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A versatile method has been developed for the synthesis of morpholine‐dihydropyrimidine hybrids, 3‐benzyl‐6‐methyl‐5‐(morpholine‐4‐carbonyl)‐4‐phenyl‐3,4‐dihydropyrimidin‐2(1H)‐one, through the construction of dihydropyrimidine (DHPM) via the guanidine‐based Biginelli reaction followed by sodium tertiary butoxide mediated substitution of the benzyl group at the 3rd position of DHPM ring. This substitution approach represents a novel method for obtaining N‐substituted Biginelli products in good yields (72%–84%). Further, the ester group was subjected to intergroup conversion by morpholine using in situ generated diisobutyl(morpholino)aluminum. Notably, this reaction exhibited tolerance to various functional groups, resulting in the corresponding derivatives of dihydropyrimidine–morpholine hybrids in excellent yield (62%–82%). [ABSTRACT FROM AUTHOR]

The new type of the four‐component tandem Knoevenagel–Michael reaction was discovered: the transformation of arylaldehydes, N,N′‐dimethylbarbituric acid, malononitrile, and morpholine in alcohols and other organic solvents without any other additives at ambient temperature resulted in the selective formation of a new substituted unsymmetrical ionic scaffold with two pharmacology‐active heterocyclic rings. This new four‐component reaction is a simple and efficient route to a previously unknown substituted ionic unsymmetrical scaffold containing N,N′‐dimethylbarbituric acid and morpholine. These ionic scaffolds are promising for various biomedical applications, for example, as anticonvulsants and anti‐inflammatory drugs, as well as anti‐AIDS agents. In this research, we also accomplished the efficient cyclization of morpholin‐4‐ium 5‐(2,2‐dicya‐no‐1‐arylethyl)‐1,3‐dimethyl‐2,6‐di‐oxo‐1,2,3,6‐tetrahydro‐pyrimidin‐4‐olates by the action of NBS–NaOAc system, with the formation of 5,7‐dimethyl‐4,6,8‐trioxo‐2‐aryl‐5,7‐diazaspiro[2.5]octane‐1,1‐dicarbonitriles in 83%–98% yields. In the final stage of our research, direct one‐pot multicomponent transformation of benzaldehydes, N,N′‐dimethylbarbituric acid, and malononitrile into spirobarbituric cyclopropanes was accomplished in 75%–97% yields. The spiro‐barbituric cyclopropanes are potentially active as remedies against various inflammatory, infectious, immunological, or malignant diseases. [ABSTRACT FROM AUTHOR]

Over the past few years, numerous bacterial strains have become resistant to selected drugs from various therapeutic groups. A potential tool in the fight against these strains is antimicrobial photodynamic therapy (APDT). APDT acts in a non-specific manner by generating reactive oxygen species and radicals, thereby inducing multidimensional intracellular effects. Importantly, the chance that bacteria will develop defense mechanisms against APDT is considered to be low. In our research, we performed the synthesis and physicochemical characterization of curcumin derivatives enriched with morpholine motifs. The obtained compounds were assessed regarding photostability, singlet oxygen generation, aggregation, and acute toxicity toward prokaryotic Aliivibrio fischeri cells in the Microtox® test. The impact of the compounds on the survival of eukaryotic cells in the MTT assay was also tested (WM266-4, WM115—melanoma, MRC-5—lung fibroblasts, and PHDF—primary human dermal fibroblasts). Initial studies determining the photocytotoxicity, and thus the potential APDT usability, were conducted with the following microbial strains: Candida albicans, Escherichia coli, Staphylococcus aureus, Streptococcus pneumoniae, and Pseudomonas aeruginosa. It was noted that the exposure of bacteria to LED light at 470 nm (fluence: 30 J/cm2) in the presence of quaternized curcumin derivatives at the conc. of 10 µM led to a reduction in Staphylococcus aureus survival of over 5.4 log. [ABSTRACT FROM AUTHOR]

In the presence of catalytic amounts of a secondary amine (e. g. morpholine), skipped diynones undergo hydration/cyclization in aqueous acetonitrile to form γ‐pyrones in moderate to excellent yields (30–92 %). The first step of the process involves a trans‐stereoselective conjugate‐addition of morpholine to the ynone to form an intermediate E‐enaminone. Gradually this intermediate reacts with H2O yielding an acetylenic β‐diketone via nucleophilic vinylic substitution. Under the basic reaction conditions, acetylenic β‐diketones cyclize to γ‐pyrones. Primary amines fail to promote efficiently the process, as the initially formed Z‐configurated enaminones are reluctant to react smoothly under standard reaction conditions. [ABSTRACT FROM AUTHOR]

The thermal regeneration of CO2 sorbent is the most energy-consuming step in the CO2-capturing process. Although the addition of an acid can induce CO2 release, it does not regenerate the sorbent because the acid forms a salt with the basic sorbent and diminishes its capability for capturing CO2. In this work, a novel approach based on thermally enhanced acidity was studied. This approach utilizes an additive that does not affect the sorbent at room temperature, but its acidity significantly increases at elevated temperatures, which assists the thermal release of CO2. M-cresol was added to an aqueous solution of morpholine. The CO2 capture and release of the mixture were compared to those of a control solution without m-cresol. The amounts of carbamate, bicarbonate, and unreacted morpholine were quantitatively determined using 1H NMR and weight analysis. The results showed that m-cresol did not affect the reactivity of morpholine in the formation of carbamate with CO2 at room temperature. At elevated temperatures, the acidity of m-cresol increased according to Van't Hoff's equation, which resulted in a significantly higher rate of CO2 release than that of the control. Given the low cost of m-cresol and its derivatives, this approach could lead to practical technology in the near future. [ABSTRACT FROM AUTHOR]

