxazoles is described. 1,3-Propanedithiol was employed to convert benzothiazoles and benzoxazoles to the corresponding heteroarylthiols in the presence of potassium hydroxide and DMSO. This novel protocol is featured by direct C–H mercaptalization of heteroarenes and a simple reaction system.

LPS induces inflammatory cytokines, including IL-1β, IL-6, and TNF-α, and causes an inflammatory response. The development of small molecules that have suppressive effect on those inflammatory cytokines is a desirable strategy for the treatment of inflammatory diseases. We synthesized 12 novel compounds with 4-amino-N-(4-(benzo[d]oxazol-2-ylamino)phenyl)butanamide moiety and evaluated their biological activities. Among them, 4 compounds (compound 5d, 5c, 5f, 5m and synthetic intermediate 4d) showed potent inhibition activities on IL-1β and IL-6 mRNA expression in vitro. Further, in vivo activity was evaluated with two compounds (5f and 4d) and mRNA levels of IL-1β, IL-6, and TNF-α were significantly decreased without hepatotoxicity. From the in vivo and in vitro test results, we confirmed that our synthesized compounds are effective for suppression of representative inflammatory cytokines.

In this work simple efficient, one pot and environmentally friendly method was developed for the synthesis of 2-Aryl-1H-benzoxazole derivatives at 80o C using ortho-aminophenol and various aldehydes. It has been found that Dowex 50W is an effective catalyst to prepare moderate to high yield of a variety of benzoxazole derivatives through a clean and simple process. Aqueous medium, green methodology, rapid reaction, reusability of heterogeneous catalyst are the great advantages of this protocol. [ABSTRACT FROM AUTHOR]

In this study, Mitsunobu reagent, DEAD (diethyl azodicarboxylate) and PPh3, and ethyl‐oxalamide derivatives of 2‐aminophenol were reacted under mild reaction conditions. As a result of the cyclization reaction, benzoxazole derivatives bearing an ester group in the C‐2 position were obtained in a one‐pot protocol. It was observed that the electron‐donating groups at the C‐5 position and the electron‐withdrawing groups at the C‐6 position of the benzene ring increased the yield of the cyclic product. It was found that the cyclization does not occur when the carboxylic acid group is substituted in the benzene ring. The cyclization reaction we performed preferred the 5‐endo‐trig reaction instead of the 6‐exo‐trig. This experimental result was examined in detail with density functional theory (DFT) calculations as well. A computational exploration is presented herein that elucidates the detailed mechanism for Huisgen zwitterion's reaction with ethyl‐oxalamide derivatives of 2‐aminophenol. Potential alternative mechanisms were modeled with DFT calculations via CPCM/M06‐2X/6‐311++G(d,p)//B3LYP/6‐31+G(d,p) level method in tetrahydrofuran to understand shed light on the mechanism. Our computational results are in good agreement with experimental findings that benzoxazole derivatives are the sole products in this reaction. [ABSTRACT FROM AUTHOR]

Background. Benzoxazole derivatives have different biological activities. In pursuit of designing novel chemical entities with antiprotozoal and antimicrobial activities, benzoxazolyl aniline was utilized as a privileged scaffold of a series of (3-benzoxazole-2-yl) phenylamine derivatives, 3-benzoxazoloyl acetamide, and butyramide derivatives. Methods. These novel analogs were synthesized in straightforward simple chemistry without any quantitative chromatographic separations in reasonable yields. The biological evaluation of all target compounds as potential antimalarial, antileishmanial, antitrypanosomal, and antimicrobial agents was performed by various well-established cell-based methods. Results. Compounds 6d and 5a showed promising biological screening data. The amidation of 3-benzoxazolyl aniline 1 with the chloroacetyl functional group resulted in a good antimalarial activity and showed moderate inhibitory activities against leishmanial and trypanosomal spp. Moreover, chloroacetyl functionalization of benzoxazolyl aniline serves as a good early goal for constructing and synthesizing new antimicrobial and antiprotozoal agents. The molecular docking study rationalizes the relative inhibitory activity of compound 5a as an antimalarial agent with the deregulation of PfPNP activity which has emerged as a major mechanism of these targets. [ABSTRACT FROM AUTHOR]

