Oxazole Moiety Research Articles

Membrane-Targeting Amphiphilic Honokiol Derivatives Containing an Oxazole Moiety as Potential Antibacterials against Methicillin-Resistant Staphylococcus aureus.

Infections with methicillin-resistant Staphylococcus aureus (MRSA) are becoming increasingly serious, making the development of novel antimicrobials urgent. Here, we synthesized some amphiphilic honokiol derivatives bearing an oxazole moiety and investigated their antibacterial and hemolytic activities. Bioactivity evaluation showed that E17 possessed significant in vitro antibacterial activity against S. aureus and MRSA, along with low hemolytic activity. Moreover, E17 exhibited rapid bactericidal properties and was not susceptible to resistance. Mechanistic studies indicated that E17 interacts with phosphatidylglycerol and cardiolipin of bacterial cell membranes, leading to changes in cell membrane permeability and polarization, increased intracellular ROS, and leakage of DNA and proteins, thus accelerating bacterial death. Transcriptome analysis further demonstrated that E17 has membrane-targeting effects, affecting the expression of genes related to cell membranes and ABC transporter proteins. Notably, in vivo activity showed that E17 has prominent anti-MRSA efficacy, comparable to vancomycin, and is expected to be a new anti-MRSA drug candidate.

Unidirectional photoisomerisation in a dual channel proton transfer molecule rhodamine B based Schiff Base: A ratiometric pH sensor

In this article we have presented the synthesis, characterisation and spectral study of a newly designed fluorophore, (E)-2-((3-(benzo[d]oxazol-2-yl)-5-bromo-2-hydroxybenzylidene)amino)-3′,6′-bis(diethylamino)spiro [isoindoline-1,9′-xanthen]-3-one (RHHBO) which has two possible six member intramolecular hydrogen bonded networks capable for dual channels proton transfer reaction − one towards the N atom of oxazole moiety and the other towards the N atom of rhodamine moity. Details steady state and time resolved spectral analysis of RHHBO and a comparison of spectral features of control compounds 2-(2-hydroxyphenyl)benzoxazole (HBO), (E)-4-bromo-2-(hydrazonomethyl)phenol (HBN) and (E)-2-((5-bromo-2-hydroxybenzylidene)amino)-3′,6′-bis(diethylamino)spiro[isoindoline-1,9′-xanthen]-3-one (RH) having only single proton transfer site reveal that excited state intramolecular proton transfer (ESIPT) in RHHBO occurs towards the rhodamine side but not towards the oxazole side. Interestingly, RHHBO shows different fluorescence colour in acidic and basic medium and hence can be used ratiometric emission based pH sensor.

Natural and synthetic 5-(3'-indolyl)oxazoles: Biological activity, chemical synthesis and advanced molecules.

5-(3'-Indolyl)oxazole moiety is a privileged heterocyclic scaffold, embedded in many biologically interesting natural products and potential therapeutic agents. Compounds containing this scaffold, whether from natural sources or synthesized, have demonstrated a wide array of biological activities. This has piqued the interest of synthetic chemists, leading to a large number of reported synthetic approaches to 5-(3'-indolyl)oxazole scaffold in recent years. In this review, we comprehensively overviewed the different biological activities and chemical synthetic methods for the 5-(3'-indolyl)oxazole scaffold reported in the literatures from 1963 to 2024. The focus of this study is to highlight the significance of 5-(3'-indolyl)oxazole derivatives as the lead compounds for the lead discovery of anticancer, pesticidal, antimicrobial, antiviral, antioxidant and anti-inflammatory agents, to summarize the synthetic methods for the 5-(3'-indolyl)oxazole scaffold. In addition, the reported mechanism of action of 5-(3'-indolyl)oxazoles and advanced molecules studied in animal models are also reviewed. Furthermore, this review offers perspectives on how 5-(3'-indolyl)oxazole scaffold as a privileged structure might be exploited in the future.

Lewis Acid-Driven Multicomponent Reactions Enable 2-Alkyl Chromanones with Anticancer Activities.

2-Alkyl chromanone scaffold has become prominent in pharmaceuticals and natural compounds. Consequently, devising robust strategies for synthesizing 2-alkyl chromanones remains crucial. Here, multicomponent reactions were employed to synthesize 2-alkyl chromanones containing an oxazole moiety using 3-formylchromones, amines, and N-propargylamides as reactants. This method utilizes readily available feedstocks with a catalytic amount of Zn(OTf)2 and exhibits an impressive substrate scope compared to existing methods. Importantly, the synthesized compounds demonstrated highly selective anticancer activity against the DU145 cell line.

