Search

Reaction of 9-fluorene propargylic alcohols and substituted-2-hydrazinopyridine using BF3·OEt2 as a Lewis acid catalyst afforded 9-fluorenlidene appended 2-hydrazinopyridine imine derivatives has been developed. The scope of the reaction is demonstrated by selecting a range of fluorene propargylic alcohols and substituted 2-hydrazinopyridine imines. All the synthesized molecules were characterized using various spectroscopic and analytical techniques including 1H NMR,13C NMR, and Mass spectrometry. A plausible reaction mechanism for forming title compounds via propargylic allenyl carbocation is postulated. The synthetic utility of products thus formed is demonstrated by utilizing Suzuki coupling. [ABSTRACT FROM AUTHOR]

An efficient strategy for rapid assembly of the complex substituted cyclohexene core that is present in several cyclic imine marine toxins is presented. Several of these toxins, including pinnatoxin A and recently discovered portimine A, have been the focus of much attention due to their fascinating biological activities. We demonstrate that the substituted cyclohexene-diene motif, which is a challenging feature to access synthetically, can be prepared through a stepwise Ireland–Claisen rearrangement/enyne metathesis procedure beginning from chiral esters. This approach enables a divergent strategy that can be implemented in syntheses of cyclic imines or derivatives thereof. [ABSTRACT FROM AUTHOR]

We report here a method to make a branched and partially ethoxylated polyethyleneimine derivative directly from ethanolamine. The polymerization reaction is catalysed by a pincer complex of Earth-abundant metal, manganese, and produces water as the only byproduct. Industrial processes to produce polyethyleneimines involve the transformation of ethanolamine to a highly toxic chemical, aziridine, by an energy-intensive/waste-generating process followed by the ring-opening polymerization of aziridine. The reported method bypasses the need to produce a highly toxic intermediate and presents advantages over the current state-of-the-art. We propose that the polymerization process follows a hydrogen borrowing pathway that involves (a) dehydrogenation of ethanolamine to form 2-aminoacetaldehyde, (b) dehydrative coupling of 2-aminoacetaldehyde with ethanolamine to form an imine derivative, and (c) subsequent hydrogenation of imine derivative to form alkylated amines. The industrial process for the synthesis of branched polyethylenimine (PEI) and polyethylenimine ethoxylated (PEIE) uses highly toxic and mutagenic chemicals. Here the authors report a method to make a branched and partially ethoxylated polyethyleneimine derivative directly from ethanolamine using a pincer complex of Earth-abundant manganese, and producing water as the only byproduct. [ABSTRACT FROM AUTHOR]

Developing highly active materials that efficiently utilize solar spectra is crucial for photocatalysis, but still remains a challenge. Here, we report a new donor-acceptor (D-A) covalent organic framework (COF) with a wide absorption range from 200 nm to 900 nm (ultraviolet-visible-near infrared light). We find that the thiophene functional group is accurately introduced into the electron acceptor units of TpDPP-Py (TpDPP: 5,5'-(2,5-bis(2-ethylhexyl)−3,6-dioxo-2,3,5,6-tetrahydropyrrolo [3,4-c]pyrrole-1,4-diyl)bis(thiophene-2-carbaldehyde), Py: 1,3,6,8-tetrakis(4-aminophenyl)pyrene) COFs not only significantly extends its spectral absorption capacity but also endows them with two-photon and three-photon absorption effects, greatly enhancing the utilization rate of sunlight. The selective coupling of benzylamine as the target reactant is used to assess the photocatalytic activity of TpDPP-Py COFs, showing high photocatalytic conversion of 99% and selectivity of 98% in 20 min. Additionally, the TpDPP-Py COFs also exhibit the universality of photocatalytic selective coupling of other imine derivatives with ~100% conversion efficiency. Overall, this work brings a significant strategy for developing COFs with a wide absorption range to enhance photocatalytic activity. Creating highly active materials that effectively harness solar spectra is essential for photocatalysis, though challenging. Here the authors introduce a novel donor-acceptor covalent organic framework with a broad absorption range of 200 nm to 900 nm, achieving efficient artificial photocatalytic amine coupling. [ABSTRACT FROM AUTHOR]

This study presents the synthesis of a novel series of imine derivatives derived from imidazo[1,2‐a]pyridine as potential therapeutic agents. The imines were obtained by condensing 2‐(4‐bromophenyl)‐6‐chloroimidazo[1,2‐a]pyridine‐3‐carbaldehyde with primary amines, leading to high‐purity products that were characterized using various spectroscopic techniques. The compounds demonstrated promising in vitro antimicrobial activity against various bacteria, including Staphylococcus aureus and Escherichia coli, as well as fungi, such as Candida albicans, Saccharomyces cerevisiae, and Aspergillus brasiliensis. Furthermore, the antioxidant properties of the imine derivatives were evaluated using DPPH and ABTS techniques, and the IC50 values measured revealed their ability to scavenge free radicals. Overall, this study provides a valuable contribution to the field of pharmacology by synthesizing a new series of imine derivatives with significant potential as new therapeutic agents, exhibiting both antimicrobial and antioxidant properties. [ABSTRACT FROM AUTHOR]

A novel aromatic imine derivative, 2′-(1,4-phenylene)bis[4-[(4-methoxyphenyl)methylene]-5(4H)-oxazolone] (PBMBO), was designed and synthesized as a yellow colorant additive for green color filters used in image sensors. The optical and thermal properties of the newly developed material were evaluated both in solution and within color filter film conditions. PBMBO demonstrated a molar extinction coefficient of 2.24 × 104 L/mol·cm in solution, surpassing that of the commercially employed yellow colorant MBIQO by a factor of 1.82. Color resist (CR) films incorporating PBMBO exhibited outstanding optical characteristics, displaying 0.03% transmittance at 435 nm, 99.3% transmittance at 530 nm, and a sharp slope within the 400 to 550 nm range. The decomposition temperature of PBMBO was 303 °C, indicating relatively superior thermal stability compared to MBIQO. Consequently, PBMBO emerges as a highly promising candidate for a yellow colorant additive in imaging sensor color filters, owing to its exceptional optical and thermal stability. Its potential applications are anticipated to extend across various fields of organic semiconductors. [ABSTRACT FROM AUTHOR]

Pseudoproline derivatives such as Thr(ΨPro)-OH are commonly used in peptide synthesis to reduce the likelihood of peptide aggregation and to prevent aspartimide (Asi) formation during the synthesis process. In this study, we investigate notable by-products such as aspartimide formation and an imine derivative of the Thr(ΨPro) moiety observed in flow peptide chemistry synthesis. To gain insight into the formation of these unexpected by-products, we design a series of experiments. Furthermore, we demonstrate the oxazolidine character of the pseudoproline moiety and provide plausible mechanisms for the two-way ring opening of oxazolidine leading to these by-products. In addition, we present evidence that Asi formation appears to be catalyzed by the presence of the pseudoproline moiety. These observed side reactions are attributed to elevated temperature and pressure; therefore, caution is advised when using ΨPro derivatives under such harsh conditions. In addition, we propose a solution whereby thermodynamically controlled Asi formation can be kinetically prevented. [ABSTRACT FROM AUTHOR]