The current study evaluates the effect of morpholine on saliva-contaminated acrylic resin repaired with light-cured resin composites. Sixty rods of self-curing acrylic resin were fabricated and assigned into four groups of fifteen specimens and surface-treated with saliva, phosphoric acid (PH), morpholine (MR), liquid MMA monomer, and a universal adhesive agent (UA, Singlebond Universal) based on the following techniques: group 1, saliva; group 2, saliva + PH + MMA + UA; group 3, saliva + MMA + UA; and group 4, saliva + MR + MMA + UA. An Ultradent model was placed at the center of the specimen, and then the resin composite was pressed and light-cured for 20 s. A mechanical testing device was used to evaluate the samples' shear bond strength (SBS) scores. The debonded specimen areas were inspected under a stereomicroscope to identify their failure mechanisms. The data were assessed by employing the one-way ANOVA approach, and the significance level (p < 0.05) was established with Tukey's test. The greatest SBS scores for group 2 (30.46 ± 2.26 MPa) and group 4 (32.10 ± 2.72 MPa) did not differ statistically significantly from one another. The lowest SBS recorded for group 1 was 1.38 ± 0.87 MPa. All of the fractured samples in group 1 had an adhesive failure profile. Groups 2 and 4 had the greatest percentages of cohesive failures. This study concluded that applying phosphoric acid and morpholine to sandblasted self-curing acrylic resin contaminated with saliva before MMA and universal adhesive agents are applied is the most efficient protocol for stimulating SBS when it is repaired with light-cured resin composites. [ABSTRACT FROM AUTHOR]

New triazole-based tridentate ligands were synthesized, and their crystal structures determined. Through comparison with the crystal structures of the starting materials and related published ligands, dependencies of intermolecular interactions based on the substitution patterns of the triazole motif were identified. In addition to π-stacking interactions, hydrogen bonding, and C–H···π interactions emerged as key players in intermolecular interactions. The observed variations in these interactions will aid in the design of platinum(II) complexes with specific properties. [ABSTRACT FROM AUTHOR]

The ultrasonic induced oxidative addition reaction of C60 fullerene to tris(hydroxymethyl)-aminomethane in a toluene—DMF solvent mixture in the presence of LiOH and Pb(OAc)4 at room temperature in an aerobic environment gave 47% yield of the C60 fullerene monoadduct containing in its structure a morpholine fragment annulated to the [60]fullerene core. [ABSTRACT FROM AUTHOR]

4‐(trimethylsilyl)morpholine O(CH2CH2)2NSi(CH3)3 (TMSM) was investigated as a single‐source precursor for SiCNO films synthesis. Optical emission spectroscopy of plasma generated from TMSM/He, TMSM/H2, and TMSM/NH3 gas mixtures revealed the presence of N2, CH, H, CN, and CO species. The last two are suggested to be responsible for the lowering of carbon concentration in the films in comparison with the precursor. The refractive index ranged from 1.5 to 2.0, and bandgap varied from 2.0 to 4.6 eV, which pointed that some of the films can be used as antireflective coatings in silicon photovoltaic cell technologies and dielectric layers in electronic devices. [ABSTRACT FROM AUTHOR]

A novel Deep Eutectic Solvent (MTPPBr/HGA-DES) was prepared by a mixture of methyl triphenylphosphonium bromide (MTPPBr) and hypogallic acid (HGA: 2,3-dihydroxybenzoic acid). The eutectic point phase diagram showed that the one mole of MTPPBr to two moles of HGA is the best mole ratio for the synthesis of a novel DES. Then, MTPPBr/HGA-DES was characterized by the FT-IR, TGA/DTA, densitometer, eutectic points, and 1H NMR techniques, and used as a novel catalyst for the green synthesis of new pyrano[2,3-d]pyrimidines 2(a-j)via a one-pot four-component condensation reaction of 4-hydroxycoumarin, barbituric acid, morpholine and benzaldehydes at 80 °C in solvent-free conditions. [ABSTRACT FROM AUTHOR]

Chemoselective peptide ligation using ligation auxiliaries is a powerful methodology to extend the scope of native chemical ligation beyond ligation at Cys. Herein, we report the development of novel amino acids containing an N‐mercaptophenethyl (MPE)‐type auxiliary and protecting groups (i. e. tert‐butyloxycarbonyl (Boc), 1,3‐thiazolidine (Thz), and allyloxycarbonyl (Alloc)). These developed amino acids can be introduced into a peptide via 9‐fluorenylmethoxycarbonyl‐based solid‐phase peptide synthesis, enabling deprotection and native chemical ligation in one pot. The combination of Thz‐type and Alloc‐type acids enables sequential peptide ligation, which is applicable to the synthesis of peptides branched from a Lys side chain. We also found that the multiple N‐MPE groups are efficiently cleaved upon treatment with tris(2‐carboxyethyl)phosphine and morpholine in the presence of SnCl2. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a severe endocrine disease that affects more and more people every year. Modern medical chemistry sets itself the task of finding effective and safe drugs against diabetes. This review provides an overview of potential antidiabetic drugs based on three heterocyclic compounds, namely morpholine, piperazine, and piperidine. Studies have shown that compounds containing their moieties can be quite effective in vitro and in vivo for the treatment of diabetes and its consequences. [ABSTRACT FROM AUTHOR]

As a vital biological molecule, H2O2(Hydrogen Peroxide) is involved in different physiological and pathological processes. And in addition to this, H2O2 is suitable for medical wound disinfection, environmental disinfection and food disinfection. Accordingly, it is of high significance to conveniently and effectively detect H2O2 in the environment and organisms. This subject synthesised a fluorescent probe Pyrimidine-Se by using selenomorpholine and pyrimidine dye, which detect H2O2 in an aqueous environment. Pyrimidine-Se has a large Stokes shift (Δλ = 155 nm), which can specifically and quickly quantitatively detect H2O2. When the probe Pyrimidine-Se reacted with H2O2, the Se(II) in the selenomorpholine was oxidised to Se(IV), so the electron withdrawing ability of the electron withdrawing group of Pyrimidine-Se was improved, and the fluorescence intensity of the probe were enhanced. Interestingly, Se(IV) can be reduced by GSH (Glutathione) to Se(II) to quench the fluorescence, and this redox cycle can continue several times, which indicated that it can have a potential of real-time monitoring the redox state in vivo. The probe was also satisfactorily used to detect H2O2 in Argentina Bloodfin larvaes and abnormal H2O2 content in some organs was detected. [ABSTRACT FROM AUTHOR]

