Imine Derivatives Research Articles

Indolyl imine compounds as multi-target agents; synthesis, antidiabetic, anticholinesterase, antioxidant activities and molecular modeling

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-cvia 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.

4-Fluoro-benzyl (Z)-2-(2-oxoindolin-3-yl-idene)hydrazine-1-carbodi-thio-ate.

The title compound, C16H12FN3OS, a fluorinated di-thio-carbazate imine derivative, was synthesized by the one-pot, multi-component condensation reaction of hydrazine hydrate, carbon di-sulfide, 4-fluoro-benzyl chloride and isatin. The compound demonstrates near-planarity across much of the mol-ecule in the solid state and a Z configuration for the azomethine C=N bond. The Z form is further stabilized by the presence of an intra-molecular N-H⋯O hydrogen bond. In the extended structure, mol-ecules are linked into dimers by N-H⋯O hydrogen bonds and further connected into chains along either [20] or [100] by weak C-H⋯S and C-H⋯F hydrogen bonds, which further link into corrugated sheets and in combination form the overall three-dimensional network.

Thymol-based Dual Chemosensor for Optical Detection of Cu2+ and Pb2+ ions and Evaluation of its Toxicity Against Plant Growth Promoting Rhizobacteria

Abstract: Thymol is a naturally occurring monoterpenoid phenol, and its derivatives may emerge as eco-friendly materials for the development of chemosensing probes. To prepare a non-toxic chemosensing probe based on thymol moiety for the detection of metal ions. : A chemosensor (TPC) based on thymol was afforded by the reaction of thymol and piperidine in methanol. The structure elucidation of TPC was carried out with UV-Vis, 1H-NMR, 13C-NMR, and FT-IR analysis. The chemosensing properties of the synthesized probe were determined with UVvisible spectroscopy, and further, it was exploited for the determination of the concentration of Cu2+ and Pb2+ ions in spiked tap water samples. The toxicity studies of the chemosensing probe were conducted against the plant growth-promoting rhizobacteria (PGPR), i.e., Rhizobium sp., Pseudomonas sp., and Azospirillum sp. The absorption spectrum of TPC showed a band at 277 nm. The presence of Cu2+ and Pb2+ ions induced an increase in the absorption intensity at 277 nm by 2-fold and 1.5-fold, respectively. The binding constant for both TPC-Cu2+ and TPC-Pb2+ was calculated as 1.55 × 105 M-1 and 1.47 × 105 M-1, respectively. The respective limit of detection (LOD) and limit of quantification (LOQ) for Cu2+ were 623.64 × 10-6 mol L-1 and 1889.85 × 10-6 mol L-1. For Pb2+ ions, LOD and LOQ were calculated as 676.70 × 10-6 mol L-1 and 2050.60 × 10-6 mol L-1, respectively. In spiked tap water samples, percent recovery was observed in the range of 80.1 to 81.0 % and 80.1 to 81.9 % for Cu2+ and Pb2+ ions, respectively. Toxicity studies of the synthesized probe inferred that TPC was non-toxic against the tested PGPR at all the tested concentrations. In this work, we have synthesized a thymolbased chemosensor, which has been evaluated as a non-toxic sensor for Pb2+ and Cu2+ ions.

New sterically hindered disubstituted imine derivatives of (thia)calix[4]arenes bearing bulky tert-butyl groups at the lower rim: synthesis, structures, and complexation ability toward CoII and NiII cations in solution

New sterically hindered disubstituted imine derivatives of (thia)calix[4]arenes bearing bulky tert-butyl groups at the lower rim: synthesis, structures, and complexation ability toward CoII and NiII cations in solution

The Synthesis of Some Imine Derivatives via Condensation Reactions between Some Aromatic Phenylhydroxylamine Derivatives with Glyoxylic Acid and the Study of their biological activity

This study investigated the condensation reactions between N-(3,4-dimethoxybenzyl)hydroxylamine and N-(4-methylbenzyl)hydroxylamine with glyoxalic acid. The objective was to obtain imine derivatives as the desired target products. FT-IR, 1H-NMR, and 13C-NMR spectroscopic techniques were used to identify the structures of the produced compounds. Different conditions were considered for these reactions and only N-(3,4-dimethoxybenzyl)hydroxylamine could be converted to the desired nitrone. Finally, the antimicrobial efficacy was assessed in terms of its action against the bacteria Escherichia coli (E.coli) as Gram-negative bacteria, Staphylococcus aureus (S.aureus) as Gram-positive bacteria and fungus (Candida albicans). The activity data proved that this nitrone showed significant antimicrobial activity compared to standard drugs.

New homoleptic imine derivative of lawsone and its metal complexes: Preparation, characterization, in vitro and in silico biological investigation

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.

Asymmetric transfer hydrogenation of fluorinated ketone and imine derivatives: An efficient access to valuable building blocks

The introduction of fluorine substituents in a molecule is highly regarded in the pharmaceutical industry as attested by the growing number of fluorinated bioactive molecules approved by the Food and Drug Administration in recent years. In this context, enantiopure fluorinated alcohols and amines are particularly interesting building blocks for medicinal chemists. A particularly straightforward and efficient access to these structures relies on the asymmetric transfer hydrogenation of the corresponding fluorinated ketones and imines. This review aims at providing the developments carried out in this area, detailing transition metal-catalyzed as well as organocatalyzed reductions of these classes of compounds.