In this work, reactions between 6,7-dichloropyrido[1,2-a]benzimidazole-8,9-diones with different benzohydrazides were studied. Nucleophilic substitution at C(6) was followed by isomerization and led to α-hydroxy-p-quinone imine derivatives. Synthesized compounds represent a combination of several structural motifs: a benzimidazole core fused with α-hydroxy-p-quinone imine, which contains a benzamide fragment. X-ray crystallography analysis revealed the formation of dimers linked through OH···O interactions and stabilization of the imine form by strong intramolecular NH···N hydrogen bonds. The protonation/deprotonation processes were investigated in a solution using UV–Vis spectroscopy and a 1H NMR titration experiment. Additionally, the electrochemical properties of 6,7-dichloropyrido[1,2-a]benzimidazole-8,9-dione and its α-hydroxy-p-quinone imine derivative as cathode materials were investigated in acidic and neutral environments using cyclic voltammetry measurements. Cathode material based on 6,7-dichloropyrido[1,2-a]benzimidazole-8,9-dione could act as a potentially effective active electrode in aqueous electrolyte batteries; however, further optimization is required. [ABSTRACT FROM AUTHOR]

Imine derivatives are widely used in medicine for the treatment of several diseases causing human infections; we examined Schiff's bases derivatives: 2-[(3-methylphenyl) azomethine] phenol (L1), 2-[(3-chlorophenyl) azomethine] phenol (L2) and 2-[(3-nitrophenyl) azomethine] phenol (L3) against three human pathogenic bacterial strains according to the disk diffusion test. In addition, to revealing the importances of the in silico study of these derivatives, in particular the molecular docking which is based on the protein structures: the main protease 3CL of SARS-CoV-2 and the aminopeptidase of the M1 family. Also, a molecular dynamics simulation was performed to examine the structural stability of the best docked conformation. The evaluation of the global reactivity parameters of the molecular system of Schiff base derivatives was applied by the DFT method with the hybrid functional (B3LYP)/6-31G (d) basis set. The results of the antibacterial activity showed a strong activity in the presence of the L3 ligand against Escherichia coli (ATCC 25922) with a diameter inhibition zone equal to 11 ± 0.61 mm. Molecular docking shows that the L3 ligand formed with protein targets more stable complexes by predicting interesting interactions: hydrogen, hydrophobic and electrostatic bonds with the residues of these targets 3CLpro and PfA-M1. Further, molecular dynamics simulations confirm a strong energy contribution with these interactions. Therefore, suggesting that our ligands could contribute to the development of anti-coronavirus-2 and anti-malarial drug properties. [ABSTRACT FROM AUTHOR]

Umpolung is an old and important concept in organic chemistry, which significantly expands the chemical space and provides unique structures. While, previous research focused on carbonyls or imine derivatives, the umpolung reactivity of polarized C–C σ-bonds still needs to explore. Herein, we report an umpolung reaction of bicyclo[1.1.0]butanes (BCBs) with electron-deficient alkenes to construct the C(sp3)-C(sp3) bond at the electrophilic position of C–C σ-bonds in BCBs without any transition-metal catalysis. Specifically, this transformation relies on the strain-release driven bridging σ-bonds in bicyclo[1.1.0]butanes (BCBs), which are emerged as ene components, providing an efficient and straightforward synthesis route of various functionalized cyclobutenes and conjugated dienes, respectively. The synthetic utilities of this protocol are performed by several transformations. Preliminary mechanistic studies including density functional theory (DFT) calculation support the concerted Alder-ene type process of C–C σ-bond cleavage with hydrogen transfer. This work extends the umpolung reaction to C–C σ-bonds and provides high-value structural motifs. Umpolung reactions typically focus on carbonyls or imine derivatives. Here, the authors report the umpolung reaction of C–C σ-bonds in bicyclo[1.1.0]butanes (BCBs) with electrophilic alkenes, yielding various cyclobutenes or conjugated dienes. [ABSTRACT FROM AUTHOR]

A simple imine derivative based sensor (IDP) has been synthesized and characterized by 1 H NMR, 13 C NMR and mass spectral techniques. IDP is more capable of detecting perfluorooctanoic acid (PFOA) in a selective and sensitive manner. The PFOA as a biomarker interacts with IDP and shows "TURN-ON" response by colorimetric and fluorimetric method. Under optimized experimental observations, the selective determination of PFOA using IDP among other competitors as biomolecules has been noticed. The detection limit is 0.31 × 10− 8 mol/L. The practical applications of the IDP is effectively evaluated in human biofluids and water samples. [ABSTRACT FROM AUTHOR]

New macrocyclic Schiff bases, lower rim disubstituted imine derivatives of thia- and calix[4]arenes 7 and 8 adopted in a cone stereoisomeric conformation, bearing two tert-butyl substituents grafted to iminophenol coordinating sites, and containing a spacer composed of two methylene bridges were synthesized. The prepared compounds were characterized by a complex of physicochemical methods in solution (1H/13C NMR spectroscopy, MALDI TOF mass spectrometry) and in the crystalline phase (IR spectroscopy, single-crystal X-ray diffraction (XRD)). In crystals calix[4]arene 7 forms a solvate in which acetonitrile or methanol molecules are included into the macrocycle cavity, whereas the crystals of thiacalix[4]arene 8 contain no solvent molecules. The difference in the conformational behavior of the macrocyclic platform was evidenced when comparing the crystal structures of calix[4]arene 7 and thiacalix[4]arene 8. The stoichiometry and the logarithm and stability constant values of the corresponding complexes of the synthesized macrocyclic Schiff bases with 3d-metal cations (CoII, NiII) in solution were determined using spectrophotometry titration. When interacting with CoII cations, compound 7 forms complexes with stoichiometry Lig: M = 1: 1 and 1: 2 (Lig is ligand, and M is metal). In the case of compound 8, complexes with the stoichiometry Lig: M = 1: 4, as well as 1: 2, are observed, which presumably indicates the involvement of "soft" sulfur atoms in the interaction with the metal cations. The replacement of CoII cations by NiII resulted in the formation in the solution of complexes with the stoichiometry Lig: M = 2: 1, 1: 1 and Lig: M = 1: 1, 1: 2 for compounds 7 and 8, respectively. [ABSTRACT FROM AUTHOR]

Inflammation is one of the pertinent responses of the body, depending mainly on the process and factors involved in combating the oxidative species produced either by any infection or failure of the antioxidant pathways. In search of new compounds to exhibit antioxidant and anti-inflammatory activity here, we have successfully reported the synthesis of three novel compounds of Piperidin-4-one skeleton by adopting simple and convenient methods. Compound 1, (3, 3-dimethyl-2, 6-bis(3,4,5-trimethoxyphenyl) piperidin-4-one) was synthesized by one-pot Mannich condensation reaction having good yield (88 %). Furthermore in the next step highly functionalized imine derivatives, Compound 2 (3,3-dimethyl-2,6-bis (3,4,5-trimethoxyphenyl) piperidine-4-one) hydrazine carbothioamide) and Compound 3 (3,3-dimethyl-2,6-bis(3,4,5-trimethoxyphenyl) piperidin-4-one oxime) were prepared by the condensation reaction with thiosemicarbazide and hydroxylamine hydrochloride with compound 1, respectively. The structure of the compounds has been deduced by the combined use of modern spectroscopic and single crystal x-ray diffraction (XRD) techniques. in-silico ADMET studies predict pharmacokinetic properties and showed that compounds are non toxic on vital organs. The optimized geometry and reactivity parameters of compounds were further calculated based on the B3LYP/6-31G (d, p) density functional theory (DFT). The negative values of chemical potential follow the trend as 2 (−0.2101) > 3 (−0.2198) > 1(-0.2233) signifies that all compounds are reactive in nature as evident from in-vitro antioxidant and anti-inflammatory response were determined by using the DDPH assay and protein denaturation methods respectively. Compounds possess good radical scavenging activity having IC 50 values 30.392 μM (2), 37.802 (1) μM, and 72.285 (3) μM, and anti-inflammatory response in same manner indicating that 2 (71.3 %) is more active than compound 1 (43.5 %) and 3 (39.3 %) marking them as a potential antioxidant and anti-inflammatory agents.

