Amino Acid Schiff Base Research Articles

Punica granatum pericarp extract catalyzed green chemistry approach for synthesizing novel ligand and its metal(II) complexes: Molecular docking/DNA interactions

The gallic acid (GA) obtained from the ethanolic extract of Pomegranate(Punica granatum) pericarp, was successfully applied as a green and effective natural catalyst for the synthesis of novel quinoline based amino acid Schiff base ligand, L (C16H14N4O3) and its divalent metal complexes (where M = Fe(II), Co(II), Ni(II), Cu(II); L=(E)-2-(((2-hydroxyquinolin-3-yl)methylene)amino)-3-(1H-imidazol-5-yl)propanoic acid) through condensation of 2-hydroxyquinoline-3-carbaldehyde with L-histidine, employing a simple physical grinding technique. The ligand and the complexes denoted as [M(LH2)2] were characterized by advanced spectroscopic and analytical techniques. The configuration of the as synthesized complexes is deduced to be octahedral. The molecular docking experiments were performed by using an Autodock-4 tool to find the binding mode of the metal(II) complexes to B-DNA dodecamer. The metal complex interactions with CT-DNA were studied using spectroscopic techniques, viscosity analysis and thermal denaturation method. In UV-visible irradiation with pUC19 DNA the photo-induced cleavage studies interpreted the photonuclease characteristics of the metal(II) complexes.

New Amino Acid Schiff Bases as Anticancer Agents via Potential Mitochondrial Complex I-Associated Hexokinase Inhibition and Targeting AMP-Protein Kinases/mTOR Signaling Pathway.

Two series of novel amino acid Schiff base ligands containing heterocyclic moieties, such as quinazolinone 3–11 and indole 12–20 were successfully synthesized and confirmed by spectroscopic techniques and elemental analysis. Furthermore, all compounds were investigated in silico for their ability to inhibit mitochondrial NADH: ubiquinone oxidoreductase (complex I) by targeting the AMPK/mTOR signaling pathway and inhibiting hexokinase, a key glycolytic enzyme to prevent the Warburg effect in cancer cells. This inhibitory pathway may be an effective strategy to cause cancer cell death due to an insufficient amount of ATP. Our results revealed that, out of 18 compounds, two (11 and 20) were top-ranked as they exhibited the highest binding energies of −8.8, −13.0, −7.9, and −10.0 kcal/mol in the docking analysis, so they were then selected for in vitro assessment. Compound 11 promoted the best cytotoxic effect on MCF-7 with IC50 = 64.05 ± 0.14 μg/mL (0.135 mM) while compound 20 exhibited the best cytotoxic effect on MDA-231 with IC50 = 46.29 ± 0.09 μg/mL (0.166 mM) Compounds 11 and 20 showed significant activation of AMPK protein and oxidative stress, which led to elevated expression of p53 and Bax, reduced Bcl-2 expression, and caused cell cycle arrest at the sub-G0/G1 phase. Moreover, compounds 11 and 20 showed significant inhibition of the mTOR protein, which led to the activation of aerobic glycolysis for survival. This alternative pathway was also blocked as compounds 11 and 20 showed significant inhibitory effects on the hexokinase enzyme. These findings demonstrate that compounds 11 and 20 obeyed Lipinski’s rule of five and could be used as privileged scaffolds for cancer therapy via their potential inhibition of mitochondrial complex I-associated hexokinase.

Reduced Amino Acid Schiff Base‐Iron(III) Complexes Catalyzing Oxidation of Cyclohexane with Hydrogen Peroxide

AbstractThe reduced amino acid Schiff base ligands have been prepared and were coordinated with ferric chloride to generate the iron(III) complexes. The ligands and complexes have been characterized using FT‐IR, UV‐vis, elemental analysis, ICP‐AES analysis, mass spectra etc. After the structural characterization, these complexes were applied for the oxidation of cyclohexane using hydrogen peroxide as the oxidant under mild conditions. The activity tests showed that the L‐phenylalanine‐derived reduced Schiff base iron(III) complex(Ph−FeCl) afforded the highest yield of cyclohexanol and cyclohexanone(total yield up to 23.2 %). Notably, the Ph−FeCl complex catalyzes the reaction via a heterogeneous approach, allowing the complex to be separated and recycled conveniently after the oxidation reaction. Besides, the Ph−FeCl catalyst can also be extended for the selective oxidation of other alkanes and aromatics into alcohols, ketones and phenols etc. Finally, the reaction mechanism of cyclohexane oxidation on the iron(III) complex was proposed as well by the free radical inhibitors and EPR study of active intermediates.