N6-ferrocenylcarbonyl derivatives of sydnone imines: synthesis, modification, growth-regulating and antidote against herbicide “Zinger” activities

The first N6-ferrocenylcarbonyl derivatives of sydnone imines were synthesized by the reaction of sydnone imine hydrochlorides with ferrocenoyl chloride. The possibility of deprotonation of C(4)-H of the oxadiazole ring in N6-ferrocenylcarbonyl derivatives of sydnone imines under the action of n-butyllithium was demonstrated. The reactivity of 4-lithio derivatives was studied and methods of their functionalization were developed. In vegetation experiments on corn seedlings, the growth-regulating properties and antidote activity against Metsulfuron-Methyl (Zinger WP) herbicide of the synthesized ferrocenyl containing sydnone imine derivatives were studied.

An Explicative Review on the Current Advancement in Schiff Base-Metal Complexes as Anticancer Agents Evolved in the Past Decade: Medicinal Chemistry Aspects.

In the recent era, developments in the field of bio-inorganic chemistry have improved interest in Schiff base complexes (imine scaffolds) for their pharmacological excellence in different areas. Schiff bases are a kind of synthetic molecule that is synthesized by the condensation reaction between a 1o amine and a carbonyl compound. Imine derivatives are also acknowledged for their ability to form complexes with several metals. Due to their wide range of biological activities, they have acquired prominence in the therapeutic and pharmaceutical industries. Inorganic chemists have continued to be intrigued by the vast range of uses of these molecules. Many of them are also thermally stable and have structural flexibility. Some of these chemicals have been discovered to be beneficial as clinical diagnostic agents as well as chemotherapeutic agents. Because of the flexibility of the reactions, these complexes have a wide range of characteristics and applications in biological systems. Anti-neoplastic activity is one of them. This review attempts to draw attention to the most notable examples of these novel compounds, which have excellent anticancer activity against different cancers. The synthetic scheme of these scaffolds, their metal complexes, and the explanation of their anticancer mechanism reported in this paper lead the researchers to design and synthesize more target-specific Schiff base congeners with little or no side effects in the future.

Synthesis of New Iminium Derivatives of Sulphonio-сloso-Decaborate Anion (Bu4N)[2-B10H9SC(NH2)R] (R = –CH3, –CH2CH3, –CH(CH3)2, –Ph, –PhCH3)

New iminium derivatives of the sulfonio-closo-decaborate anion have been obtained in the form of tetrabutylammonium salts (Bu4N)[2-B10H9SC(NH2)R] (R = –CH3, –CH2CH3, –CH(CH3)2, –Ph, –PhCH3), in which the iminium group acts as a protective group and allows further modification of the boron cluster anion without acting the sulfonium group. The compounds have been studied by elemental analysis, IR and 11B, 1H, 13C NMR spectroscopies. The structure of compounds (Bu4N)[2-B10H9SC(NH2)CH3] and (Bu4N)[2-B10H9SC(NH2)Ph] has been confirmed by X-ray diffraction analysis. The yield of final compounds is 80%.

Synthesis, Characterization, and Preliminary Evaluation of Antimicrobial activity of Imines derived from Vanillic Acid Conjugated to Heterocyclic

The purpose of this research is to prepare new vanillic acid derivatives with 1,2,4-triazole-3-thiol heterocyclic ring and evaluate their antimicrobial activity in a preliminary assessment. A multistep synthesis was established for the preparation of new vanillic acid-triazole conjugates. The intermediate of 4-(4-amino-5-mercapto-4H-1,2,4-triazol-3-yl)-2-methoxyphenol (4) reacts with different heterocyclic aldehydes (thiophene-2-carboxaldehyde, pyrrole-2-carboxaldehyde, thiophene-3-carboxaldehyde, and furfural ) in ethanol containing few drops of acetic acid yielded the corresponding 4-(4-(substituted amino)-5-mercapto-4H-1,2,4-1triazol-3-yl)-2-methoxy phenol derivatives (5-8). These compounds were characterized spectroscopically by FT-1IR and 1H-1NMR. These imine derivatives (5-8) were tested for their antimicrobial activity and compared with three different standard references (amoxicillin, ciprofloxacin, and fluconazole). Overall, compounds 6 and 8 exhibited varying degrees of inhibitory effects on the growth of the examined bacterial species and fungus. The most active one is compound 6 having pyrrole ring imine derivative showed potent activity against C. 1albicans and moderate activity against all tested bacteria compared to other derivatives but no activity toward P. 1aeruginosa and P. 1mirabilis.

Synthesis of new imine-/amine-bearing imidazo[1,2-a]pyrimidine derivatives and screening of their cytotoxic activity.

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.

Microwave-Assisted Semisynthesis and Leishmanicidal Activity of Some Phenolic Constituents from Lichens

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.

Synthesis of α-Hydroxyl and α-Amino Pyridinyl Esters via Photoreductive Dual Radical Cross-Coupling.