In this article, a Schiff base derivative has been prepared using 2‐hydroxy‐1,4‐naphthoquinone and 3‐amino‐1,2,4‐triazole, and consecutively, four metal complexes (Co(II), Ni(II), Cu(II) and Zn(II)) have been synthesized using this Schiff base derivative as precursor ligand. Characterization of the synthesized compounds are done by employing spectral techniques such as UV–vis, infrared (IR), nuclear magnetic resonance (NMR), mass and electron paramagnetic resonance (EPR). All these methods establish the existence of imine group and the octahedral geometry of the complexes. The synthesized complexes are evaluated for their DNA binding properties that confirm that the binding mode is intercalation. The bioactive ligand and its complexes also exhibit pronounced pharmacological activities such as antioxidant and antimicrobial activities against bacteria such as Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Salmonella typhi; fungi, namely, Aspergillus niger, Aspergillus flavus, Candida albicans and Rhizoctonia bataticola. Moreover, the compounds are examined for their density functional theory (DFT) studies using Gaussian 09 programme. Various reactivity descriptors are calculated based on the highest occupied molecular orbital–lowest unoccupied molecular orbital (HOMO‐LUMO) energies. Molecular docking is conducted with two different receptors 1BNA and 1HD2 proteins to get a wide knowledge on the in vitro biological examination and also the interaction of the compounds with different proteins. [ABSTRACT FROM AUTHOR]

Nitrile imine derivative 3 added regioselectively to α-(benzothiazol-2-yl)cinnamonitrile derivatives 1a–c to afford 5-(benzothiazol-2-yl)-5-cyano-4,5-dihydro-1H-pyrazole derivatives 4a–c. Compound 4a underwent thermal elimination of hydrogen cyanide in sodium ethoxide solution to give the pyrazole derivative 6. The isoxazole derivative 10 was synthesized by reacting nitrile oxide 8 with cinnamonitrile derivative 1d. The structures of the synthesized compounds were characterized by FT-IR, NMR, and MS spectroscopic techniques. The reaction mechanism was studied via density functional theory (DFT) quantum chemical calculations at the B3LYP/6-31G (d) level of theory. [ABSTRACT FROM AUTHOR]

Leishmaniasis is considered one of the most untreated tropical diseases in the world. In this study, we investigated the in vitro leishmanicidal activity and cytotoxicity of various isolated lichen substances, including atranorin (1), usnic acid (2), gyrophoric acid (3), salazinic acid (4), galbinic acid (5), and parietin (6), and some semi-synthetic imine derivatives of usnic acid (7, 8, 9) and atranorin (10, 11, 12, 13). Imine condensation reactions with hydrazine and several amines were assisted by microwave heating, an efficient and eco-friendly energy source. The most interesting result was obtained for compound 2, which has high leishmanicidal activity but also high cytotoxicity. This cytotoxicity was mitigated in its derivative, 9, with better selectivity and high antileishmanic activity. This result may indicate that the usnic acid derivative (9) obtained using condensation with two cyclohexylamine groups is a promising lead compound for the discovery of new semisynthetic antiparasitic drugs. [ABSTRACT FROM AUTHOR]

A series of hydrazide‐hydrazone imine derivative compounds (3a–k) were synthesized and their structures characterized using FTIR, 1H, and 13C (NMR) spectroscopic methods. In addition, molecular structures of compounds 3a, 3d, and 3g were elucidated by X‐ray diffraction technique. In vitro inhibition activities of hydrazide‐hydrazone imine derivatives against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were investigated. Compound 3i (IC50 = 2.01 μM) exhibited the best inhibitory activity against AChE, comparable to the control Galantamine (IC50 = 2.60 μM). Against BChE, compound 3h (IC50 = 2.83 μM) showed the best inhibitory property which is higher control Galantamine (IC50 = 3.70 μM). The Ki values of compound 3i (Ki = 0.63 μM) and compound 3h (Ki = 0.94 μM) that have the strongest inhibitory potential were determined against AChE and BChE, respectively. According to the docking result, the most stable conformation of AChE and compound 3i showed that it has a binding affinity of −10.82 kcal/moL. The binding affinity of the most stable conformation formed by BChE and compound 3h is −8.60 kcal/moL. Finally, in silico results and pharmacokinetic parameters of ADME showed that these compounds have good oral bioavailability properties. [ABSTRACT FROM AUTHOR]

Graphene is one of the amazing present encroachments in current research area of science and one of the utmost fascinating materials for relevance in cutting-edge research. Herein, we designed lemon-derived heteroatoms-doped graphene quantum dots (S, N-GQDs) based photocatalyst for the first time. For the integrating reactions of amines in aerobic conditions under solar light by S, N-GQDs photocatalyst exhibit utmost higher photocatalytic activity than simple oxygen-doped graphene quantum dots (O-GQDs) due to slow recombination charges. The mechanisms accountable for the drastically increased photocatalytic activity of S, N-GQDs in solar light responsive integrating reactions of amines in aerobic conditions into the corresponding derivative of imines are also completely scrutinized. [ABSTRACT FROM AUTHOR]

Betulin is a naturally originating terpenoid, which attracted the attention of researchers due to its bioactive properties, including antitumor activity. This paper reports new betulin-imine derivatives, their synthesis, structural characterization and investigation of their antioxidant and anticancer activities. To this aim, a betulin aldehyde has been firstly prepared via an oxidation reaction using a Tempo reagent, which was further reacted with a series of aliphatic amines via an acid condensation reaction. The proposed chemical structures were confirmed using 1H-NMR and FTIR spectroscopy and single crystal X-ray diffraction, and characterized by solubility tests, ultraviolet-visible (UV-Vis) and photoluminescence spectroscopy, thermogravimetric analysis and polarized light microscopy. All the compounds were easily soluble in common organic solvents, and showed good thermal stability. They showed strong birefringence under polarized light indicating their crystalline nature, which was attributed to single crystal diffraction and they belong to the Sohnke P212121 space groups. The investigation of optical properties using photoluminescence spectroscopy revealed that all the imines emitted blue light in solution and in the solid state. The DPPH radical scavenging test showed that the antioxidant activity of betulin was significantly improved by imination with the increase of the aliphatic chain length. The antitumor activity investigated in vitro using the MTS assay on human breast cancer cell line MCF-7 (adenocarcinoma) and on non-tumorigenic epithelial cell line MCF-10A showed that the betulin-imine derivatives have improved antitumor activity and selectivity compared to neat betulin, suggesting that a medium length of the alkyl chain is favorable for the antiproliferative activity. [ABSTRACT FROM AUTHOR]