Crystal structure and SOD activity of a hybrid lysozyme including an amino acid Schiff base copper complex

Crystal structure and SOD activity of a hybrid lysozyme including an amino acid Schiff base copper complex

Enhanced enantioselectivity in heterogeneous manganese-catalyzed asymmetric epoxidation with nanosheets modified amino acid Schiff bases as ligands by modulating the orientation and the arrangement order

Catalytic enantioselective epoxidation of olefins plays an important role in the production of optically-active epoxy. Transition-metal complexes prove efficient for the catalytic epoxidation of un-functionalized olefins by employing privileged chiral ligands with rotational symmetry and bulky substituents, which usually require complicated multistep synthesis and are often very expensive. Here, this work proposes an efficient strategy to promote the enantioselectivity of Mn(III)-catalyzed indene epoxidation, which simply utilizes the nanosheets of layered double hydroxides (LDHs) to modify α-amino acid derivatives as chiral ligands, achieving an enantioselectivity of more than 91.0%, much higher than that (<35%) in the previous reports using chiral ligands without any rotational-symmetry. By virtue of “flexible” interlayer spaces of LDHs, intercalated L-tert-leucine, L-valine, L-leucine, and L-phenylalanine anions have further been derived in situ to L-tert-leucine, L-valine, L-leucine, and L-phenylalanine Schiff base anions. Over the Mn(III) coordinated with L-phenylalanine Schiff base anion intercalated LDHs, an indene conversion of 81.0 ± 1.0%, a chem-selectivity of 89.0 ± 1.0%, and an enantiomeric excesses (ee) value of 94.5 ± 0.5% for (1S,2R)-1,2-epoxyindane have been afforded. The spatial effects of LDH nanosheets on the enantioselectivity have been investigated, focusing on the interlayer orientation and arrangement order of intercalated amino acid derivative anions. The strategy has been proved valid for the epoxidation of functionalized olefins, which is more challenging, including allylic alcohols, chalcone, and chromene derivatives.

Weakly Non-Covalent Docking of Amino-Acid Schiff Base Zn(II) Complex to Lysozyme

Artificial metal enzymes that combine proteins with synthesized unnatural metal complexes as cofactors are attracting attention. The preparation of artificial metal enzymes not only clarifies the behavior of metal ions in biology, but also leads to the development of synthetic chemistry fields such as the discovery of new catalytic reactivity and substrate selectivity that are not observed in nature. In addition, a certain Schiff base zinc (II) complex is known to exhibit antioxidant and anticancer activity, too. Therefore, in this study, we investigated a rapid synthesis method of two known amino acid Schiff base zinc (II) complexes using microwave method and the complexation of zinc (II) complex with chicken egg white lysozyme, which is a relatively low molecular weight protein. Furthermore, investigation of weakly non-covalent intermolecular interaction features between the zinc (II) complexes and lysozyme was also carried out using some spectroscopic measurements.

Mixed Ligand Oxovanadium (IV) Complexes of 5,6-Dimethyl-1,10-phenanthroline and Amino Acid Schiff Bases Containing Salicylaldehyde: Synthesis and Characterization with Antibacterial Properties

Mixed Ligand Oxovanadium (IV) Complexes of 5,6-Dimethyl-1,10-phenanthroline and Amino Acid Schiff Bases Containing Salicylaldehyde: Synthesis and Characterization with Antibacterial Properties

Structure explication, biological evaluation, DNA interaction, electrochemistry and antioxidant activity of iron (II) tri- and tetra-dentate Schiff base amino acid complexes

Structure explication, biological evaluation, DNA interaction, electrochemistry and antioxidant activity of iron (II) tri- and tetra-dentate Schiff base amino acid complexes

Elucidation of DNA binding interaction of new Cu(II)/Zn(II) complexes derived from Schiff base and L-tryptophan amino acid: a multispectroscopic and molecular docking approach.