The palladium complex of dendronized amine polymer (EG–Gn–Pd, n = 0, 1 and 2) having ethylene glycol‐initiated polyepichlorohydrin as core was synthesized on a Merrifield resin support and was well characterized. Generally, palladium catalysts are known for carbon–carbon coupling reactions. Here, a developed catalyst was found to be good for benzoxazole synthesis. Higher generation dendronized polymer (EG–G2–Pd) was found to be better catalyst over lower generation dendronized polymers. Moreover, dendronized polymers were found to be a better catalyst over dendrigraft polymers. The catalyst reusability was checked and good yield was obtained for five cycles. [ABSTRACT FROM AUTHOR]

Using X-ray single crystal diffraction, the crystal structures of biologically active benzoxazole derivatives were determined. DFT calculation was performed with standard 6-31G*(d), 6-31G** and 6-31+G* basis set to analyze the molecular geometry and compare with experimentally obtained X-ray crystal data of compounds. The calculated HOMO-LUMO energy gap in compound 2 (2-(2-hydroxynaphtalen-1-yl)-4-methyl-7-isopropyl-1,3-benzoxazol- 5-ol) is 3.80 eV and this small gap value indicates that compound 2 is chemically more reactive compared to compounds 1 (4-methyl-2-phenyl-7-isopropyl-1,3-benzoxazol-5-ol) and 3 (2-(4-chlorophenyl)-4-methyl-7-isopropyl- 1,3-benzoxazol-5-ol). The crystal structures are stabilized by both intra- and intermolecular hydrogen bonds in which an intermolecular O-H⋯N hydrogen bond generates N3 and O7 chain motif in compounds 1, 2, and 3, respectively. The calculated bond lengths and bond angles of all three compounds are remarkably close to the experimental values obtained by X-ray single crystal diffraction. [ABSTRACT FROM AUTHOR]

Eight QSAR models (M1-M8) were developed from a dataset of 118 benzo-fused heteronuclear derivatives targeting VEGFR-2 by Monte Carlo optimization method of CORALSEA 2023 software. Models were generated with hybrid optimal descriptors using both SMILES and Graphs with zero- and first-order Morgan extended connectivity index from a training set of 103 derivatives. All statistical parameters for model validation were within the prescribed limits, establishing the models to be robust and of excellent quality. Among all models, split-2 of M5 was the best-fit as reflected by   r v a lidation 2 ,   Q v a lidation 2 and MAE . Mechanistic interpretation of this model assisted the identification of structural descriptors as promoters and hinderers for VEGFR-2 inhibition. These descriptors were utilized to design novel VEGFR-2 inhibitors (YS01-YS07) by bringing modifications in compound MS90 in the dataset. Docking of all designed compounds, MS90 and sorafenib with VEGFR-2 binding site revealed favourable binding interactions. Docking score of YS07 was higher than that of MS90 and sorafenib. Molecular dynamics simulation study revealed sustained interactions of YS07 with key amino acids of VEGFR-2 at a run time of 100 ns. This study concludes the development of a best fit QSAR model which can assist the design of new anticancer agents targeting VEGFR-2.

An important research topic is the discovery of multifunctional compounds targeting different disease-causing components. This research aimed to design and synthesize a series of 2-aryl-6-carboxamide benzoxazole derivatives that inhibit cholinesterases on both the peripheral anionic and catalytic anionic sides. Compounds (7-48) were prepared from 4-amino-3-hydroxybenzoic acid in three steps. The Ellman test, molecular docking with Maestro, and molecular dynamics simulation studies with Desmond were done (Schrodinger, 12.8.117). Compound 36, the most potent compound among the 42 new compounds synthesized, had an inhibitory concentration of IC 50 12.62 nM for AChE and IC 50 25.45 nM for BChE (whereas donepezil was 69.3 nM and 63.0 nM, respectively). Additionally, compound 36 had docking values ​​of - 7.29 kcal/mol for AChE and - 6.71 kcal/mol for BChE (whereas donepezil was - 6.49 kcal/mol and - 5.057 kcal/mol, respectively). Furthermore, molecular dynamics simulations revealed that compound 36 is stable in the active gorges of both AChE (average RMSD: 1.98 Å) and BChE (average RMSD: 2.2 Å) (donepezil had average RMSD: 1.65 Å and 2.7 Å, respectively). The results show that compound 36 is a potent, selective, mixed-type dual inhibitor of both acetylcholinesterase and butyrylcholinesterase. It does this by binding to both the catalytically active and peripheral anionic sites of cholinesterases at the same time. These findings show that target compounds may be useful for establishing the structural basis for new anti-Alzheimer agents., (© 2024. The Author(s).)