Imidazo[1,2-a]pyrimidine derivatives bearing imine groups (3a-e) were successfully synthesized in moderate to good yields using microwave-assisted heating. Corresponding amine derivatives (4a-e) were also obtained by the reduction reaction of the imine derivatives (3a-e). All synthesized products were characterized by FT-IR, ¹H NMR, 13C NMR, and LC-MS spectroscopic techniques. In silico ADMET, Lipinski, and drug-likeness studies of the compounds were conducted and all were found to be suitable drug candidates. The cytotoxicity of the potential drug molecules was screened against the breast cancer cell lines MCF-7 and MDA-MB-231 and the healthy model HUVEC by the sulforhodamine B method. According to the antiproliferative studies, compounds 3d and 4d showed remarkable inhibition of MCF-7 cells with IC50 values of 43.4 and 39.0 μM and of MDA-MB-231 cells with IC50 values of 35.9 and 35.1 μM, respectively. In particular, compound 3d selectively inhibited the proliferation of MCF-7 1.6-fold and MDA-MB-231 2.0-fold relative to healthy cells. Moreover, the apoptotic mechanism studies indicated that compound 4d induced apoptosis by moderately increasing the ratio of Bax/Bcl-2 genes. Imidazo[1,2-a]pyrimidine derivative 3d, a promising cytotoxic agent, may be helpful in the discovery of new and more efficient anticancer agents for breast cancer treatment. [ABSTRACT FROM AUTHOR]

The chemistry of fluorinated compounds has experienced extraordinary growth in recent decades due to the many and varied properties which many of the compounds that contain fluorinated groups possess. Among all of them, fluorinated chiral imines, in particular the Ellman's imines, are of great importance since they are some of the most interesting building blocks for the synthesis of a large number of enantioenriched carbocycles and heterocycles with extraordinary biological and synthetic properties. This personal account covers the most significant results obtained in our research group in the last two decades concerning asymmetric tandem reactions, paying special attention to the intramolecular aza‐Michael reaction (IMAMR), diversity oriented synthesis (DOS), asymmetric tandem reactions involving a p‐tolylsulfinyl group as chiral inducer and cycloaddition processes, in particular, the Pauson‐Khand reaction, [2+2+2]‐cycloadditions and metathesis reactions, starting mainly from enyne compounds and through the use of fluorinated chiral N‐sulfinyl imines and their derivatives as starting materials. [ABSTRACT FROM AUTHOR]

Currently, numerous ongoing studies are investigating the interaction of free radicals with biological systems, such as lipids, DNA and protein. In the present work, synthesis, characterization, antioxidant, DNA binding and molecular docking studies of Schiff base ligand and its Ni(II), Co(II), Cu(II) and Zn(II) were evaluated. The metal complexes have shown significant dose-dependent antioxidant activities higher than those of the free ligand but lesser than those of the standard antioxidant, ascorbic acid. The DNA binding constants (Kb) were found in the order Zn(pimp)2 {9.118 × 105 M−1} > H-pimp {3.487 × 105 M−1} > Co(pimp)2 {3.090 × 105 M−1} > Ni(pimp)2 {1.858 × 105 M−1} > Cu(pimp)2 {1.367 × 105 M−1}. Binding constants (Kb) values calculated from the molecular docking analysis were found to be in close agreement with the experimental results. The obtained results indicate the importance of synthesis complexes as a source of synthetic antioxidants and anticancer drugs. [ABSTRACT FROM AUTHOR]

Imine or Schiff base formation is considered as a key event in the catalytic mechanisms of many enzymes and in certain biological transformations, including glycation. In this process, less stable amino-acid-derived Schiff bases rearrange into more stable ketoamines or Amadori products. Schiff bases are also stipulated to be stabilized through complexation with metal ions, or through intramolecular cyclization to form more stable and reversible cyclic isomers, such as oxazolidin-5-ones. These intermediates can be easily detected relative to Schiff bases due to their higher stability. In this study, high-resolution mass spectrometry and isotope labeling techniques were used to identify labile imines as their oxazolidin-5-one derivatives in heated reaction systems of glucose/alanine/FeCl2, including their 13C-labeled counterparts. The reaction mixtures were heated for 2h at 110 °C and were analyzed by high resolution qTOF/MS for the presence of masses corresponding to Schiff bases of α-alanine with short chain aldehydes that can be generated from glucose degradation and also for the incorporation of 13C-labeled atoms from 13C-3 alanine and 13C-U glucose. Analysis of the data has indicated that Schiff bases can indeed be detected in the form of oxazolidin-3-ones, when methanol is used as the solvent. Furthermore, it was discovered that metal-ion-stabilized Schiff bases, in addition to forming oxazolidin-3-ones, can also undergo aldol addition with short chain sugars and initiate oligomerization reactions, leading to the formation of dimeric or trimeric oxazolidin-3-one oligomers, as demonstrated by their characteristic MS/MS fragmentations. [ABSTRACT FROM AUTHOR]

Background: Search for the better anti-cancer agents become central part for many research teams as the current drugs in use suffer lack of specificity to the cancer targets. Design and development of target specific anti-cancer agents increase the potency and safety of the drugs. Materials and Methods: Current research intends to develop a novel series of the pyrimidine derivatives owing to the anti-cancer potential of the pyrimidine scaffold. In a multicomponent reaction approach, 4,5-disubstituted pyrimidines (4) were synthesized from three component coupling reaction of substituted enamine (1), an orthoester (triethoxy methane) (2) and ammonium acetate (3). 4,5-disubstituted pyrimidines (4) were oxidized to corresponding aldehyde derivative (5) via Stephen aldehyde synthetic process. Then the pyrimidine aldehyde coupled with various aromatic amines to produce final pyrimidine imine derivatives (6a-6j). By using IR, 1 H-NMR, and mass spectral studies, all the prepared derivatives were characterized and subjected to anti-cancer activity evaluation by MTT Assay. Four cancer cells (A 549 (lung), B16F10 (mouse skin melanoma), SiHA (cervical), MCF-7 (breast), and one normal fibroblast (L929)] were employed to study the anti-cancer potential of the synthesized pyrimidine derivatives. Results: The synthesized compounds produced in moderate to good yields with proposed scheme of synthesis. All the synthesized derivatives displayed noticeable cytotoxicity against the tested cancer cell lines. Conclusion: All of the evaluated cell lines were susceptible to the potential cytotoxicity of the newly synthesized novel pyrimidine derivative. These brand-new pyrimidine compounds may be transformed into potent anti-cancer lead molecules. [ABSTRACT FROM AUTHOR]