Herein, we describe the synthesis, structural elucidation, and DNA interaction of newly synthesized Cu(II) and Zn(II) complexes, i.e., [Cu(SB)(L-trp)(H2O)2]NO3 (1) and [Zn(SB)(L-trp)(H2O)2]NO3 (2) (SB = Schiff base obtained from the reaction between o-vanillin and 2-amino-2-methylpropane-1,3-diol; L-trp = L-tryptophan). From the analysis, a six-coordinated environment around the Cu(II) or Zn(II) center is proposed. The ability of the complexes to bind with calf thymus DNA was examined by optical spectroscopy (UV-vis titrations and steady-state fluorescence emission) and viscosity measurements. The vivid experimental results revealed that complexes 1 and 2 avidly bind to DNA through surface and groove binding modes, albeit with dissimilar intrinsic binding constants (1.54 × 104 and 1.36 × 104 M-1 for 1 and 2, respectively). Both complexes can displace ethidium bromide (EB) to some extent from the intercalated EB-DNA system, resulting in fluorescence quenching. Additional experiments such as [Fe(CN)6]4--induced quenching and thermal melting confirmed the electrostatic and groove binding mode. Furthermore, molecular docking studies verified that both complexes locate in the DNA minor groove by surface binding and were stabilized through weak intermolecular forces. The binding affinity of the lowest energy docked pose was found to be -5.37 kcal/mol for complex 1 and - 5.18 kcal/mol for complex 2. The present work is expected to pave the way for the synthesis of DNA-targeting Cu(II)/Zn(II) metal complexes for the development of chemotherapeutic agents.

Preferential intermolecular interactions in a racemic mixture of amino acid Schiff base, conformational structures in solid state, and DFT studies

In this work, we report the green synthesis of a Shiff base [N-(2-hydroxy-1-naphthylidene)-l-phenylalanine (1)] derived from an α-amino acid through an ultrasound-assisted synthesis method with excellent chemical yield in a short period of time.

Synthesis, Characterization, Antimicrobial and DNA Binding Studies of a Tetradentate N2O2 Amino Acid Schiff Base and Its Coordination Compounds

Aminoethanoic acid undergoes condensation with 1,4-benzenedicarboxaldehyde to form an O, N, N, O donor Schiff base, N,N'-di(carboxymethylene) terephthalaldehyde, Ligand L. Coordination compounds of this Schiff base using Ni (II), Cu (II), VO (IV) and Co (II) were then obtained in-situ. The Schiff base and the complexes were evaluated for their antimicrobial and DNA binding abilities. Molecular docking studies of the ligand and synthesized compounds were also carried out. Evidence for the formation of the Schiff base coordination compounds and the coordinating atoms was obtained from 1H NMR, infrared and ultraviolet spectral data, EDX, EDTA complexometric titration and magnetic susceptibility measurement. The results obtained are consistent with octahedral geometry for Ni (II) complex, the metal ion coordinating to one molecule of Ligand L and with additional coordination with two oxygen atoms of two molecules of the solvent. A square-planar geometry was suggested for both Co (II), and Cu (II) complexes and a five-coordinate, square pyramidal geometry for the VO (IV) complex. The results further indicated that the carboxylic acid of Ligand L was not deprotonated both in the free base and also the complexes. In addition, the results showed that Compound 2 elicited the best antimicrobial activity potential. Generally, the compounds exhibited considerable good affinity to CT-DNA.

Synthesis and characterization of amino acid Schiff base and its copper (II) complex and its antimicrobial studies

A highly novel water-soluble copper (II) complex is prepared from freshly synthesized quite handy Schiff base amino acid ligands. To substantiate the fact that Schiff base is normally referred to those compounds which are being used as ligands to form coordination complexes with metal ions, in this work a new series of Schiff base has been produced by the condensation of salicylaldehyde and amino acid namely alanine. Thus derived ligand and its relative copper metal complex were characterized by UV–Visible and FT-IR and NMR analysis. Based on the results of spectral analysis, the structures of the ligand and the complex were deduced. The purity of the products were examined through Thin Layer Chromatography (TLC). The antimicrobial properties of both the ligands and its corresponding copper complex has been deduced against human pathogens namely E-Coli, Bacillus Subtilis, Candida Albicans etc. A satisfactory inhibition caused by the copper complex over the ligand is verified and reported. The spectral analysis and applications of Schiff base metal complex is encouraging and the related investigation could be further extended to anti tumor as well as catalytic activities.

Studies of DNA Linking Capacity Form, Spectroscopic, and Valuation of Hydrophobicity, cytotoxicity and Antibacterial activities for Some New Fe(II) Complexes Bearing ONN Donors Amino Acid Schiff bases

Studies of DNA Linking Capacity Form, Spectroscopic, and Valuation of Hydrophobicity, cytotoxicity and Antibacterial activities for Some New Fe(II) Complexes Bearing ONN Donors Amino Acid Schiff bases

Cashew nutshell liquid catalyzed green chemistry approach for synthesis of a Schiff base and its divalent metal complexes: molecular docking and DNA reactivity

