Benzoxazole Derivatives Research Articles

Novel Sulfonylamido Benzoxazole Derivatives: Synthesis, Characterisation, Molecular Docking, DFT, and Antimicrobial Activity Investigations.

In this work, numerous novel 2-(p-ethyl/fluorophenyl)-5-[(p-substitutedphenyl)sulfonylamido]benzoxazole derivatives were designed, synthesized, and structurally characterized using 1H-NMR, 13C-NMR, mass spectroscopy, and elemental analysis approaches. The antimicrobial activity against several Gram (+) bacteria, Gram (-) bacteria, and fungal species was determined using the in vitro microdilution technique. A molecular docking analysis was performed on all produced compounds utilizing the S. aureus gyrase complex with ciprofloxacin and DNA. Two of the most effective compounds against S. aureus, N4 and N9, have binding energies of -8.7 kcal/mol and -8.6 kcal/mol, respectively, and their interactions have been demonstrated in 2D and 3D. Furthermore, utilizing the 6-311G(d,p) base set and DFT/B3LYP theory, MEP analysis, geometric optimization, and molecular reactivity analysis (HOMO-LUMO) of N4 and N9 were performed, and the results were presented. All compounds' theoretical ADMET profiles were computed as well. With all of this knowledge, this study could be a pioneer in the development of novel anti-S. aureus compounds.

Multifunctional elastic benzoxazole derivative crystals for advanced optoelectronic applications

Multifunctional elastic benzoxazole derivative crystals for advanced optoelectronic applications

Parkinson's Disease: Unravelling the Medicinal Perspectives and Recent Developments of Heterocyclic Monoamine Oxidase-B Inhibitors.

Parkinson's disease is a neurodegenerative condition characterized by slow movement (bradykinesia), tremors, and muscle stiffness. These symptoms occur due to the degeneration of dopamine- producing neurons in the substantia nigra region of the brain, leading to reduced dopamine levels. The development of Parkinson's Disease (PD) involves a combination of genetic and environmental factors. PD is associated with abnormal regulation of the monoamine oxidase (MAO) enzyme. Monoamine oxidase inhibitors (MAOIs) are an important class of drugs used to treat PD and other neurological disorders. In the early stages of PD, monotherapy with MAO-B inhibitors has been shown to be both safe and effective. These inhibitors are also commonly used as adjuncts in long-term disease management, as they can improve both motor and non-motor symptoms, reduce "OFF" periods, and potentially slow disease progression. However, current MAO-B inhibitors come with side effects like dizziness, nausea, vomiting, light-headedness, and fainting. Therefore, accelerating the development of new MAO-B inhibitors with fewer side effects is crucial. This review explores natural compounds that may inhibit monoamine oxidase B (MAO-B), focusing on key findings from the past seven years. It highlights the most effective heterocyclic compounds against MAO-B, including thiazolyl hydrazone, pyridoxine-resveratrol, pyridazine, isoxazole, oxadiazole, benzothiazole, benzoxazole, coumarin, caffeine, pyrazoline, piperazine, piperidine, pyrrolidine, and morpholine derivatives. The review covers in vitro, in silico, and in vivo data, along with the structure- activity relationship of these compounds. These findings offer valuable insights for the development of more effective MAO-B inhibitors and advancements in Parkinson's disease research.

Antimicrobial and Antifungal Activities of Osmium Metal Complex with Benzoxazole Derivative

The combination of some Osmium metal ions with an important 2-(1,3-benzoxazole -2-yl - sulfanyl )-N-phenyl acetamide (BSPA) ligand to form coordination compounds is an important area of current research. Less explored biologically important 2-(1,3-benzoxazole -2-yl - sulfanyl )-N-phenyl acetamide ligand is allowed to react with solution of some rare metal perchlorates and attempt has been made to synthesize solid 2-(1,3-benzoxazole -2-yl- sulfanyl )-N-phenyl acetamide complexes. These 2-(1,3-benzoxazole-2-yl-sulfanyl )-N-phenyl acetamide complexes are subjected to antimicrobial activity of these complexes has been evaluated by standard methods and attempts have been made to correlate structural characteristics with properties of these 2-(1,3-benzoxazole -2-yl - sulfanyl )-N-phenyl acetamide complexes.