Thiofentanyl is a potent analgesic and anesthetic drug that belongs to the microreceptor agonist group and is mainly used in animal's anesthesia. We present an optimized synthesis route for synthesis of thiofentanyl using nanocatalysts such as MCM‐41‐SO3H and SBA‐15‐Ph‐PrSO3H as green, heterogeneous and recyclable catalysts according to the strategy. The intermediate 2‐(thiophen‐2‐yl) ethyl methanesulfonate (1) easily obtained after conversion of the alcohol functional group into the mesylate leaving group using methanesulfonyl chloride (97% yield). The alkylation of commercially available 4‐piperidone monohydrate hydrochloride with 2‐(thiophen‐2‐yl) ethyl methanesulfonate in the presence of phase transfer catalyst was then carried out giving N‐[2‐(2‐thienyl) ethyl]‐4‐piperidone (2) with 90% yield. N‐[2‐(2‐thienyl)ethyl]‐4‐piperidone was then reacted with aniline in the presence of MCM‐41‐SO3H catalyst giving the imine derivative which reduced with sodium triacetoxyborohydride to N‐phenyl‐1‐(2‐(thiophen‐2‐yl)ethyl) piperidine‐4‐amine (ANTP) (4) with 80% yield. ANTP was finally acylated using propionyl chloride to achieve thiofentanyl (5) with 90% yield. High yields, mild reaction conditions, decreased reaction times, and convenient workup were the advantages of this method compared to the previous work. [ABSTRACT FROM AUTHOR]

1 H -Isochromenes and 1,2-dihydroisoquinolines are synthesized by regioselective indium(III)-catalyzed intramolecular hydrofunctionalization of o -(alkynyl)benzyl derivatives. The reaction with o -(alkynyl)benzyl alcohols and amines proceeds using indium triiodide (5–10 mol%) in toluene at 80–100 °C via regioselective 6- endo - dig intramolecular alkyne hydroalkoxylation or hydroamination in good yields. Alternatively, the cycloisomerization reaction of o -(alkynyl)benzaldehydes and imine derivatives using InI3 (5 mol%) and the Hantzsch ester (120 mol%) takes place, under milder reaction conditions, to give a variety of functionalized 1 H -isochromenes and 1,2-dihydroisoquinolines through a domino cycloisomerization/reduction approach. [ABSTRACT FROM AUTHOR]

A sustainable oxidation reaction of amines in water is established for the synthesis of imines and amides employing environmentally benign molecular iodine as the sole oxidant. The features of the present reaction also include no use of transition metals, operational simplicity and gram‐scale synthesis. It provides a facile access to imine and amide derivatives including bioactive molecules from readily accessible amine precursors. [ABSTRACT FROM AUTHOR]

Fifteen imine compounds were synthesized from the condensation of (Z)‐3‐(4‐bromophenyl)‐3‐(5‐methyl‐2‐thioxo‐1,3,4‐thiadiazol‐3(2H)‐yl) acrylaldehyde and various derivatives of primary amine, and their crystal structure was validated by single‐crystal XRD. Hirshfeld surface studies comprehensively explore intermolecular interactions in crystal packing. A state‐of‐the‐art dual computational strategy using quantum chemistry and molecular docking methodologies illuminates the molecular structure, electronic characteristics, and bioactivity of synthesized imines. Optimized and experimental molecule geometries were compared. By the agar well diffusion method, the synthesized imines were tested for antibacterial and antifungal activity against E. Coli, S. Aureus, A. Niger, and C. Albicans respectively. Based on their biofunctions synthesized imine derivatives were tested for their ability to inhibit E. Coli, C. Albicans, and ACE2. We observed that imine interaction energy values were excellent. We anticipate the current combination study using experiments and computational tools will attract the scientific community and inspire further in vitro and in vivo research. [ABSTRACT FROM AUTHOR]

The significance of chiral α-tertiary amines in medicinal chemistry and drug development has been unquestionably established in the last few decades. α-Tertiary amines are attractive structural motifs for natural products, bioactive molecules and pharmaceuticals and are preclinical candidates. Their syntheses have been the focus of intensive research, and the development of new methods has continued to attract more and more attention. In this review, we present the progress in the last decade in the development of synthetic methods for the assembly of chiral ATAs via transition-metal catalysis. To date, the effective approaches in this area could be categorized into three strategies: enantioselective direct and indirect Mannich addition to ketimines; umpolung asymmetric alkylation of imine derivatives; and asymmetric C–N cross-coupling of tertiary alkyl electrophiles. Several related developing strategies for the synthesis of ATAs, such as hydroamination of alkenes, HAT amination approaches and the C–C coupling of α-aminoalkyl fragments, are also described in this article. These strategies have emerged as attractive C–C and C–N bond-forming protocols for enantioselective construction of chiral α-tertiary amines, and to some extent are complementary to each other, showing the prospect of application in medicinal chemistry and chemical biology. [ABSTRACT FROM AUTHOR]

The deprotonative functionalization of α,α‐difluoromethyl ketones is described herein. Using a catalytic organosuperbase and a silane additive, the corresponding difluoroenolate could be generated and trapped with aldehydes to deliver various α,α‐difluoro‐β‐hydroxy ketones in high yields. This new strategy tolerates numerous functional groups and represents the access to the difluoroenolate by direct deprotonation of the difluoromethyl unit. The diastereoselective version of the reaction was also investigated with d.r. up to 93 : 7. Several transformations were performed to demonstrate the synthetic potential of these α,α‐difluoro‐β‐hydroxy ketones. In addition, this method has been extended to the use of other electrophiles such as imines and chalcogen derivatives, and a difluoromethyl sulfoxide as nucleophile, thus leading to a diversity of difluoromethylene compounds. [ABSTRACT FROM AUTHOR]

The current assignment depicts the structure of recent quinoline derivatives. This method begins with the structure of imine derivatives through the condensation reaction of ethyl 2-aminobenzoate with various substituted aliphatic aldehydes and ketones in the existence of sodium hydroxide as a catalyst. While the second step includes the intra-cyclization process of the imine compounds in presence of a base like tertiary butoxide that resolute installs the hydroxyl-group on the bicyclic skeleton and aromatic amines. The molecular docking program Flare V4.0 was applied to investigate the biological activities of divers produced compounds against E.coli bacteria. Spectral data support the compounds of each the recent outputs acquired during this assignment. [ABSTRACT FROM AUTHOR]

An imine derivative, N,N′‐bis‐(2‐hydroxo‐3‐ethoxy‐benzylidene)‐cyclohexane‐1,2‐diamine have been explored for the synthesis of a new Fe(III) complex (F3), the structure of which is confirmed by single crystal X‐Ray diffraction (SC‐XRD) analysis. The F3 is very sensitive for selective optical recognition of H2PO4−in DMSO/H2O (4/1, v/v) media. The interaction of F3 with H2PO4− allows nano‐molar (91.17 nM) level detection of H2PO4− having association constant, 6.92×104 M−1. In addition, F3 is found to have an efficient anti‐cancer activity against human breast cancer cell line MCF7 and MDA‐MB‐231. [ABSTRACT FROM AUTHOR]

The S(O,N)‐benzyl ethers of N‐arylquinone imines undergo cyclization under the action of bases to form products of the benzothiazol, benzoxazole, and benzimidazole series, while under thermal conditions they undergo a non‐catalyzed rearrangement to form spiro‐cyclohexadiene derivatives of benzazines. The benzimidazole, spirobenzothiazine, and spirobenzoxazine structures were supported by the x‐ray diffraction method. The possibility of intramolecular photochemical cyclization was investigated; ortho‐S(O,N)‐benzyl‐substituted N‐arylquinone imines show high photostability under UV irradiation. The features of the cyclization processes of quinone imine derivatives were revealed by DFT calculations using the wB97XD/6‐311++G** method. [ABSTRACT FROM AUTHOR]