An efficient visible light mediated, eosin Y catalyzed direct C-H oxidative amination of benzoxazoles with secondary amines has been developed, which providing a straightforward, green, and environmentally benign access to a wide variety of substituted benzoxazole-2-amines under mild reaction conditions. The biological studies such as drug-likeness and molecular docking are also carried out on the molecule., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Adenylate‐forming enzymes (AFEs) are a mechanistic superfamily of proteins that are involved in many cellular roles. In the biosynthesis of benzoxazole antibiotics, an AFE has been reported to play a key role in the condensation of cyclic molecules. In the biosynthetic gene cluster for the benzoxazole AJI9561, AjiA1 catalyzes the condensation of two 3‐hydroxyanthranilic acid (3‐HAA) molecules using ATP as a co‐substrate. Here, the enzymatic activity of AjiA1 is reported together with a structural analysis of its apo form. The structure of AjiA1 was solved at 2.0 Å resolution and shows a conserved fold with other AFE family members. AjiA1 exhibits activity in the presence of 3‐HAA (Km = 77.86 ± 28.36, kcat = 0.04 ± 0.004) and also with the alternative substrate 3‐hydroxybenzoic acid (3‐HBA; Km = 22.12 ± 31.35, kcat = 0.08 ± 0.005). The structure of AjiA1 in the apo form also reveals crucial conformational changes that occur during the catalytic cycle of this enzyme which have not been described for any other AFE member. Consequently, the results shown here provide insights into this protein family and a new subgroup is proposed for enzymes that are involved in benzoxazole‐ring formation. [ABSTRACT FROM AUTHOR]

Abstract Background A new series of benzoxazole analogues was synthesized and checked for their in vitro antibacterial, antifungal and anticancer activities. Results and discussion The synthesized benzoxazole compounds were confirmed by IR, 1H/13C-NMR, mass and screened for their in vitro antimicrobial activity against Gram-positive bacterium: Bacillus subtilis, four Gram-negative bacteria: Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Salmonella typhi and two fungal strains: Candida albicans and Aspergillus niger using tube dilution technique and minimum inhibitory concentration (MIC) was noted in µM and compared to ofloxacin and fluconazole. Human colorectal carcinoma (HCT116) cancer cell line was used for the determination of in vitro anticancer activity (IC50 value) by Sulforhodamine B assay using 5-fluorouracil as standard drug. Conclusion The performed study indicated that the compounds 1, 10, 13, 16, 19, 20 and 24 had highest antimicrobial activity with MIC values comparable to ofloxacin and fluconazole and compounds 4, 6, 25 and 26 had best anticancer activity in comparison to 5-fluorouracil.

Abstract A novel series of substituted 2-thiohydantoin incorporated with benzoimidazole, pyrazole, triazole and/or benzoxazole moieties has been synthesized using (E)-3-[1-(4-bromophenyl)ethylideneamino]-2-thioxoimidazolidin-4-one 1 as the key starting material. The key material 1 also, reacted with an acetic anhydride, aromatic aldehydes, secondary amines, formaldehyde and triethyl orthoformate to give the corresponding acetyl, chalcone, Mannich bases and ethoxymethylene derivatives, respectively. The structures of the novel compounds were confirmed by spectral data and elemental analysis. The cytotoxic activity of all synthesized compounds was assessed in vitro against human hepatocellular cancer cell line (HePG-2) and breast carcinoma cell line (MCF-7). The bioassay results revealed that compound 14 has the best activity against HePG-2 cell line (IC50 = 2.33 μg/mL), while compound 5 has the best activity against MCF-7 cell line (IC50 = 3.98 μg/mL).