A method for the synthesis of α-hydroxyl and α-amino pyridinyl esters via photoreductive dual radical cross-coupling catalyzed by the super-organoreductant CBZ6 has been developed. A wide range of 2-pyridinylation and 4-pyridinylation of either α-ketoesters or imine derivatives has been achieved. The applications in the synthesis of pyridinyl amino-hydroxyl acids as well as a new chiral oxazoline ligand have also been accomplished.

N-unsubstituted Imidazoles: Design, Synthesis, and Antimicrobial Evaluation.

All the current antifungal azoles have one substituted nitrogen atom in their imidazole or triazole rings. In this study, eleven imine and amine derivatives of imidazole, in which both nitrogen atoms of the imidazole ring are unsubstituted, were designed and synthesized. Imine derivatives were prepared by condensation of imidazole-4-carboxaldehyde with appropriate amines, and then in the next step, using sodium borohydride, the imines were reduced to amine derivatives. Docking studies reveal unsubstituted nitrogen atom of the imidazole ring coordinated well with the heme molecule of the receptor. In vitro, antimicrobial evaluation was tested on Candida albicans, E. coli, and Staphylococcus aureus. Based on the results of the antimicrobial study, compound 10, which contains 4-chlorobenzyl moiety, proved to be the most potent compound against Candida albicans, and it was more active than the reference drug fluconazole and showed comparable activity to amphotericin B. Compounds 10 and 11 and compounds 8, 10 and 11 showed significant responses against E. coli and Staphylococcus aureus respectively. It is concluded that compound 10 can be acted as a new lead compound to find new azoles antifungal.

Photoinduced Nitroarenes as Versatile Anaerobic Oxidants for Accessing Carbonyl and Imine Derivatives.

Herein, we report a protocol for the anaerobic oxidation of alcohols, amines, aldehydes, and imines promoted by photoexcited nitroarenes. Mechanistic studies support the idea that photoexcited nitroarenes undergo double hydrogen atom transfer (HAT) steps with alcohols and amines to provide the respective ketone and imine products. In the presence of aldehydes and imines, successive HAT and oxygen atom transfer (OAT) events occur to yield carboxylic acids and amides, respectively. This transformation is amenable to a continuous-photoflow setup, which led to reduced reaction times.

Regioselective synthesis of some new pyrazole and isoxazole derivatives incorporating benzothiazole moiety: Experimental and theoretical studies

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.

Highly active primary amine ligated Ru(II)-arene complexes as selective catalysts for solvent-free N-alkylation of Anilines

Efficient Ru(II) catalysts with substituted aniline based ligands were synthesized having chemical formula [Ru(η6-p-cymene)Cl2(L1)] [Ru-1] and [Ru(η6-p-cymene)Cl2(L2)] [Ru-2] (where, L1 = 3,5-bis(trifluoromethyl)aniline and L2 = 3,4,5- trimethoxy aniline). The structural features of both the complexes were authenticated by ESI-MS, 1H and 13C NMR, FT-IR, elemental analyses, and single-crystal X-ray diffraction studies. Catalytic performance of both [Ru-1] and [Ru-2] was investigated for conversion of primary amine to secondary amine using alcohols under milder and solvent-free conditions and compared with the reported aniline-based Ru(II)-arene complex [Ru-3]. Among them, [Ru-1] could achieve 100% selectivity towards mono N-alkylated amines with > 99% conversion without formation of any imine derivatives. The results suggested that the lone pair of electrons of benzyl alcohol binds easily to the electron-deficient Ru(II) center of [Ru-1] catalyst making it more effective compared to electron-rich [Ru-2] and [Ru-3] catalysts. The catalytic performance of [Ru-1] demonstrates that it is one of the most active primary amine ligated Ru(II) based catalytic systems for N-alkylation of anilines under milder and solvent-free conditions.

Synthesis, Antioxidant, Molecular Docking and DNA Interaction Studies of Metal-Based Imine Derivatives.

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.

Dicyanovinyl-capped thiazologermoles with moderate donor-acceptor interaction as visible photoluminescence turn-on sensors for primary amines

Dicyanovinyl-capped thiazologermoles (DTzG-DCV and GIDTz-DCV) were synthesized, and their optical and electrochemical properties were investigated. Both DTzG-DCV and GIDTz-DCV showed solvatochromism, exhibiting red shifts of the photoluminescence (PL) bands with increasing solvent polarity from toluene to DMF, likely due to intramolecular donor–acceptor interaction. Moreover, they served as selective PL sensors, with spectral changes in the presence of amines and fluoride and iodide ions, but not other halogen ions, in solution. DTzG-DCV and GIDTz-DCV underwent a quick and high-yield reaction with n-butylamine to give imine derivatives, accompanied by PL color changes. Similar color changes were observed even in the solid state with n-butylamine and n-hexylamine. In contrast, reactions with secondary and tertiary alkylamines caused no obvious changes in PL color. The color changes are visible to the naked eye under irradiation with a portable UV lamp at 365 nm, and thus DTzG-DCV and GIDTz-DCV can be used for the quick and selective sensing of primary amines.