In this study, we synthesized 15 novel quinazoline‐morpholinobenzylideneamino hybrid compounds from methyl anthranilate and we assessed their cytotoxicity via in vitro assays against A549 and BEAS‐2B cell lines. Molecular docking studies were conducted to evaluate the protein‐ligand interactions and inhibition mechanisms on nine different molecular targets, while molecular dynamics (MD) simulations were carried out to assess the stability of the best docked ligand–protein complexes. Additionally, ADME prediction was carried out to determine physicochemical parameters and drug likeness. According to the cytotoxicity assays, compound 1 (IC50 = 2.83 μM) was found to be the most active inhibitor against A549 cells. While the selectivity index (SI) of compound 1 is 29, the SI of the reference drugs paclitaxel and sorafenib, used in this study, are 2.40 and 4.92, respectively. Among the hybrid compounds, 1 has the best docking scores against VEGFR1 (−11.744 kcal/mol), VEGFR2 (−12.407 kcal/mol) and EGFR (−10.359 kcal/mol). During MD simulations, compound 1 consistently exhibited strong hydrogen bond interactions with the active sites of VEGFR1 and 2, and these interactions were maintained for more than 90% of the simulation time. Additionally, the RMSD and RMSF values of the ligand–protein complexes exhibited high stability at their minimum levels around 1–2 Å. In conclusion, these findings suggest that compound 1 may be a potent and selective inhibitor candidate for lung cancer treatment and inhibition of VEGFR2, especially. [ABSTRACT FROM AUTHOR]

When treated with cycloalkylamines (pyrrolidine, piperidine, morpholine, and N-methylpiperazine), polyfluoro-containing benzoic and salicylic acid esters undergo chemoselective nucleophilic aromatic substitution of a fluorine atom in the para position to form 4-(N-cycloalkylamino)-substituted derivatives. The hydrolysis of the latter compounds with alkali in aqueous methanol affords the corresponding acids. Methyl 3,5-difluoro-2-hydroxy-4-(piperidin-1-yl)benzoate exhibits high antibacterial activity against the N. gonorrhoeae strain, which is twice higher than that of the drug spectinomycin. N-Cycloalkyl-substituted polyfluorobenzoic acids do not show analgesic activity. The effect of the esters is comparable with the activity of the drug diclofenac. The studied compounds have a lower acute toxicity compared to the reference drug. [ABSTRACT FROM AUTHOR]

[Display omitted] The new type of four-component tandem Knoevenagel–Michael reaction was found: isatins, barbituric acids, malononitrile and morpholine at ambient temperature and without catalysts selectively form new non-symmetrical ionic scaffold, namely, morpholin-4-ium 5-(3-dicyanomethyl-2-oxoindolin-3-yl)-1,3-dimethyl-2,6-dioxo-1,2,3,6-tetra-hydropyrimidin-4-olate derivatives, in 80-98% yields. Their structure was confirmed using 2D NMR such as 1H-1H COSY, 1H-13C HSQC, and 1H-13C HMBC correlation experiments. The products seem promising as they contain three different pharmacologically active heterocyclic rings. [ABSTRACT FROM AUTHOR]

This contribution describes a study on the reactivities of the complexes [{κP,κC-(i-Pr)2PO-Ar}Ni(μ-Br)]2, 1a–d (Ar: C6H4, a; 3-Cl-C6H3, b; 3-OMe-C6H3, c; 4-OMe-napthalenyl, d), with hydroxylamines in the presence of TEMPO˙ (TEMPO˙ = (2,2,6,6-tetramethylpiperidinyl-1-yl)oxyl). The results of this study showed that treating 1a–d with a mixture of Et2NOH and TEMPO˙ did not afford the desired oxidation-induced functionalization of the Ni-aryl moiety in 1a–d, giving instead the corresponding κO-TEMPOH adducts [{κP,κC-(i-Pr)2PO-Ar}Ni(Br)(κO-TEMPOH)], 3a–d (TEMPOH = N-hydroxy-2,2,6,6-tetramethylpiperidine). The TEMPOH moiety in these zwitterionic compounds 3 can be displaced by a large excess of acetonitrile (MeCN), 10 equiv. of morpholine, or 1–2 equivalents of imidazole. Although these reactions have given the authenticated products [{κP,κC-(i-Pr)2PO-C6H4}Ni(Br)(NCMe)], 4a, [{κP,κC-(i-Pr)2PO-C6H4}Ni(Br)(morpholine)], 5a, and [{κP,κC-(i-Pr)2PO-C6H4}Ni(imidazole)2]Br, 6a, a few other products were also detected by NMR, indicating that the observed reactivities are far more complex than simple substitution of the TEMPOH moiety. Similarly, treating 3a with AgOC(O)CF3 results in the isolation of [{κP,κC-(i-Pr)2PO-C6H4}Ni{OC(O)CF3}(κO-TEMPOH)], 7a, arising from the substitution of the bromo ligand, whereas spectroscopic evidence suggests further reactivity, possibly including displacement of TEMPOH and oxidative decomposition. [ABSTRACT FROM AUTHOR]

We report two methods for selective morpholinomethylation and formylation of C1 − H bonds in pyrrolo[1,2-a]quinoxalines. Reaction of pyrrolo[1,2-a]quinoxalines and morpholine using CuI catalyst, (bis(trifluoroacetoxy)iodo)benzene oxidant, and DMSO solvent yielded the morpholinomethylation products. Meanwhile, formylation of C1 − H bonds in pyrrolo[1,2-a]quinoxalines progressed in the presence of CuI catalyst, trifluoroacetic acid, and DMSO solvent. Compounds bearing halogen, methylsulfonyl, pyridine, and thiophene groups were isolated in moderate yields. [ABSTRACT FROM AUTHOR]