[Display omitted] Aminoglycosides are well known, cationic antimicrobial drugs. However, biofilm-based antibiotic resistance significantly limits their efficacy. Masking the polycationic character of these drugs, followed by incorporation into self-emulsifying drug delivery systems (SEDDS) can improve biofilm eradication. Imine derivatives were synthesized via coupling with trans -cinnamaldehyde and characterized regarding degree of substitution, logP, cytotoxicity and antimicrobial efficacy on the opportunistic human pathogens Escherichia coli , Staphylococcus aureus and Candida albicans. Imines were loaded into newly developed SEDDS formulations and the antimicrobial efficacy was assessed on these pathogens in planktonic state and after biofilm formation. Successful synthesis of imine derivatives with almost entirely masked amine groups was confirmed by NMR, FT-IR, TLC and MS. Imines exhibited a marked elevation in logP value of 8 units for kanamycin and 7.7 units for tobramycin. They showed low toxicity profiles while fully preserving antimicrobial efficacy on all tested pathogens. Incorporation into SEDDS resulted in nanoemulsions, which exhibited equal antimicrobial efficacy on the model germs compared to the corresponding aminoglycosides. Moreover, the biofilm eradication assay revealed superior anti-biofilm properties of the nanoemulsions. Native aminoglycosides were largely prone to reduced microbial susceptibility due to biofilm formation, while the combination of SEDDS with iminated aminoglycosides provided overall enhanced biofilm eradication. [ABSTRACT FROM AUTHOR]

In the present communication, we conceived a new synthetic approach for the preparation of novel thiazolyl-lactam/thiazole analogs. The reaction was started through cyclization of ketone with thiourea along with substituted aryl aldehydes to culminate imine derivatives which subsequently cyclized with thioglycolic acid/chloroacetyl chloride to produce final compounds. The structural elucidation of newly synthesized compounds was performed through elemental detections, FT-IR, 1HNMR, and Mass spectrometric techniques. Antimicrobial studies were performed for all synthesized molecules by serial dilution method by tacking the positive (K. pneumonia, S. aureus, B. subtills) and negative (P. aeruginosa and E. coli.) bacterial strains. The in vitro antimicrobial screening results show that the compounds 2e, 3c, and 3d containing o-hydroxy, p-chloro, and p-nitro substituent respectively exhibit exceptional activity against S. aureus while compounds 2d and 3f bearing p-nitro and o-chloro substituent respectively were deemed to be the most competent against B. subtilis. Compounds 2d (p-nitro) and 2f (o-chloro) were found to be most potent against E. coli. In gram-negative bacterial strains, compounds 2c (p-chloro), 2g (4-OH,-OCH3), 3b (phydroxy), and 3e (o-hydroxy) were extremely potent against P. aeruginosa while compound 2e containing o-hydroxy group shows excellent activity against E.coli. [ABSTRACT FROM AUTHOR]

[Display omitted] • New linear and cyclic arylsulfonamides were synthesized and characterized. • Significant inhibition against tumor expressed hCA IX/XII isoforms was detected. • Docking simulations suggested the poses into hCA IX and hCA XII cavities. A small series of arylsulfonamide derivatives was designed and synthesized to study linear and cyclic inhibitors targeting human Carbonic Anhydrases (hCAs EC 4.2.1.1) as essential enzymes regulating (patho)-physiological processes. Particularly, the synthesis of these ten compounds was inspired to the well-known arylsulfonamides having flexible or constrained linkers able to maintain the two crucial moieties, anchoring zinc group and hydrophobic tail, in the optimized orientation within CA cavities of tumor-expressed isoforms hCA IX and hCA XII. The synthesized imine derivatives and related cyclic 1,3-thiazin-4-ones were screened in a stopped-flow carbon dioxide hydrase assay and proved to be effective inhibitors against hCA IX and hCA XII isoforms with K i values ranging of 3.7–215.7 nM and 5.7–415.0 nM, respectively. Molecular docking studies of both series of arylsulfonamides were conducted to propose their binding mode within hCA IX and hCA XII active sites thus highlighting their distinct ability to occupy the two catalytic cavities. Moreover, the 4-[(3-cyanophenyl)methylidene]aminobenzene-1-sulfonamide 7 proved to reduce the cell viability of breast carcinoma (MCF-7) and colon rectal carcinoma (HCT-116) human cell lines under the fixed doses of 10 μM. These results encouraged us to continue our efforts in developing potent and efficient arylsulfonamides targeting hCA IX and hCA XII isoforms. [ABSTRACT FROM AUTHOR]

• A number of novel π-extended fluorescent 2,5-substituted indolizines prepared. • Promising " OFF-ON " type fluorescence sensors to monitor oxidative processes in biological systems. • Large stokes shifts observed for the novel indolizines (71-171 nm/2955-6761 cm-1). • Imine and olefin derivatives exhibited fluorescence both in solution and the solid state. We report herein the synthesis of novel π-extended fluorescent 2-aryl-indolizines bearing substituents such as chalcone, styrene and imine groups at the C-5 position of the indolizine. Absorption and fluorescence properties of these 2,5-substituted indolizines were significantly affected by the substitution pattern at the C-5 position, as evidenced by absorption spectra, Stokes shifts and fluorescence measurements. Among the indolizine derivatives, those containing chalcone exhibited a highly notable red shift in their maximum wavelength of fluorescence (λ em = 650 nm) compared to those containing imine (λ em = 487 nm) or olefin (λ em = 543 nm), accompanied by relatively large Stokes shifts (71-171 nm / 2955–6761 cm−1) and fluorescence quantum-yield values from 0.002 to 0.296. All synthesized indolizines demonstrated colorful in solution, while the imine- and olefin-substituted indolizines exhibited fluorescence both in solution and the solid state. The chalcone derivatives showcased the capability to regulate its fluorescence modulation. Although the presence of the carbonyl group extensively suppressed this effect, it was significantly restored upon reduction to the hydroxyl group, demonstrating a promisor " off-on " fluorescent sensors for monitoring oxidative processes within biological systems. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • Tuning the structures of three antipyrene based imine derivatives allows optical recognition of Al3+ and/ Zn2+ ions. • The structures of the probes have been confirmed by X-ray diffraction analysis while the interaction of the probes with the analyte has been established by various spectroscopic studies. • The A3 can simultaneously recognize Al3+ and Zn2+ at two different wavelengths (λ em = 505 nm and 539 nm respectively) at nano-molar level. • Theoretical DFT studies firmly support the experimental findings. Three imine derivatives containing antipyrine moiety viz. A1, A2 and A3 have been synthesized and characterized by SC-XRD analysis. The molecules are weakly fluorescent due to ESIPT process. The A1 and A2 have high affinity as well as selectivity for Al3+ that allow its nano-molar level detection. On the other hand, A3 interacts with both Al3+ and Zn2+ as reflected from the change of emission profiles at two different wavelengths. Such distinctive photo-physical interaction of A3 over A1 and A2 may be elucidated through hard-soft interaction concept. Various spectroscopic techniques have been used to explain the sensing mechanism. DFT studies have been performed to explain and justify experimental findings. The interaction of A3 towards Al3+ and Zn2+ has been utilized to construct a logic gate. Moreover, real water analysis has also been performed. [ABSTRACT FROM AUTHOR]