Unravelling the structure and reactivity of N,O-heterocycles: a multifaceted quantum chemical approach using a benzoxazole derivative as a case study

Unravelling the structure and reactivity of N,O-heterocycles: a multifaceted quantum chemical approach using a benzoxazole derivative as a case study

The Benzoxazole Heterocycle: A Comprehensive Review of the Most Recent Medicinal Chemistry Developments of Antiproliferative, Brain-Penetrant, and Anti-inflammatory Agents.

The benzoxazole is one of the most widely exploited heterocycles in drug discovery. Natural occurring and synthetic benzoxazoles show a broad range of biological activities. Many benzoxazoles are available for treating several diseases, and, to date, a few are in clinical trials. Moreover, an ever-increasing number of benzoxazole derivatives are under investigation in the early drug discovery phase and as potential hit or lead compounds. This perspective is an attempt to thoroughly review the rational design, the structure-activity relationship, and the biological activity of the most notable benzoxazoles developed during the past 5years (period 2019-to date) in cancers, neurological disorders, and inflammation. We also briefly overviewed each target and its role in the disease. The huge amount of work examined suggests the great potential of the scaffold and the high interest of the scientific community in novel biologically active compounds containing the benzoxazole core.

Design, Synthesis, Computational Study, and Antidiabetic Evaluation of Benzoxazole Derivatives

AbstractAlpha‐amylase plays a crucial role in blood glucose levels, and thus, its inhibitor can be used to control diabetes. Thus, in vitro alpha‐amylase inhibitory activities were studied for synthesized benzoxazole compounds. The 2‐amino‐benzoxazoles were prepared by reacting 2‐aminophenol with cyanogen bromide, which was coupled with phenoxy acetic acid derivatives (6 a‐n). The compound 6 h was found to be significantly active with IC50 values of 348.43 μg/mL against alpha‐amylase compared to acarbose (IC50=682.54 μg/mL). The molecular docking and molecular dynamic simulation showed better affinity and stability of 6 h at the binding site of the alpha‐amylase protein. Further, a preliminary bioevalauation and antidiabetic study were done through in vivo using SD rats. The efficacy study showed a significant improvement in glucose levels, total cholesterol, triglyceride, LDL, and HDL levels in the compound 6 h and was found to be a lead antidiabetic agent.

Ultrasound-promoted synthesis of polysubstituted imidazole-linked benzoxazole derivatives and the investigation of their optical properties

A rapid and efficient synthesis of novel hybrid imidazole-benzoxazole derivatives is described under ultrasound irradiation. These reactions were carried out through a cyclization reaction of polysubstituted imidazole-based o-aminophenols and various benzoic acids in polyphosphoric acid. The starting o-amiophenols were synthesized from corresponding o-nitrophenols using Fe powder in EtOH and acetic acid. o-Nitrophenol derivatives were synthesized from related phenols by employing HNO3 in acetic acid. Structures of the newly obtained products were confirmed by spectral and analytical data. The optical properties of the products were investigated via UV–Vis absorption and fluorescent emission spectroscopy in dilute ethanol solution.

Design and synthesis of new benzoxazole derivatives and study of their interactions with a G4 model by UV spectroscopy and in silico methods

In this study, we synthesized novel benzoxazol-2-ylmethyl-(1H-1,2,3-triazol-4-yl)phenyl)-3-aminopropanamides (6a-d) in high yields by means of the Copper-catalysed Azide-Alkyne Cycloaddition (CuAAC) reaction. The synthetic pathway involves the conversion of 2-aminophenol to 2-(bromomethyl)benzoxazole 1, followed by its transformation into the azide derivative 2. Subsequent reaction with functionalized arylalkynes 5a-d under Sharpless’s reaction conditions yields the desired compounds 6a-d. These benzoxazoles were then evaluated as G-Quadruplex DNA (G4) ligands by UV spectroscopy studies using a telomeric sequence (Tel22) as G4 model. We studied how the absorbance at λmax varies over time for the 6a-d/Tel22 mixtures at different molar ratios. Moreover we carried out melting experiments in order to point out any possible stabilization effects arising by ligand interaction. Our findings indicate that Tel22 is slighlty but significantly stabilized by compound 6b at a 1:1 ratio. Furthermore for 6b, these results align well with in silico predictions suggesting that the ligand acts as groove binder interacting with six guanosine residues of the telomeric model.