The chemical reaction of 2-(methylsulfinyl)naphtho[2,3-d]thiazole-4,9-dione (3) using different amines, including benzylamine (4a), morpholine (4b), thiomorpholine (4c), piperidine (4d), and 4-methylpiperazine (4e), produced corresponding new tricyclic naphtho[2,3-d]thiazole–4,9–dione compounds (5a–e) in moderate-to-good yields. The photophysical properties and antimicrobial activities of these compounds (5a–e) were then characterized. Owing to the extended π-conjugated system of naphtho[2,3-d]thiazole–4,9–dione skeleton and substituent effect, 5a–e showed fluorescence both in solution and in the solid state. The introduction of nitrogen-containing heterocycles at position 2 of the thiazole ring on naphtho[2,3-d]thiazole-4,9-dione led to large bathochromic shifts in solution, and 5b–e exhibited orange-red fluorescence with emission maxima of over 600 nm in highly polar solvents. Staphylococcus aureus (S. aureus) is a highly pathogenic bacterium, and infection with its antimicrobial-resistant pathogen methicillin-resistant S. aureus (MRSA) results in serious clinical problems. In this study, we also investigated the antimicrobial activities of 5a–e against S. aureus, MRSA, and S. epidermidis. Compounds 5c with thiomorpholine group and 5e with 4-methylpiperazine group showed potent antimicrobial activity against these bacteria. These results will lead to the development of new fluorescent dyes with antimicrobial activity in the future. [ABSTRACT FROM AUTHOR]

In this work, we synthesized a series of nine tetraalkylammonium salts derived from N‐methyl morpholine and assessed their antibacterial efficacy against Methicillin‐Resistant Staphylococcus aureus (MRSA). The investigated morpholinium cations differ by the length of one linear alkyl chain, which ranges from 1 to 18 carbon atoms. We found that compounds with alkyl chains in the n‐C12H25‐(n‐dodecyl) to C16H33‐(n‐hexadecyl) display the highest bactericidal effects, exhibiting Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) values of 3.9 μg/mL – surpassing the effectiveness of the commercial drug Linezolid. Conversely, compounds with shorter chains (<5 carbon atoms) are inactive against MRSA, establishing a clear structure‐activity relationship. Assays on A. salina reveal that short‐alkyl‐chain morpholinium derivatives, inactive against MRSA), are moderately toxic, while the strongest bactericides of our set demonstrate high or extreme toxicity to A. salina. Our findings underscore the potential of morpholine derivatives as a means to control Methicillin‐Resistant Staphylococcus aureus and pinpoint the need to develop safe applications for these compounds given their potential toxicity. [ABSTRACT FROM AUTHOR]

An important component of the pathogenicity of potentially pathogenic bacteria in humans is the urease enzyme. In order to avoid the detrimental impact of ureolytic bacterial infections, the inhibition of urease enzyme appears to be an appealing approach. Therefore, in the current study, morpholine-thiophene hybrid thiosemicarbazone derivatives (5a-i) were designed, synthesized and characterized through FTIR, 1H NMR, 13C NMR spectroscopy and mass spectrometry. A range of substituents including electron-rich, electron- deficient and inductively electron-withdrawing groups on the thiophene ring was successfully tolerated. The synthesized derivatives were evaluated in vitro for their potential to inhibit urease enzyme using the indophenol method. The majority of compounds were noticeably more potent than the conventional inhibitor, thiourea. The lead inhibitor, 2-(1-(5-chlorothiophen-2-yl)ethylidene)- N-(2-morpholinoethyl)hydrazinecarbothioamide (5g) inhibited the urease in an uncompetitive manner with an IC50 value of 3.80 ± 1.9 μM. The findings of the docking studies demonstrated that compound 5g has a strong affinity for the urease active site. Significant docking scores and efficient binding free energies were displayed by the lead inhibitor. Finally, the ADME properties of lead inhibitor (5g) suggested the druglikeness behavior with zero violation. [ABSTRACT FROM AUTHOR]

A crude morpholine enamine of acetone treated with Lawesson's reagent unexpectedly yielded a six-membered thiaphosphinane-4-one. This compound is the first example of a new class of heterocycles. It has been proven that it is formed from 4-methyl-2-morpholino-1,3-pentadiene which is usually present in crude morpholine enamine batches. A mechanism of this regioselective reaction was postulated and a characteristic chair-like conformation of the product was examined in detail. Additionally, some unusual primary fragmentations of the product with the loss of H2S and isobutylene were observed for positive and negative ESI ionization mode, respectively. [ABSTRACT FROM AUTHOR]

Cancers present a significant medical problem despite the development of medical and pharmaceutical sciences leading to a search for further therapeutic approaches. One such approach could involve the use of curcumin or its derivatives. Curcumin reveals interesting antineoplastic effects that could help in the treatment of cancer diseases. However, this natural product possesses some limitations which prevent its application in medicine. Among its limitations, it is characterized by poor water solubility, low stability, and unsatisfactory bioavailability. Aiming to improve the pharmacokinetic properties and enhance the biological effects of curcumin, a series of 30 chemical compounds inspired by its structure was synthesized and characterized. New compounds were subjected to a preliminary MTT viability assessment of 5637 and SCaBER bladder cancer cell lines. Some derivatives revealed the cytotoxic activities already at the concentration of 1 µM. The most active compounds showed no significant acute toxicity in the Microtox test. Intracellular uptake on the basis of the fluorescent properties of the new compounds was analyzed. It was also found that the presence of the morpholine group in the structure improved the biological activity of studied curcumin derivatives. As selected compounds could be considered potential drug candidates, further studies are necessary towards recognition of the exact mechanism of cellular action, the in vivo stability, and toxicity. [ABSTRACT FROM AUTHOR]