[Display omitted] • A novel C1 symmetric Binol imine Schiff base fluorescence sensor named (Sa , R)-6 was synthesized and structurally characterized. • (Sa , R)-6 showed both significant visual and fluorescence response with the presence of Al3+. • As an Al3+ probe, (Sa , R)-6 demonstrated a nanomolar LOD and good interference immunity. • (Sa , R)-6 can be utilized for monitoring Al3+ concentration in a human normal astrocyte cell line HA-1800 via confocal fluorescence imaging. A novel C1 symmetric Binol imine Schiff base fluorescence sensor (Sa , R)- 6 was designed and synthesized by using (S)-Binol-3-aldehyde as initial material. The probe showed great fluorescence enhancement at λ = 552 nm and visual light yellow fluorescence under 365 nm UV lamp irradiation with presence of Al3+. Quantitative test was feasible from 10 μM to the detection limit which reaches nanomole level. Job's plot, HRMS spectroscopic and NMR titration indicated the formation of Al[(Sa , R)- 6 ]2+. DFT calculations suggested the coordination reaction lead to a CHEF effect and the "turn-on" fluorescence response. Moreover, (Sa , R)- 6 was well tolerable to human normal astrocyte cell line HA-1800 in cell viability test so that it could be utilized for detecting trace Al3+ in vitro in a concentration-dependent manner via confocal imaging which proved its potential of diagnosis and treatment of Aluminum related diseases. [ABSTRACT FROM AUTHOR]

Two ferrocenyl imine derivatives (3 and 4) were prepared from 5-(2-nitrophenyl)-2-furancarboxaldehyde and 5-(4-nitrophenyl)-2-furancarboxaldehyde. Both complexes (3 and 4) have been characterized using HRMS, FT-IR, NMR, X-ray diffraction, and cyclic voltammetry. In the in vitro biological tests, complex 3 showed the most promising antiparasitic activity against T. brucei parasite. [Display omitted] • New ferrocenyl-based imines (3 and 4) were synthesized from nitrophenyl-2-furan with antitrypanosomal properties. • The crystal structures of these ferrocenyl imine complexes have been determined by single-crystal X-ray diffraction. • Both complexes exhibited suitable stability in mixtures DMSO:Buffer (20:80). • The results demonstrate a significant antiparasitic effect of the ferrocene derivative (3) against T. brucei. • The Selectivity Index values of Schiff bases compounds against T. brucei was 3 > Nfx > 4. Two new metallocene complexes with formulation [Fe(η5-C 5 H 5){(η5-C 5 H 4)-N CH-2-C 4 H 2 O-(5-C 6 H 4 -2-NO 2)}] (3) and [Fe(η5-C 5 H 5){(η5-C 5 H 4)-N CH-2-C 4 H 2 O-(5-C 6 H 4 -4-NO 2)}] (4) have been synthesized and their antitrypanosomal activity has been evaluated. Complexes 3 and 4 were obtained by condensation reaction of ferrocenylamine (1) with respective 5-(2-nitrophenyl)-2-furancarboxaldehyde (2a) or 5-(4-nitrophenyl)-2-furancarboxaldehyde (2b). The complexes were fully characterized by spectroscopic techniques (FT-IR, 1H and 13C{1H} NMR, and HRMS), which confirm their correct obtainment. The crystal structures of 3 and 4 were also determined by single crystal X-ray diffraction. Furthermore, UV–visible studies revealed that compounds 3 and 4 exhibited suitable stability in DMSO:HEPES buffer solution (80:20) throughout 24 h. The in vitro antiparasitic activities of ferrocenyl imine derivatives 3 and 4 were assessed against two species of parasites, Trypanosoma cruzi (T. cruzi) and Trypanosoma brucei (T. brucei). The obtained results revealed that compound 3 (EC 50 = 0.44 μM) exhibited nearly a 40-fold greater efficacy as an anti- T. brucei agent compared to derivative 4 (EC 50 = 16.0 μM). Moreover, compound 3 demonstrated superior potency when compared with its organometallic analogs (EC 50 = 2.42–13.3 μM), which were previously reported by our research group. Interestingly, the EC 50 value of 3 was found to be 8 times greater than that of nifurtimox (EC 50 = 3.56 μM). The cytotoxicity of the ferrocenyl imines was also evaluated on the L 6 rat skeletal myoblast cell line. [ABSTRACT FROM AUTHOR]

Herein, we present a novel method to synthesize imine and its derivatives using aromatic aldehydes and HCOONH4 in DMSO. HCOONH4 functions as both the nitrogen source and hydrogen source. And a continuous condensation‐reduction (CCCR) mechanism was proposed. Moreover, the HMQC spectrum indicated the generation of (PhCH=N)2CHPh, which was the key intermediate of the CCCR route. [ABSTRACT FROM AUTHOR]

Objective: Glutathione (GSH) is a tripeptide consisting of glycine, glutamic acid and cysteine. If the sulfur containing amino acids like methionine and cysteine increase in the cells, the level of GSH increases. GSH is one of the most important and powerful antioxidants in the body and it reduces oxidative stress. Reduction of GSH affects apoptosis activity and multidrug resistance proteins (MRPs). In the present study, we investigated the effects of sulfur-containing glycine imine derivatives on MRPs and apoptosis mechanism in the MCF-7 (breast cancer) and DLD-1 (colon cancer) cell lines. Methods: In MCF-7 and DLD-1 cell lines; mRNA levels of MRPs (ABCB1, ABCC3, ABCC10, ABCC11 and ABCG2), apoptosis mechanism proteins (BAX, BACL-2, P53, PARP, CASP3), heat shock proteins (HSPs) and endoplasmic reticulum chaperone proteins (GRPs) were determined by qRT-PCR method. Results: Compounds decreased gene expression of multiple drug resistance (MDR) genes and increased gene expression of pro- apoptosis mechanism genes (BAX, P53, CASP3). HSPs and BCL- 2 and PARP gene expressions decreased. There was no significant decrease in gene expression of GRPs. The compounds were shown to have remarkable effects on MDR genes (ABCB1, ABCC10, ABCC11 and ABCG2) other than ABCC3. Compounds were found to have significant effects on apoptosis mechanism genes and HSPs. Conclusion: Our results indicate that the sulfur-containing glycine imine derivatives can be a potent option as a cancer drug, especially in breast and colon cancers. [ABSTRACT FROM AUTHOR]

The imination of a cage‐opened fullerene C60 derivative was examined using N,N‐dimethyl‐1,4‐phenylenediamine. The desired imine derivative showed a remarkably intense near‐infrared (NIR) absorption band (λedge=1050 nm). According to theoretical calculations, the longest wavelength absorption is assignable to the HOMO→LUMO transition with a strong charge‐transfer character, in which the HOMO localizes on the introduced imine moiety while the high LUMO coefficients can be seen over the entire C60 skeleton. It should be noted that the two reduced compounds bearing an amine or methylene group were also formed in the reaction producing the imine derivative, the former of which again showed NIR absorption tailing to 1200 nm. In this reduction, the hydride source is considered to be α‐hydrogen of the diamine so that the use of N,N,N',N'‐tetramethyl‐1,4‐phenylenediamine increased the yield of the methylene derivative up to 20%. [ABSTRACT FROM AUTHOR]