Effect of different substituent on the ESIPT process and fluorescence features of 2-(2-hydroxyphenyl)benzoxazole derivatives: A DFT/TD-DFT study

In this contribution, four derivatives of 5′-(para-R-Phenylene) vinyl-2-(2′-hydroxyphenyl) benzoxazole (PVHBO) were ingeniously designed by introducing two electron-withdrawing substituents and two electron-donating substituents, aiming to investigate the influence of different substituents on the photophysical properties of PVHBO and the excited state intramolecular proton transfer (ESIPT) process via the density functional theory (DFT) and time-dependent DFT (TD-DFT) methods. By utilizing the geometric parameters and the simulated infrared (IR) spectra, we compared the intramolecular hydrogen bonds (IHBs) strengths in the S0 and S1 states of the molecules. Via conducting the hole-electron analysis, the reduction in fluorescence intensity for the enol and keto forms of PVHBO, PVHBO-MeO, and PVHBO-NH2 were also well explicated. Besides, the potential energy curves (PECs) and corresponding transition state (TS) structures for both S0 and S1 states were also constructed to accurately obtain energy barriers of forward and reversed proton transfer processes. The calculated absorption and fluorescence spectra also show that PVHBO-NH2 has the largest Stokes shifts of 158 nm and 219 nm in both the enol and keto states, with a significant increase in fluorescence intensity observed upon the induction of electron-withdrawing groups. Through this work, it can provide the theoretical basis for the design of novel luminescent materials.

Synthesis and characterization of new purple and green heterocyclic dyes for dye-sensitized solar cells

Due to the growing demand for energy from industrial activities, solar energy has gained increasing attention globally. In recent years, heterocyclic dyes have gained attention due to their potential use as organic photosensitizers in dye-sensitized solar cells (DSSCs). To develop new and effective synthetic dyes for DSSCs, a study was conducted to create new purple dyes 8-(4-chlorophenyl)-5-(hydroxyimino)-3H-imidazo[4′,5′:3,4]benzo[1,2-c]isoxazol-4(5H)-ylidene)-2-arylacetonitriles. These dyes were synthesized by reacting nitro derivatives of imidazo benzoxazole with arylacetonitriles in an alkaline media. Additionally, new fluorescent heterocyclic systems 3-(4-chlorophenyl)-6H-imidazo[4,5-a]isoxazolo[4,3-c]acridine-7-carbonitriles were obtained by heterocyclization of the purple dyes with SOCl2. The highest yield achieved in the synthesis of the title dyes is 74 %. The structures of the new purple and green heterocyclic dyes were confirmed through elemental analysis and spectroscopic data. The photophysical properties of the dyes were investigated using a UV–visible spectrophotometer and a fluorophotometer. The electrochemical characteristics of the purple dyes and fluorescent heterocyclic systems were also studied using cyclic voltammetry. The geometries of the dyes, as well as their highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energy levels, were determined through theoretical calculations using density functional theory (DFT). Furthermore, the photovoltaic performance parameters of the new dyes were examined by analyzing their incident photon-to-current efficiency (IPCE) spectra and current-voltage (I-V) curves. The experimental results showed that the purple dyes exhibited remarkable photovoltaic performances, up to 6.55 %.

Ruthenium(II) Polypyridyl Complexes with Benzoxazole Derivatives and Non-Innocent Ligands as Effective Antioxidants in Human Neuroblasts.

Ruthenium(II) polypyridyl complexes continue to raise increasing interest for the encouraging results in several biomedical areas. Considering their vast chemical-physical repertoire, in particular the possibility to switch from the sensitization of reactive oxygen species (ROS) to ROS-scavenging abilities by tuning the nature of their ligands, it is therefore surprising that their potential as antioxidants has not been largely investigated so far. Herein, we explored the antioxidant behaviour of the novel ruthenium compound [Ru(dbpy)(2,3-DAN)Cl]PF6 (Ru1), featuring a benzoxazole derivative (dpby=2,6-bis(4-methyl-2-benzoxazolyl)pyridine) and the non-innocent 2,3-diamminonaftalene (2,3-DAN) ligand, along with the reference tpy-containing analogue [Ru(tpy)(2,3-DAN)Cl]PF6 (Ru2) (tpy=2,2':6',2''-terpyridine). Following the synthesis and the electrochemical characterization, chemical antioxidant assays highlighted the beneficial role of dpby for the ROS-scavenging properties of Ru1. These data have been corroborated by the highest protective effect of Ru1 against the oxidative stress induced in SH-SY5Y human neuroblastoma, which exerts pro-survival and anti-inflammatory actions. The results herein reported highlight the potential of Ru1 as pharmacological tool in neurodegenerative diseases and specially prove that the antioxidant properties of such compounds are likely the result of a non-trivial synergetic action involving the bioactive ligands in their chemical architectures.