In quest of generating a diverse array of potential cytotoxic candidates through molecular hybridization approach, herein we have designed a library of forty‐one morpholine‐functionalized aurones 7(a–ao), each with a distinct substitution pattern. These aurones were obtained by reacting 6‐hydroxyaurones, with 4‐(2‐chloroethyl)morpholine hydrochloride, characterized by various spectroscopic techniques including single crystal XRD (7b) and in‐vitro screened for their antiproliferative potential against human gastric adenocarcinoma (AGS) cells. Most of the synthesized compounds have exhibited excellent cytotoxic results. Twenty analogs were found to have cytotoxic potential better than the reference drug Leucovorin and analog 7j emerged as the most potent with IC50=5.98 μM nearly one fifth to the standard drug Leucovorin (IC50=30.8 μM). This library, consisting of twenty three novel and eighteen reported morpholine‐functionalized aurones, bearing diverse substitution pattern, further helped in making a concrete structure‐activity relationship for antiproliferative potential. Additionally, in‐silico molecular docking, Hirshfeld surface analysis and two dimensional fingerprint plots were also studied to understand the molecular interactions and various structural aspects. Further computational investigations of these compounds were conducted using the DFT/B3LYP method, for the determination of HOMO and LUMO energy values as well as the calculation of chemical softness, hardness, electronegativity and electrophilic index etc. [ABSTRACT FROM AUTHOR]

Herein, the chemical synthesis of new thiazole-based benzenesulfonamide-linked morpholine 4a,b–7via late-stage thiazolation of the corresponding thiosemicarbazone 3 is reported. The skeletal formulas of the new compounds were confirmed via instrumental analysis (FT-IR, NMR, and EI-MS). Their structural geometry optimization and the related quantum chemical descriptors were predicted via DFT-B3LYP/6-31G(d) calculations. Their antimicrobial screening demonstrated that all the tested compounds except 4a and b showed antibacterial efficacy against multidrug-resistant Klebsiella pneumoniae with an inhibition zone ranging from 10 to 15 mm. Compound 7, which bears a 4-thiazolone moiety, is the most potent towards K. pneumoniae with an inhibition zone diameter (IZD) of 15 mm and is the sole molecule that exhibited broad-spectrum antimicrobial activity against all pathogenic bacterial and fungal strains with an IZD spanning from 11 to 18 mm. Enzymatic in vitro bioassays indicated that 7 is more potent towards DHFR (IC50 = 0.521 ± 0.027 μg mL−1) than DNA gyrase (IC50 = 6.14 ± 0.27 μg mL−1). The best action mode via molecular docking disclosed that 7 is interlocked into the cavity centre of DHFR with a lower binding fitness (−123.615 kcal mol−1) than DNA gyrase (−112.537 kcal mol−1), validating the experimental results and showing that the 4-thiazolone-linked methyl ester and sulfonamide units are responsible for the hydrogen bonding interactions. Accordingly, thiazole 7 could be a promising antimicrobial lead candidate. [ABSTRACT FROM AUTHOR]

Reactions between octa(2,6-fluorophenyl)porphyrazine and pyridine, 2-methylpyridine, morpholine, piperidine, butylamine, tert-butylamine, diethylamine, and triethylamine in a benzene medium have been studied. The acid–base reactions between the macroheterocycle and piperidine or butylamine are slow processes leading to the formation of kinetically stable proton-transfer complexes. The structures of these complexes have been optimized using CAM-B3LYP/cc-pVTZ. The changes in the reactivity of octa(2,6-fluorophenyl)porphyrazine are analyzed as a function of the steric structure and proton-acceptor power of the nitrogenous base. [ABSTRACT FROM AUTHOR]

A new type of the four-component tandem Knoevenagel—Michael reaction was discovered, which used arylaldehydes, N,N′-dimethylbarbituric acid, dimedone, and morpholine or piperidine in organic solvents or in water. The reaction proceeded under mild conditions at room temperature with the formation of a new substituted unsymmetrical polycyclic ionic scaffold in 83–98% yields. The structures of the reaction products were confirmed by X-ray diffraction analysis on the example of two compounds. The further oxidative cyclization of the Knoevenagel—Michael reaction products led to unsymmetrical substituted dihydrofurans spiro-annulated with N,N′-dimethylbarbituric acid. The structures of the synthesized compounds were confirmed by X-ray diffraction analysis. [ABSTRACT FROM AUTHOR]

A new nitronyl nitroxide ligand (L) has been obtained by the alkylation reaction of morpholine with 2-(chloromethyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazolyl-1-oxyl 3-oxide (NIT-CH2Cl). The reaction of L with [Ni(hfac)2(H2O)2] in hot n-heptane affords the mononuclear complex, [NiL(hfac)2] (1), characterized herein by single crystal X-ray diffraction, FTIR and UV-Vis spectroscopies. Within the nickel(II) complex, L acts as a chelating ligand, through one aminoxyl oxygen and through the morpholine nitrogen atom. The crystal structure of alkylation agent (NIT-CH2Cl) has been solved. [ABSTRACT FROM AUTHOR]

Choosing suitable wound dressings is crucial for effective wound healing. Spun scaffolds with bioactive molecule functionalization are gaining attention as a promising approach to expedite tissue repair and regeneration. Here, we present the synthesis of novel multifunctional quercetin with morpholine and pyridine functional motifs (QFM) embedded in silk fibroin (SF)-spun fibers (SF-QFM) for preclinical skin repair therapies. The verification of the novel QFM structural arrangement was characterized using ATR-FTIR, NMR, and ESI-MS spectroscopy analysis. Extensive characterization of the spun SF-QFM fibrous mats revealed their excellent antibacterial and antioxidant properties, biocompatibility, biodegradability, and remarkable mechanical and controlled drug release capabilities. SF-QFM mats were studied for drug release in pH 7.4 PBS over 72 h. The QFM-controlled release is mainly driven by diffusion and follows Fickian's law. Significant QFM release (40%) occurred within the first 6 h, with a total release of 79% at the end of 72 h, which is considered beneficial in effectively reducing bacterial load and helping expedite the healing process. Interestingly, the SF-QFM-spun mat demonstrated significantly improved NIH 3T3 cell proliferation and migration compared to the pure SF mat, as evidenced by the complete migration of NIH 3T3 cells within 24 h in the scratch assay. Furthermore, the in vivo outcome of SF-QFM was demonstrated by the regeneration of fresh fibroblasts and the realignment of collagen fibers deposition at 9 days post-operation in a preclinical rat full-thickness skin defect model. Our findings collectively indicate that the SF-QFM electrospun nanofiber scaffolds hold significant capability as a cost-effective and efficient bioactive spun architecture for use in wound healing applications. [ABSTRACT FROM AUTHOR]