Three new 4-phenylpicolin derivatives with a thiosemicarbazone structure were synthesized and evaluated for tuberculostatic activity. The compounds were obtained by the condensation of methyl 4-phenylpicolonimidate with the corresponding cycloalkylamino-1-carbothiohydrazides. The 1H NMR temperature spectra obtained showed proton lability at the nitrogen atom N2, and X-ray crystallography confirmed the zwitterionic structure of all products. ADME calculations indicate that the compounds can be tested as future drugs. All compounds were absorbed in the gastrointestinal tract. All compounds also showed very good tuberculostatic activity (MIC 3.1–12.5 µg/mL). Derivative 1b showed the best selectivity for M. tuberculosis compared to the other pathogenic species tested. The study has allowed the emergence of imine derivative 1b as a good structure for further optimization in the search for antitubercular drugs. [ABSTRACT FROM AUTHOR]

Series of new derivatives of ninhydrin, isatin, and 4-hydroxy-1,3-thiazine-2,6-dione were synthesized. Their antimicrobial activity against opportunistic microflora of Staphylococcus aureus and Pseudomonas aeruginosa isolated from neurotrophic ulcers of leprosy patients was studied. Antibacterial activity against S. aureus was observed for derivatives of chalcone (MIC 2.31 ± 0.99 and 8.0 ± 2.83 μg/mL), benzofuran (MIC 3.5 ± 1.66 μg/mL), imines (MIC 0.56 ± 0.16 and 3.01 ± 1.68 μg/mL), and indene (MIC 1.38 ± 0.38 μg/mL). Derivatives of imine (MIC 0.25 ± 0.05 and 0.63 ± 0.26 μg/mL) and indene also exhibited pronounced inhibitory effects against P. aeruginosa. Bactericidal effects on both cultures were observed for 5-{(1E)-1-[2-(1-benzothiophen-2-yl)hydrazinylidene]-ethyl}-4-hydroxy-2H-1,3-thiazine-2,6(3H)-dione. An indene derivative with a morpholine fragment showed a pronounced bactericidal effect (MBC 2.3 ± 0.58 μg/mL) on the growth of P. aeruginosa culture. [ABSTRACT FROM AUTHOR]

Urease inhibition is therapeutically important for the treatment of diseases such as peptic and duodenal ulcers, and urolithiasis (kidney stone disease) caused by the ureolytic bacteria. Functionalization of 2‐amino‐4‐chloropyridine scaffold was conducted by using single step chemical transformation to yield thiourea, and imine derivatives (1–35). Among these, compounds 3, and 16–35 were identified as new compounds. All analogous exhibited significant urease inhibition activity with IC50 in the range of 8.36–55.8 μM. Acetohydroxamic acid (IC50=20.4±0.23 μM) was used as standard. All synthesized compounds were characterized by using spectroscopic techniques such as 1H‐NMR, 13C‐NMR, NOESY, COSY, HMBC, HSQC, IR, UV, and mass spectrometry. Furthermore, kinetic studies were performed in order to determine the mode of interaction of these compounds with urease enzyme. Molecular docking and kinetic studies revealed that the compounds 25, and 26 are competitive inhibitors of urease enzyme. All the compounds were tested for their cytotoxicity against normal cell line and were found to be non‐cytotoxic. [ABSTRACT FROM AUTHOR]

The higher–order cycloaddition reactions of four cycloheptatriene (CHT) derivatives, heptafulvene, tropone, and the imine and ylidenehydrazine derivatives with ethylene, electrophilic dicyanoethylene (DCE), and nucleophilic cyclic ketene acetal (CKA) have been studied within the molecular electron density theory (MEDT) at the ωB97X-D/6-311G(d,p) level. The electron localization function (ELF) indicates that the substitution at the X8 position of these CHTs only affects the electron density of the C1–X8 bonding region, and the CHT core being only slightly polarized. The reactivity indices classify heptafulvene and the two nitrogen derivatives as strong nucleophiles and tropone and the ylidenehydrazine as strong electrophiles participating in polar reactions. Parr functions show that the C2 and C4 positions are the more electrophilic, while the X8, C2, and C4 positions are the more nucleophilic of these CHTs. The activation energies of these CHTs decrease in the order: ethylene > CKA > DCE in agreement with the reactivity indices. The polar cycloaddition reactions with DCE are completely regioselective, while the reactions of heptafulvene and the imine with CKA are highly regio- and pseudocyclic selective, yielding the [4+2] cycloadducts, and those of tropone and ylidenehydrazine are highly regio- and pseudocyclic selective yielding the [8+2] cycloadducts. This MEDT study makes it possible to explain how the substitution at the X8 center of these CHTs changes the reactivity and selectivity of these higher-order cycloaddition reactions. [ABSTRACT FROM AUTHOR]

The isothiourea-catalyzed formal enantioselective conjugate addition of 2-hydroxybenzophenone imine derivatives to α,β-unsaturated para-nitrophenyl esters has been developed. Investigations of the scope and limitations of this procedure showed that β-electron withdrawing substituents within the α,β-unsaturated ester component are required for good product yield, giving rise to a range of β-imino ester and amide derivatives in moderate to good isolated yields with excellent enantioselectivity (20 examples, up to 81% yield and 97 : 3 er). [ABSTRACT FROM AUTHOR]

• Synthesis of a new range of a range of novel indolyl imines derivatives are presented. • The antioxidant potentials of the targeted compounds are examined. • The compounds 3e provided better α-glucosidase enzyme inhibition value than the standard acarbose. • Molecular docking studies reveal the structural insights of indolyl imine compounds by the interactions on the selected enzymes. A new range of indolyl imine system 3d-l has been successfully prepared from 4,6-dimethoxy-2,3-diphenyl-indole-7-carbaldehyde 2a and 4,6-dimethoxy-3-aryl-indole-7-carbaldehyde 2b-c via Schiff base reaction. The structure of targeted compounds was confirmed by 1H and 13C NMR, FT-IR, mass spectrometry and single crystal X-ray diffraction techniques. The indolyl imine derivatives were also subjected to in vitro antidiabetic activities employing α-glucosidase and α-amylase enzymes. In terms of antidiabetic investigation, the α-glucosidase enzyme was found to be potential target due to the comparable inhibition concentrations with the standard acarbose and the compound 3e exhibited better potency than the standard. The anticholinesterase potency of the compounds was investigated towards the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. The compounds displayed moderate efficiency against the BChE enzyme with the best inhibition concentration of 30.48 μM by the compound 3h. The antioxidant properties of final compounds were determined by DPPH radical scavenging, ABTS Cation Radical Decolarization and CUPRAC Cupric Reducing Antioxidant Capacity assay methods. The ABTS cation scavenging assay provided the best responses for the compounds and the candidates 3k and 3l were determined as promising targets for the antioxidant activity. Plausible binding mode and interaction of ligands with the selected enzyme have been studied by molecular docking, supporting the experimental results. In silico ADME showed high drug likeness of the synthesized compounds. [Display omitted] [ABSTRACT FROM AUTHOR]