Total Synthesis of Icumazole A Using a Modified Cadiot-Chodkiewicz Coupling.

The first total synthesis of myxobacteria metabolite icumazole A (1) is reported. Key steps in the route include an organocatalyzed asymmetric self-aldol reaction followed by an acetate aldol reaction to form the stereotriad present in the oxazole moiety, an intramolecular Diels-Alder reaction to form the isochromanone, and an acetylide addition and selective methylation. The final steps involved a high-yielding modified Cadiot-Chodkiewicz coupling and stereoselective reduction to secure the Z,Z-diene and afford 1.

New quinazolin-2,4-dione derivatives incorporating acylthiourea, pyrazole and/or oxazole moieties as antibacterial agents via DNA gyrase inhibition.

This article contributes to the search for new therapeutic agents for treatment of diseases caused by bacterial pathogens. In this study, a new series of compounds incorporating numerous bioactive moieties such as quinazolin-2,4-dione, acylthiourea linkage, and/or five membered nitrogen heterocycles (pyrazole and oxazole) 2-5a-c was described to identify new antibacterial drug candidates via inhibition of DNA gyrase enzyme. The precursor N-[N'-(2-cyano-acetyl)-hydrazinocarbothioyl]-4-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-benzamide 2 was prepared by treatment of compound 1 with ammonium thiocyanate and cyanoacetic acid hydrazide through multicomponent reaction (MCR). In addition, compounds 3a-d and 4a-b were synthesized by treatment of 2 with aromatic aldehydes and/or ketones through Knoevenagel reaction, affording high purity products in satisfactory yields. Moreover, new heterocyclic moieties such as pyrazole and/or oxazole attached to quinazolin-2,4-dione core 5a-c were synthesized by treatment of 3c with different nucleophilic reagents like hydrazine, phenyl hydrazine and hydroxyl amine, respectively. Subsequently, the obtained products were structurally characterized by IR, 1H-, 13C-NMR, and MS analyses. The minimum inhibitory concentration (MIC) and antibacterial potency of all compounds were estimated against two G-ve (E. coli and P. aeruginosa), and two G+ve bacteria (B. subtilis and S. aureus). Encouragingly, compound 3c demonstrated the best antibacterial activity against all the strains of the tested pathogenic bacteria at low concentrations compared with the standard drug, Ciprofloxacin. Electron withdrawing groups such as -NO2 and -Cl enhance the antibacterial activity. Next, a molecular docking study between the synthesized derivatives and the target enzyme, DNA gyrase enzyme (PDB: 2xct) was undertaken to investigate intermolecular interactions between the compounds and target enzyme.

Rosellosides A and B, two phenyloxazole glycosides from Glycyrrhiza inflata-derived fungus Rosellinia sp. Glinf021

Two new chlorinated phenyloxazole glycosides, named rosellosides A (1) and B (2), were isolated from the endophytic fungus Rosellinia sp. Glinf021, which was derived from the medicinal plant Glycyrrhiza inflata (Leguminosae). Both compounds were rare chlorinated polyketide glycosides bearing an oxazole moiety. Their structures were elucidated by analysis of the NMR and HRESIMS data, and their absolute configurations were determined by quantum chemical ECD calculations and X-ray crystallography.

Utilization of Co2+ doped Eu2O3 nanostructures and their effect on the dielectric and photoisomerization of liquid crystals

In this study, the effect of Co2+x:Eu2O3 (x = 5, 10 wt. %) bimetallic oxide nanostructures (NS) on dielectric and cis-trans photoisomerization of liquid crystals (LC) has been studied. First, the Co2+:Eu2O3 NS were synthesized by facile coprecipitation method, and then the as-synthesized NS were characterized by x-ray diffraction, scanning electron microscopy, x-ray photoelectron spectroscopy, Brunauer Emmett Teller, and UV-visible analytical techniques. New composite structures were prepared by doping Co2+:Eu2O3 (5, 10 wt. %) over liquid crystal (LC) molecules (compounds 4 and 5) containing oxazole moiety. Optical absorption spectra of liquid crystalline NS (LCNS) showed a maximum absorption peak (λmax) between 350 and 450 nm. A significant improvement in the dielectric constants (ɛ′ and ɛ″) was noticed for LC-4 (compound 4)/LC-5 (compound 5) doped with Co2+ (10 wt. %):Eu2O3 NS. The photoisomerization studies of the Co2+ (10 wt. %):Eu2O3 doped to LC-5 (LCNS-2) containing oxazole moiety showed enhanced properties in solution and exhibited photoisomerization in 40 s whereas reverse process (thermal back relaxation) takes 358 s. Furthermore, it was observed that semiconductor NS especially Co2+ (10 wt. %):Eu2O3 NS doped LC-compounds showed enhanced dielectric and photoisomerization properties and can be a potential candidate for optoelectronics and photonic applications.