Cashew Nut Shell Liquid (CNSL) anacardic acid was used, for the first time, as a green and natural effective catalyst for the synthesis of a quinoline based amino acid Schiff base ligand from the condensation of 2-hydroxyquinoline-3-carbaldehyde with l-tryptophan via solvent-free simple physical grinding technique. The use of the nontoxic CNSL natural catalyst has many benefits over toxic reagents and the desired product was obtained in high yield in a short reaction time. The procedure employed is simple and does not involve column chromatography. Moreover, a series of metal(II) complexes (metal = iron(II), cobalt(II), nickel(II), and copper(II)) supported by the synthesized new quinoline based amino acid Schiff base ligand (L) has been designed and the compositions of the metal(II) complexes were examined by various analytical techniques. The findings imply that the 2-hydroxyquinoline-3-carbaldehyde amino acid Schiff base (L) serves as a dibasic tridentate ONO ligand and synchronizes with the metal(II) in octahedral geometry in accordance with the general formula [M(LH)2]. Molecular docking study of the metal(II) complexes with B-DNA dodecamer has revealed good binding energy. The conductivity parameters in DMSO suggest the existence of nonelectrolyte species. The interaction of these metal complexes with CT-DNA has shown strong binding via an intercalative mode with a different pattern of DNA binding, while UV-visible photo-induced molecular cleavage analysis against plasmid DNA using agarose gel electrophoresis has revealed that the metal complexes exhibit photo induced nuclease activity.

Aminoacid Schiff base Fabricated Glassy carbon Electrode for Efficient Sensing of Zinc, Copper, Mercury ions in Water

The Schiff base like 5-bromo-2-hydroxybenzylideneamino)-3-hydroxypropanoate from 2-Amino-3-hydroxypropionicacid and5-bromo-2-hydroxybenzaldehyde. The prepared aminoacid schiff base characterized by Infrared spectroscopy and Nuclear magnetic resonance spectroscopy. The aminoacid schiffbase fabricated modified glassy carbon electrode have been evaluated by electrochemical techniques like, cyclic voltammetry (CV) and square-wave anodic stripping voltammetry (SWASV). The optimized working conditions of aminoacid schiffbase glassy carbon electrode have been evaluated by the consequences of concentration, PH values, different supporting electrolytes and electrode potential. The heavy metal ions have been detected using electrochemical studies.

Trinuclear nickel(II) amino acid Schiff base complex containing phenolato and acetato bridges: Structural and functional resemblance of urease

A novel phenolato and acetato bridged trinuclear Ni(II) complex [Ni3L2] was synthesized by the reaction between the amino acid Schiff base, N-o-vanillylidene-l-histidine(L) and Ni(OAc)2·2H2O. Single crystal X-ray analysis reveals that the trinuclear structure of Ni3L2 is built by linking two terminal NiN2O4 cores with one NiO6 centre core (NiN2O4⋯NiO6⋯NiN2O4) and each Ni(II) ion exists in an octahedral environment. Variable-temperature magnetic susceptibility data represent the antiferromagnetic interactions of the Ni3L2 mediated by a single Ni-O-Ni bridge. The bond length and bond angles around each terminal nickel centre match the nickel centre in urease enzyme of native bacteria Klebsiella aerogenes, Bacillus pasteurii and Helicobacter pylori. The catalytic activity of Ni3L2 on the hydrolysis of urea into ammonia and carbon dioxide was established by the absorption spectral method. The urea binding propensity of the nickel complex Ni3L2 was compared with jack bean urease by using molecular docking studies.

Synthesis of Amino Acid Schiff Base Nickel (II) Complexes as Potential Anticancer Drugs In Vitro.

Three hexacoordinated octahedral nickel (II) complexes, [Ni (Trp-sal) (phen) (CH3OH)] (1), [Ni (Trp-o-van) (phen) (CH3OH)]•2CH3OH (2), and [Ni (Trp-naph) (phen) (CH3OH)] (3) (where Trp-sal = Schiff base derived from tryptophan and salicylaldehyde, Trp-o-van = Schiff base derived from tryptophan and o-vanillin, Trp-naph = Schiff base derived from tryptophan and 2-hydroxy-1-naphthaldehyde, phen = 1, 10-phenanthroline), have been synthesized and characterized as potential anticancer agents. Details of structural study of these complexes using single-crystal X-ray crystallography showed that distorted octahedral environment around nickel (II) ion has been satisfied by three nitrogen atoms and three oxygen atoms. All these complexes displayed moderate cytotoxicity toward esophageal cancer cell line Eca-109 with the IC50 values of 23.95 ± 2.54 μM for 1, 18.14 ± 2.39 μM for 2, and 21.89 ± 3.19 μM for 3. Antitumor mechanism studies showed that complex 2 can increase the autophagy, reactive oxygen species (ROS) levels, and decrease the mitochondrial membrane potential remarkably in a dose-dependent manner in the Eca-109 cells. Complex 2 can cause cell cycle arrest in the G2/M phase. Additionally, complex 2 can regulate the Bcl-2 family and autophagy-related proteins.