–Objective: In this paper, a series of piperazine pyrimidines and morpholine pyrimidines have been synthesized effectively, and their biological activities have been evaluated. Methods: We examined the cytotoxicity tests of the compounds against two human tumor cells (HCT-116, HeLa), as well as one human normal cells (L02), in order to determine their anticancer activity. Results: The compound (IV) outperformed the others, and flow cytometry was used to further examine how it works against cancer. Additionally, the (IV) molecule showed strong anticancer efficacy but was marginally less effective in apoptosis assays than the control 5-FU. Discussion: The compound (IV) chemical treated HCT-116 cells and HeLa cells in the cell cycle research had a larger percentage of cells in the G1 phase. The induction of apoptosis by interfering with the cell cycle may be the anticancer mechanism of this substance. Additionally, molecular docking investigated potential interactions between the substances and the Topo II active site. Conclusions: The groundwork for the creation and structural modification of new pyrimidine medications is laid out in this study. [ABSTRACT FROM AUTHOR]

Objective: Synthesis of some new some new morpholine linked indole-1,2,3-triazole hybrids and evaluation of their anti-cancer activity. Methods: Cu (I) catalyzed azide-alkyne cycloaddition. MTT assay was used in anticancer activity. Autodock tools were used foe docking studies. Results and Discussion: All the sixteen compounds were screened against A549 (lung), MCF-7 (breast), and HeLa (cervical) and compared with nocodazole. In addition to this tubulin polymerization inhibition assay and docking studies were performed on some active compounds. Conclusions: Synthesized some new 1,2,3-triazole hybrids and screened them for anticancer activity, tubulin polymerization inhibition, and binding interaction with tubulin. Some of the compounds were found active. [ABSTRACT FROM AUTHOR]

Cobalt(II) and copper(II) complexes supported by 4‐(quinolin‐2‐ylmethyl)morpholine (L) were characterized, and their reactivity toward the ring‐opening polymerization (ROP) of rac‐lactide (rac‐LA) was studied. The use of [LMCl2]/LiOiPr and [LMCl2]/LiMe (M = Co, Cu) resulted in over 95% conversion within 10 min at 25 °C. The effect of the initiating group and geometry of the metal complexes steered the heterotactic enchainment of the resultant polylactide(PLA). The Co(II)/LiMe system represents the first example of the ROP of rac‐LA with high heterotactic enchainment (Pr = 0.92) with 98% conversion at 0 °C. [ABSTRACT FROM AUTHOR]

Abstract Nine morpholine-derived halogenated chalcone derivatives (MHC1-MHC9) were synthesized, and their inhibitory activity against monoamine oxidase (MAO) was evaluated. MHC5 showed the highest inhibitory activity against MAO-B with an IC50 value of 0.065 μM, followed by MHC7 (IC50 = 0.078 μM) and MHC6 (IC50 = 0.082 μM). The para-F substituent MHC4 was also potent (IC50 = 0.095 μM). The selectivity index values of all the compounds were high for MAO-B over MAO-A, and the values for MHC5 and MHC4 were 66.15 and 80.11, respectively. MHC5 and MHC4 were competitive MAO-B inhibitors with Ki values of 0.024 ± 0.00062 and 0.041 ± 0.0028 μM, respectively. In reversibility tests, the changes in residual activity before and after the dialysis of MHC5 and MHC4 were similar to those of safinamide, a reversible MAO-B reference inhibitor. Additionally, molecular docking and dynamic simulations predicted that the lead molecules MHC5 and MHC4 could strongly bind to the MAO-B active site with docking scores of –10.92 ± 0.08 and –10.64 ± 0.14 kcal/mol, respectively. Additionally, MHC4 and MHC5 exhibited favorable ADME features, including blood–brain barrier permeability. The experiments confirmed that MHC5 and MHC4 are reversible and potent selective inhibitors of MAO-B and are promising candidates for the treatment of neurodegenerative diseases (human health).

Here we report a metal‐free direct C−H trifluoromethylation of the imidazothiazoles 7(a–ad) using sodium triflouromethanesulfinate (Langlois' reagent) and tert‐butyl hydroperoxide (TBHP) as an oxidant. The control studies show that the protocol follows the radical reaction pathway and provides excellent yields of trifluoromethylated products 9(a–ad) with broad substrate scope and regioselective operation. Moreover, the newly synthesized compounds exhibit promising antimycobacterial activity. [ABSTRACT FROM AUTHOR]

This study presents a straightforward solution to the challenge of elucidating the structures of nitrogen containing compounds undergoing isomerization. When spectral line broadening occurs related to isomerization, be it prototropic tautomerism or bond rotations, this poses a significant obstacle to structural elucidation. By adding acids, we demonstrate a simple approach to overcome this issue and effectively sharpen NMR signals for acid stable prototropic tautomers as well as the conformational isomers containing a morpholine or piperazine ring. [ABSTRACT FROM AUTHOR]

Previously synthesized ethyl 2-benzamido-4-(1,4-benzodioxan-2-yl)thiophene-3-carboxylates were cyclized to 2-aryl-3-aminothieno[2,3-d]pyrimidin-4(1H)-ones by the action of hydrazine hydrate. The con-densation of ethyl 2-amino-4-(1,4-benzodioxan-2-yl)thiophene-3-carboxylate with chloroacetyl chloride gave the corresponding N-substituted 2-chloroacetamide which reacted with piperidine and morpholine to produce 2-aminoacetamides, and the latter were also subjected to cyclization with hydrazine hydrate to obtain 3-amino-thienopyrimidin-4-one derivatives. The synthesized compounds were tested for antihypoxic activity. [ABSTRACT FROM AUTHOR]