Enigmazole Phosphomacrolides from the Marine Sponge Cinachyrella enigmatica.

Enigmazole B (1) and four new analogues, cis-enigmazole B (2), dehydroenigmazole B (3), enigmimide B (4), and enigmimide A (5), were isolated from the marine sponge Cinachyrella enigmatica. Their planar structures were elucidated by detailed NMR and MS data analyses, which established 1-3 to be oxazole-substituted 18-membered phosphomacrolides, while 4 and 5 were oxazole ring-opened congeners. The relative and absolute configurations in 1 were determined by a combination of chemical transformations and spectroscopic analyses. Photooxidation of the oxazole moiety in 1 gave enigmimide B (4), thus establishing that 4 has the same absolute configuration of 1. Enigmazole B (1) along with analogues 2 and 3 showed cytotoxicity against murine IC-2 mast cells with IC50 values of 3.6-7.0 μM. The enigmimides (4 and 5) and dephosphoenigmazoles did not show cytotoxicity (IC50 > 10 μM), implying that both the oxazole moiety and the phosphate group are necessary for the cytotoxicity of the enigmazole class macrolides.

Highly Regioselective Synthesis of 3,6‐Diaryl‐2‐(het)arylpyridines by aza‐Diels‐Alder Reactions between 6‐H‐1,2,4‐Triazine Dienes and 2‐Amino‐4‐aryloxazole‐Based Dienophiles

AbstractA solvent‐free reaction between C6‐unsubstituted 5‐aryl‐1,2,4‐triazines and 2‐amino‐4‐aryloxazoles at high temperature was studied. The reaction proceeds via inverse electron demand aza‐Diels‐Alder reaction between the oxazole moiety as dienophile and the 1,2,4‐triazine moiety as diene with the highly regioselective formation of 3,6‐diarylpyridines in up to 60 % isolated yield. The structure of one of the key‐products was proven by the X‐ray diffraction analysis, and the mechanism of the transformation was proposed. The reaction proceeds well for both 6‐aryl and 6‐hetaryl‐1,2,4‐triazines in the presence of the electron acceptor substituent at the position 3. In the case of the donor substituent in position 3, the pyridine yields are significantly reduced. In the case of 5,6‐nonsubstituted 1,2,4‐triazines, the triazine cycle is degraded without product formation. The high regioselectivity of the reaction as well as solvent‐free conditions are valuable advantages of the present synthetic approach.

Recent Developments in Oxazole Derivatives as Anticancer Agents: Review on Synthetic Strategies, Mechanism of Action and SAR Studies.

Cancer is the world's third deadliest disease. Despite the availability of numerous treatments, researchers are focusing on the development of new drugs with no resistance and toxicity issues. Many newly synthesized drugs fail to reach clinical trials due to poor pharmacokinetic properties. Therefore, there is an imperative requisite to expand novel anticancer agents with in vivo efficacy. This review emphasizes synthetic methods, contemporary strategies used for the inclusion of oxazole moiety, mechanistic targets, along with comprehensive structure-activity relationship studies to provide perspective into the rational design of highly efficient oxazole-based anticancer drugs. Literature related to oxazole derivatives engaged in cancer research is reviewed. This article gives a detailed account of synthetic strategies, targets of oxazole in cancer, including STAT3, Microtubules, G-quadruplex, DNA topoisomerases, DNA damage, protein kinases, miscellaneous targets, in vitro studies, and some SAR studies. Oxazole derivatives possess potent anticancer activity by inhibiting novel targets such as STAT3 and Gquadruplex. Oxazoles also inhibit tubulin protein to induce apoptosis in cancer cells. Some other targets such as DNA topoisomerase enzyme, protein kinases, and miscellaneous targets including Cdc25, mitochondrial enzymes, HDAC, LSD1, HPV E2 TAD, NQO1, Aromatase, BCl-6, Estrogen receptor, GRP-78, and Keap-Nrf2 pathway are inhibited by oxazole derivatives. Many derivatives showed excellent potencies on various cancer cell lines with IC50 values in nanomolar concentrations. Oxazole is a five-membered heterocycle, with oxygen and nitrogen at 1 and 3 positions, respectively. It is often combined with other pharmacophores in the expansion of novel anticancer drugs. In summary, oxazole is a promising entity to develop new anticancer drugs.