Photophysics of Benzoxazole and Dicyano Functionalised Diketopyrrolopyrrole Derivatives: Insights into Ultrafast Processes and the Triplet State.

Diketopyrrolopyrrole (DPP) functionalised with an electron donating unit acts as a donor-acceptor molecules that have shown potential for application in dyes and photovoltaics. These molecules offer broad absorption/emission properties and structure-dependent dynamics. In this study, we used femtosecond pump-probe spectroscopy to investigate the photo-initiated dynamics of thiophene linked DPP derivatives. The thio-DPPs are further functionalised by different electrons withdrawing terminal groups, namely benzoxazole and thiophene dicyanide. The benzoxazole derivative is strongly emissive and directly relaxes directly to the ground state chloroform solution. Thiophene dicyanide derivative exhibits distinct spectral evolution in the first 10 ps, associated with structural and vibronic process. Later, it crosses over to the triplet state with a yield of 20 %. In the solid-state (thin film), we observed a signal that resembles singlet fission. However, upon careful analysis of temperature-dependent steady state absorbance spectra, we conclude that these features are due to laser-induced thermal artifacts. We describe a simplified excited state evolution in the thin film that does not include any additional excited states. These findings have significant implications for the analysis of triplet formation, which plays a major role in the photophysics of many organic materials.

DFT Calculations, Molecular Docking, and Pharmacological Properties Investigation for 5-Benzoxazolecarboxylic Acid as a Target Anti-Cancer Agent

In this study, the electronic properties of the 5-Benzoxazolecarboxylic acid molecule, a benzoxazole derivative, were calculated at the DFT/B3LYP/6-311++G(d,p) level of theory. Electronic properties and chemical reactivity of the optimized structure, such as Frontier molecular orbital (FMO), global and chemical reactivity descriptors, molecular electrostatic potential (MEP), and charge analyses (APT, Hirshfeld, and NBO), were investigated. Also, electronic properties are supported by electron localization function (ELF) and localized orbital locator (LOL) analyses. Toxicity effects such as mutagenic, tumorigenic, irritant, reproductive effect, and physicochemical properties such as druglikeness and drugscore were investigated. Molecular docking studies were conducted with the vascular endothelial growth factor receptor VEGFR-2 and the PARP-2 inhibitor, which is involved in many critical cellular processes, including DNA single-stranded fracture repair and cell death control, and its effectiveness in cancer treatment was investigated.

Synthesis, structure and mesogenic properties of benzoxazole derivatives

ABSTRACT Two new homologous series of mesogenic compounds, alkanoic acid 4-{[4-(6-chloro-benzooxazol-2-yl)-phenylimino]-methyl}-3-hydroxy-phenyl ester (3a-c) and alkcanoic acid 4-(6-chloro-benzooxazol-2-yl)-3-hydroxy-phenyl ester (5a-b) incorporating benzoxazole heterocyclic have been prepared and FT-IR, NMR, and MS spectrometry have been used to study the molecular structures. The mesogenic behaviour was examined using POM, DSC, and PXRD (variable temperature) techniques. To evaluate its impact on thermal behaviour and mesomorphic properties, the imine linking group of derivatives was modified and investigated. Enantiotropic SmA is observed by the members of Series-I, while those of series-II show monotropic SmA mesomorphism. These compounds were also examined for their absorption and fluorescent properties. The absorption and photoluminescence spectra of compounds 3a-c occurred at 345 nm and 410 nm, whereas in the case of 5a-b occurred at 325 nm and 370 nm respectively. The GAUSSIAN-09 programme has been utilised to perform DFT calculations at B3LYP level for the purpose of obtaining the stable electronic structures of 3a and 5a.

Benzimidazole and Benzoxazole Derivatives Against Alzheimer's Disease.