Heterocyclic‐based cationic surfactants with dodecyl tail group bridged to the head group either via aromatic ether [3‐(4‐dodecyloxybenzyl)‐1‐methyl‐imidazolium bromide (Ar‐I) and 4‐(4‐dodecyloxybenzyl)‐4‐methyl‐morpholinium bromide (Ar‐M)] or via aliphatic ether [3‐(2‐dodecyloxyethyl)‐1‐methyl imidazolium bromide (Al‐I) and 4‐(2‐dodecyloxyethyl)‐4‐methyl morpholinium bromide (Al‐M)] were synthesized and characterized using different spectral techniques. For the synthesis of Ar‐I and Ar‐M, 4‐hydroxybenzoic acid was esterified initially, followed by O‐alkylation, reduction, bromination and finally quaternization either with 1‐methylimidazole or with 4‐methylmorpholine. For the synthesis of aliphatic analogues (Al‐I and Al‐M), ethylene glycol was initially alkylated, followed by tosylation, bromination and quaternization either with 1‐methylimidazole or with 4‐methylmorpholine. Synthesized surfactants were evaluated for surface and self‐assembly properties. Impact of the presence or absence of phenyl ring bridging the polar head and nonpolar tail of the surfactant and also type of heterocyclic moiety in the head group region on micellization and surface properties such as wetting, foaming and emulsification was studied. Surfactants with the bridged aromatic ether moiety were observed to display lower critical micelle concentration than those with the bridged aliphatic ether moiety irrespective of type of heterocyclic molecule in the head group region. Foam volume and stability of the aromatic ether‐bridged surfactant were observed to be superior to their corresponding aliphatic analogs. Similar trend was observed in stabilizing the emulsion. However, aromatic ether‐bridged surfactant depicted poor wetting ability compared to their aliphatic analog. Aliphatic ether bridged surfactant showed higher aggregation number compared to their aromatic counterparts, but depicted similar micellar core polarity. [ABSTRACT FROM AUTHOR]

Herein described the synthesis and antiviral evaluation of a novel series of morpholine and thio‐morpholine coupled imidazo[2,1‐b]thiazoles. The three‐step reaction sequence involving the condensation of 1,3‐dichloroacetone with thiourea followed by coupling with morpholine and thiomorpholine and finally cyclization with substituted α‐bromoacetophenones yielded the desired imidazothiazoles 7(a–l). Screening of all the new compounds for their in vitro antiviral activity against influenza virus A/Puerto Rico/8/34 (H1N1) in MDCK cells, resulted in two potent analogs, 7d (IC50: 1.1 μM, C50: >300 μM, SI = 273) and 7e (IC50: 2.0 μM, C50: >300 μM, SI = 150), with a favorable toxicity profile and are the best anti‐influenza hit analogs for further structural optimization. [ABSTRACT FROM AUTHOR]

The title compound, [CdBr2(C6H14N2O)], was synthesized upon complexation of 4-(2-aminoethyl)morpholine and cadmium(II) bromide tetrahydrate at 303 K. It crystallizes as a centrosymmetric dimer, with one cadmium atom, two bromine atoms and one N,N'-bidentate 4-(2-aminoethyl)morpholine ligand in the asymmetric unit. The metal atom is six-coordinated and has a distorted octahedral geometry. In the crystal, O…Cd interactions link the dimers into a polymeric double chain and intermolecular C--H…O hydrogen bonds form R2/2(6) ring motifs. Further C--H…Br and N--H…Br hydrogen bonds link the components into a three-dimensional network. As the N--H…Br hydrogen bonds are shorter than the C--H…Br interactions, they have a larger effect on the packing. A Hirshfeld surface analysis reveals that the largest contributions to the packing are from H…H (46.1%) and Br…H/H…Br (38.9%) interactions with smaller contributions from the O- - -H/H- - -O (4.7%), Br…Cd/Cd…Br (4.4%), O…Cd/Cd…O (3.5%), Br…Br (1.1%), Cd…H/H…Cd (0.9%), Br…O/O…Br (0.3%) and O…N/N…O (0.1%) contacts. [ABSTRACT FROM AUTHOR]

4-(4-nitrophenyl)thiomorpholine, the title compound, has been used as a precursor for the corresponding 4-thiomorpholinoaniline, which is a useful building block in medicinal chemistry. The crystal and molecular structures of the title compound, however, have not been described thus far. We synthesized the title compound by means of a nucleophilic aromatic substitution reaction of 4-fluoronitrobenzene and thiomorpholine and structurally characterized it by X-ray crystallography, DFT calculations, and Hirshfeld surface analysis. In the crystal, the molecule exhibits an approximately CS-symmetric structure, with the nitrogen-bound 4-nitrophenyl group in a quasi axial position on the six-membered thiomorpholine ring in a low-energy chair conformation. The solid-state structure of the title compound is markedly different from that of its morpholine analogue. This can be ascribed to the formation of centrosymmetric dimers through intermolecular C–H···O weak hydrogen bonds involving the methylene groups adjacent to the sulfur atom and face-to-face aromatic stacking. [ABSTRACT FROM AUTHOR]

During the COVID‐19 pandemic, the use of polypropylene fleece‐based personal protection equipment (PPE) increased significantly to over ten million tons. Typically, most PPEs are discarded after a single use, to prevent self‐infection of users and spread of infectious agents. However, in order to minimize plastic waste without compromising the protective properties of PPE, it is crucial to explore new reusable or longer‐lived materials. Here, a visible light‐activatable antimicrobial photodynamic dye coating for PPEs is presented. In this context, coating with thiomorpholino‐methylene blue (TMB), derived from methylene blue by introducing two thiomorpholine units, is found to show high antibacterial activity. TMB is integrated into rotary printing suspension, a commercial nitrocellulose‐based printing matrix. The concentration of TMB in adhesive is optimized, and found that 5% TMB is suitable for coating PPE, for reducing the number of Gram‐positive and ‐negative bacteria by 99.99% after 6 h of white light irradiation. Bacterial filtration efficiency and breathability tested according to EN 14683, confirmed that TMB coating does not affect the filter performance. Thus, this antimicrobial photodynamic dye coating technique offers a promising solution for a safer and extended use of PPE, and reduction of plastic waste generated by PPEs. [ABSTRACT FROM AUTHOR]