Stimuli‐Responsive Polycycles Based on Hetero‐Buckybowl Trithiasumanene

Main observation and conclusionStimuli‐responsive molecules are highly desirable in different scenario such as smart materials, bio‐imaging, and environment monitoring. Herein, a series of hetero polycycles which show optical response toward chemical stimuli are synthesized from trithiasumanene (TTS). The TTS is transformed into ortho‐quinone form, which then undergoes three‐component Debus‐Radziszewski reaction with aldehydes and ammonia to give oxazole‐fused TTS (2—6). The thiophene rings on 3—5 are selectively oxidized to thiophene‐S,S‐dioxides, affording 3‐3O2—5‐3O2. It is found that the electronic structures of these compounds are governed by the substituents on oxazole moiety and oxidation state of thiophene ring. Moreover, these hetero polycycles exhibit optical response toward different chemical stimuli. Particularly, compounds 6 and 3‐3O2 can serve as fluorescence detectors for harmful chemicals sulfide ions (S2–/HS–) and aniline, respectively. This work indicates that TTS is a promising precursor for the creation of responsive materials.

Discovery of novel trimethoxyphenylbenzo[d]oxazoles as dual tubulin/PDE4 inhibitors capable of inducing apoptosis at G2/M phase arrest in glioma and lung cancer cells.

To discover PDE4/tubulin dual inhibitors with novel skeleton structures, 7-trimethoxyphenylbenzo[d]oxazoles 4a-u and 4-trimethoxyphenylbenzo[d]oxazoles 5a-h were designed and synthesized by migrating the trimethoxyphenyl group of TH03 to the benzo[d]oxazole moiety. Among these compounds, approximately half of them displayed good antiproliferative activities against glioma (U251) and lung cancer (A549 and H460) cell lines. The structure-activity relationships of trimethoxyphenylbenzo[d]oxazoles led to the identification of 4r bearing indol-5-yl side-chain as a novel dual PDE4/tubulin inhibitor, which exhibited satisfactory antiproliferative activities against glioma (IC50=300±50nM) and lung cancer (average IC50=39.5nM) cells. Further investigations revealed that 4r induced apoptosis at G2/M phase arrest and disrupted the microtubule network. The preliminary mechanism of action showed that 4r down-regulated the expression of cyclin B1 and its upstream regulator gene cdc25C in A549.

2-Aminooxazoles as novel dienophiles in the inverse demand Diels–Alder reaction with 1,2,4-triazines

High temperature coupling of 6-aryl-5-cyano-3-(pyridin-2-yl)-1,2,4-triazines with 2-amino-4-aryloxazoles proceeds as the inverse demand Diels–Alder reaction between the oxazole moiety as dienophile and the 1,2,4-triazine moiety as diene to construct new 4,5-diaryl-6-cyano-3-hydroxypyridin-2-yl fragment. A reaction mechanism is proposed, and the structure of the key-product is proved by the X-ray diffraction analysis.

Synthesis, Characterization and Anti-Inflammatory Study of New Heterocyclic Coumarin Derivatives

The inflammation is one of the most central processes in animal cells defense versus certain injuries orinfections of microbes. The most essential metabolic precursor for many inflammatory pathways is PGH2(prostaglandin), which catalytic synthesis from the AA (arachidonic acid) by COX enzymes. COX can bedivided in to three isomer COX-1 has important role in many physiological function like hemostasis, plateletaggregation, and protection of gastric mucosa, COX-2 when stimulate cause formation of PGE2 excessively,with other prostaglandin then decrease the pain threshold and nerve ending sensitization, which inducepain, increase permeability of vascular and then enhance the inflammatory associated diseases pathway, andCOX-3 has special characteristic, its higher sensitivity to acetaminophen and present in brain. The NSAIDsare therapeutic agents used for the treatment of inflammation, pain, and fever, they work by decreasing theproduction of prostaglandins due to inhibiting the function of the cyclooxygenase (COX) enzyme, we havetwo types nonselective and selective COX-2 inhibitors. In order to design new agents with no or low sideeffect, the COX-2 selectivity should be increased, this achieved by design molecule structurally similar toapproved selective COX-2 inhibitors. The synthetic compound in this study contain three pharmacophores,a nucleus of coumarin and substituted oxazole moiety, separated by a hydrazonoethyl spacer, which havestructural similarity properties to selective COX-2 inhibitors.