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.

Design, Synthesis, and Biological Evaluation of 2-Phenoxyalkylhydrazide Benzoxazole Derivatives as Quorum Sensing Inhibitors with Strong Antibiofilm Effect.

With the increasing problem of bacterial resistance to traditional antibiotics, there is an urgent need for new antibacterial agents with novel mechanisms to treat infections caused by drug-resistant bacteria. In this paper, we designed and synthesized 2-phenoxyalkylhydrazide benzoxazole derivatives and evaluated their quorum sensing inhibition activity. Among them, 26c at a concentration of 102.4 μg/mL not only inhibited the production of pyocyanin and rhamnolipid by 45.6% and 38.3%, respectively, but also suppressed 76.6% of biofilm production at 32 μg/mL. In addition, 26c did not affect bacterial growth, but in a mouse model infected with P. aeruginosa PAO1, it could help ciprofloxacin effectively eliminate the living bacteria. In the targeting experiment, 26c could inhibit the fluorescence intensity of PAO1-lasB-gfp and PAO1-pqsA-gfp in a concentration-dependent manner, indicating that the compound acts on the quorum sensing system. Overall, 26c is worthy of further investigation as a quorum sensing inhibitor with strong antibiofilm effect.

Structure-based inhibition of acetylcholinesterase and butyrylcholinesterase with 2-Aryl-6-carboxamide benzoxazole derivatives: synthesis, enzymatic assay, and in silico studies.

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 IC50 12.62 nM for AChE and IC50 25.45 nM for BChE (whereas donepezil was 69.3 nM and 63.0 nM, respectively). Additionally, compound 36 had docking values ​​of - 7.29kcal/mol for AChE and - 6.71kcal/mol for BChE (whereas donepezil was - 6.49kcal/mol and - 5.057kcal/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.

Synthesis and biological evaluation of radioiodinated benzoxazole and benzothiazole derivatives for imaging myelin in multiple sclerosis

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that results from destruction of the myelin sheath. Due to heterogeneity of the symptoms and course of MS, periodic monitoring of disease activity is important for diagnosis and treatment. In the present study, we synthesized four radioiodinated benzoxazole (BO) and benzothiazole (BT) derivatives, and evaluated their utility as novel myelin imaging probes for single photon emission computed tomography (SPECT). In a biodistribution study using normal mice, three compounds ([125I]BO-1, [125I]BO-2, and [125I]BT-2) displayed moderate brain uptake (2.7, 2.9, and 2.8% ID/g, respectively) at 2 min postinjection. On ex vivo autoradiography using normal mice, [125I]BO-2 showed the most preferable ratio of radioactivity accumulation in white matter (myelin-rich region) versus gray matter (myelin-deficient region). In addition, the radioactivity of [125I]BO-2 was reduced in the lysophosphatidylcholine-induced demyelination region. In conclusion, [123I]BO-2 demonstrated the fundamental characteristics of a myelin imaging probe for SPECT.

Synthesis and antibacterial activities of novel hybrid molecules based on benzothiazole, benzimidazole, benzoxazole, and pyrimidine derivatives, each connected to N-arylacetamide and benzoate groups

Novel benzimidazoles, benzothiazoles, and benzoxazoles linked to N-arylacetamide were synthesized in good yields by reacting a series of 2-oxo-2-(arylamino)ethyl 4-formylbenzoates with o-phenylenediamine, 2-aminothiophenol, or 2-aminophenol in ethanol at reflux in the presence of NaHSO3. Attempts to use the new aldehydes as adaptable precursors for the synthesis of fused dihydropyran or fused dihydropyridine via Michael or Hantzsch's reactions were unsuccessful; instead, the processes produced the corresponding arylidene derivatives. The structures of the novel compounds were verified with a variety of spectra. All synthesized compounds were evaluated for antibacterial activity against four different bacterial strains. Compound 6a had good activity against Escherichia coli in an agar diffusion assay, with an inhibitory zone width of 30 mm compared to ofloxacin (20 mm). Compounds 18a and 18b were most effective against Bacillus subtilis, with MICs of 156.3 and 312.5 µg/mL, respectively. Molecular docking investigations demonstrated that compounds 6a, 18a, and 18b had high binding affinities for bacterial tyrosyl-tRNA synthetase and DNA gyrase.