Morpholine motifs have been used extensively as targeting moieties for lysosomes, primarily in fluorescence imaging agents. Traditionally these imaging agents are based on organic molecules which have several shortcomings including small Stokes shifts, short emission lifetimes, and susceptibility to photobleaching. To explore alternative lysosome targeting imaging agents we have used a rhenium based phosphorescent platform which has been previously demonstrated to have an improved Stokes shift, a long lifetime emission, and is highly photostable. Rhenium complexes containing morpholine substituted ligands were designed to accumulate in acidic compartments. Two of the three complexes prepared exhibited bright emission in cells, when incubated at low concentrations (20 μM) and were non-toxic at concentrations as high as 100 μM, making them suitable for live cell imaging. We show that the rhenium complexes are amenable to chemical modification and that the morpholine targeted derivatives can be used for live cell confocal fluorescence imaging of endosomes–lysosomes. [ABSTRACT FROM AUTHOR]

The green synthesis approach employs ultrasound waves as an effective and environmentally friendly strategy to catalyze chemical reactions. Within this framework, carbonitrile-bearing tetrahydropyrimidine derivatives were successfully synthesized. This involved the reaction of malononitrile, urea or thiourea, and variously substituted aldehydes in the presence of morpholine as a catalyst, conducted in aqueous conditions under ultrasonic irradiation. Notably, this method resulted in elevated reaction yields and significantly reduced reaction times when compared to conventional approaches. The synthesized compounds underwent comprehensive characterization using various spectroscopic techniques, including UV-Vis, 1H NMR, 13C NMR, and mass spectrometry. This innovative process aligns with the principles of green chemistry, emphasizing efficiency, sustainability, and the reduction of environmental impact in chemical synthesis. [ABSTRACT FROM AUTHOR]

A new strategy to access α‐functionalized alicyclic amines via their corresponding imine‐BF3 complexes is reported. Isolable imine‐BF3 complexes, readily prepared via dehydrohalogenation of N‐bromoamines in a base‐promoted/18‐crown‐6 catalyzed process followed by addition of boron trifluoride etherate, undergo reactions with a wide range of organometallic nucleophiles to afford α‐functionalized azacycles. Organozinc and organomagnesium nucleophiles add at ambient temperatures, obviating the need for cryogenic conditions. In situ preparation of imine‐BF3 complexes provides access to α‐functionalized morpholines and piperazines directly from their parent amines in a single operation. α‐Functionalized morpholines can be elaborated further, for instance by installing a second substituent in the α′‐position. [ABSTRACT FROM AUTHOR]

This article discusses the development of fluorescent probes for imaging lysosomes, which are organelles involved in maintaining cellular homeostasis and recycling. The researchers investigated the effects of different morpholine modifications on the imaging ability of the probes. They found that modification at the phenyl site improved fluorescence behavior and lysosome specificity. The probes showed good biocompatibility and were able to effectively image lysosomes in living cells. The study also explored the role of lysosomes in lipophagy, a process involved in lipid degradation. Overall, this research provides valuable insights for the design of lysosome-targeting probes and their potential applications in studying lysosome-related diseases. [Extracted from the article]

Oleanolic and glycyrrhetic acids alkyne derivatives were synthesized as a result of propargylation of the indole NH‐group condensed with the triterpene A‐ring, the following aminomethylation led to a series of Mannich bases. The synthesized compounds were tested for their potential inhibition of influenza A/PuertoRico/8/34 (H1N1) virus in Madin‐Darby canine kidney (MDCK) cell culture and SARS‐CoV‐2 pseudovirus in baby hamster kidney‐21‐human angiotensin‐converting enzyme 2 (BHK‐21‐hACE2) cells. Mannich bases of oleanolic and glycyrrhetic acids N‐propargylated indoles 7, 8, and 12 were the most efficacious against influenza virus A with IC50 7–10 μM together with a low toxicity (CC50 > 145 μM) and high selectivity index SI value 20. Indolo‐oleanolic acid morpholine amide Mannich base holding N‐methylpiperazine moiety 9 showed anti‐SARS‐CoV‐2 pseudovirus activity with EC50 value of 14.8 μM. Molecular docking and dynamics modeling investigated the binding mode of the compounds 7 and 12 into the binding pocket of influenza A virus M2 protein and compound 9 into the RBD domain of SARS‐CoV‐2 spike glycoprotein. [ABSTRACT FROM AUTHOR]

In search of better antibacterial and anticancer agents, this report presents a series of novel N-[3-fluoro-4-(morpholin-4-yl)aryl]thiazol-2-amine derivatives (6a–6l) that were synthesized and evaluated for their antibacterial and anticancer activity in vitro. Antibacterial activity against three G+ bacterial strains and anticancer activity against MCF-7 and A-549 was evaluated. Among all the tested compounds, 6i and 6j exhibited potent antibacterial activity against Staphylococcus aureus and Staphylococcus epidermidis bacterial strains. Biofilm profiles for the potent compounds and it was observed from the results that the active derivatives 6i and 6j were not only potent antibacterial agents but also efficient inhibitors of S. aureus and S. epidermidis biofilm growth. Compared to the standard drug, erlotinib, the anticancer activity screening results of 6h and 6k demonstrated high cytotoxic activity against the A-549 cancer cell line. Later, the results of the inhibitory assay of potent compounds 6h and 6k against the tyrosine kinase EGFR revealed that compound 6k showed ≈1.5 fold potency of the reference drug erlotinib. Finally, compounds 6h, 6i, 6j, and 6k did not show AMES toxicity and followed the rules of Lipinski, Ghose, Veber, Egan, and Muegge rules without any deviation. [ABSTRACT FROM AUTHOR]