Relationships of the Enantioselective Retention of Chiral Oxazolopyrroloquinolones on a Stationary Phase with Grafted Antibiotic Ristocetin A

A study is performed of mechanisms of the retention and separation of enantiomers of a series of chiral oxazolopyrroloquinolones on a stationary phase with grafted macrocyclic antibiotic ristocetin A under the conditions of high-performance liquid chromatography using water–acetonitrile mobile phases. It is found that the dependence of the retention factor on the concentration of CH3CN in the mobile phase has a U-shape. An explanation of this phenomenon is given. The thermodynamics of the oxazolopyrroloquinolone adsorption in different parts of this dependence is studied. It is assumed that the adsorption complex forms through inclusion of the oxazole moiety of the adsorbate molecule in the chiral cavity of the grafted selector. The effect the nature of the substituent on the chiral carbon atom in oxazolopyrroloquinolones on enantioseparation is discussed.

Synthesis and antiseizure effectevaluation of nonimidazole histamine H3 receptor antagonists containing the oxazole moiety.

The use of histamine H3 receptor (H3 R) antagonists is becoming a promising therapeutic approach for epilepsy. In this paper, a series of novel nonimidazole H3 R antagonists was synthesized and screened as antiepileptic drugs. All of these prepared antagonists displayed micromolar or submicromolar H3 R antagonistic activities in the cAMP response element luciferase screening assay. Compounds 5a (IC50 = 0.11 μM), 5b (IC50 = 0.56 μM), and 5f (IC50 = 0.78 μM) displayed the most potent H3 R antagonistic activities, with considerable potency when compared with pitolisant (IC50 = 0.51 μM). In the maximal electroshock (MES)-induced seizure model, compounds 5c, 5e, and 5g showed obvious protection for the electrostimulated mice, and the protection of 5g against the MES-induced seizures was fully abrogated when mice were cotreated with R-(α)-methyl-histamine, a central nervous system-penetrant H3 R agonist, suggesting that the potential therapeutic effect of 5g was observed to work through H3 R. These results indicate that the attempt to find a new antiepileptic drug among H3 R antagonists is practicable, but it is necessary to consider the log P of the molecules to ensure penetration of the blood-brain barrier.

4-Methylumbelliferone fused oxazole thioether derivatives: synthesis, characterization and antifungal activities

Series of thioether derivatives containing 4-methylumbelliferone fused oxazole moiety were designed and synthesised, their structures were fully characterized by 1H NMR, 13C NMR and HR-ESI-MS as well. Moreover, the in vitro antifungal potency of the title compounds were preliminarily evaluated for their possible use as a fungicide. Meanwhile, ethyl thioethers 3aa and 3ba displayed remarkable inhibitory effect against the mycelium growth of Valsa mali and Botrytis cinerea with EC50 of 12–16 μg/mL. Furthermore, compounds 3aa and 3ba also exhibited > 88% protective and curative effect against B. cinerea on tomato fruits at 90 μg/mL. Additionally, the environmental toxicity of the title compounds against the brine shrimp Artemia salina were evaluated as well. The results indicated that most of the title compounds exhibited weak toxic to aquatic organism A. salina.

Synthesis, characterization of new nicotinamide-oxazole analogs, and their antimicrobial activity

Identification of a novel antimicrobial molecule is vital to research due to contaminated agro related products and injurious pathogens. Especially candida albicans is most common infective fungi in the present world, that cause hospital-acquired infections. There is a medical and biological need for the discovery of novel antimicrobial drugs with high potent in nature. This effort involved the synthesis of scaffold molecule, in which Vitamin B3 and oxazole plays vital role as pharmacophore moiety, where 2-(Nicotinamido) oxazole-4-Carboxylic acid coupled from pyridine–3-carboxylic acid (Nicotinic acid) and 2-aminooxazole derivative. Then it is characterized by mass spectra, 1H NMR spectroscopy and carried for the growth control ability study against microbial targets such as fungal, and bacterial targets. The Zone of inhibition measured in millimeter for the serially diluted solution of the compound. From the outcomes, the compound (5i) displayed 35mm of inhibition zone area but standard fluconazole showed 29mm for 250 ppm solution. The outcome revealed that the amide bond and oxazole moiety turns as imperative pharmacophore besides showing decent inhibition activities.

Design and Synthesis of Pentacycloundecane Cage Compound Containing Oxazole Moiety

Design and Synthesis of Pentacycloundecane Cage Compound Containing Oxazole Moiety