Antioxidant and Cytotoxic Activity Studies in Series of Higher Amino Acid Schiff Bases

In this work, the antioxidant activity of the higher amino acid Schiff bases, which were prepared as the monosodium salts (1a–3a) and the neutral forms (1b–3b) was determined by DPPH scavenging assay. In pure MeOH solution, the scavenging ability of Schiff bases 1a-3a were higher than 1b-3b, but lower than ascorbic acid. The activity followed the order 3 (a,b) &amp;gt; 2 (a,b) &amp;gt; 1 (a,b). On the other hand, Schiff bases 2a and 3a behaved as the most effective scavengers of the DPPH radical in methanol-water mixture (v:v, 1:3). And, they were found to be have lower SC50 values in this mixture compared to pure methanol. In vitro cytotoxicity of these Schiff bases was studied against human cervical cancer cells (HeLa), human breast adenocarcinoma cells (MCF-7), and human normal embryonic kidney cells (HEK293). For HeLa cell line, Schiff bases 1a-3a exhibited a litttle high activity than 1b, but very low activity than doxorubicin. Schiff bases 2b and 3b had no cytotoxicity against HeLa cell. For MCF-7 cell line, Schiff bases 1a, 3a, 1b and 3b nearly were inactive at 100 µM, whereas 2a increased cell proliferation in the all tested concentration range. Differently, Schiff base 2b showed the highest cytotoxicity and killed 90 percent of MCF-7 cells at concentration of 100 µM. For HEK-293, doxorubicin was strongly cytotoxic. Despite this, Schiff bases 1a, 3a and 3b were inactive, whereas the others showed little weak toxicity.

Water-soluble Cu(II)-complexes of Schiff base amino acid derivatives as biological reagents and sufficient catalysts for oxidation reactions

Two novel water-soluble Cu(II) complexes (Cu-PSA and Cu-PSL) are synthesized from easily accessible Schiff base amino acid ligands (HPSA and HPS), as sodium sulfonate salts, obtained from D,L-phenylalanine and D,L-leucine, respectively. Their chemical composition is confirmed using various spectroscopic analyses (NMR, UV–vis, IR and mass spectroscopies, CHN micro-analyses, conductivities, TGA, and magnetism). The effect of sodium sulfonate group (Na+ SO3− group) on the chemical behavior of both Cu-PSA and Cu-PSL complexes is studied catalytically and biologically. Catalytically, Cu-PSA and Cu-PSL exhibit high reactivity in the (ep)oxidation of 1,2-cyclooctene and benzyl alcohol in polar reaction media, (acetonitrile or water) at 80 °C, under homogeneous reaction condition. Biologically, the Cu-complexes and their ligands (HPSA and HPS) are tested for antimicrobial activity against some pathogens strains. Both Cu-complexes reveal higher performance than their corresponding ligands. Cu-PSA and Cu-PSL complexes are also examined for ctDNA-interaction, which studied using various techniques including spectroscopy, viscosity and gel-electrophoresis. Despite, their low lipophilicity due to the sodium sulfonate group (salting group), they show potentially high electrostatic interaction with ctDNA. The binding potential of these compounds is also investigated by molecular docking showing the role of the central metal ion (Cu2+) and the salting group in the ctDNA interaction. For anticancer reactivity, both ligands (HPSA, HPSL), and their complexes (Cu-PSA or Cu-PSL) are examined against hepatocellular carcinoma (HepG2) cell line, breast carcinoma (MCF7) cell line and colon carcinoma (HCT-116) cell line. The obtained results are encouraging and after optimization the Cu-complexes could be potentially anticancer drug candidates.

Transition metal complexes constructed by pyridine–amino acid: fluorescence sensing and catalytic properties

Four amino acid Schiff base complexes—one with a 3D network structure ({[Cd2(PYSA)2(H2O)]·3H2O}n (1)) and the other three with a supramolecular network structure {[Co(PYSA) (H2O)2]·H2O}n (2), {([Zn(PYSA)(H2O)2]·H2O}n (3), {[Mn(PYSA)(H2O)2]·H2O}n (4)), (PYSA = (S-2-(pyridine-4-ylmethylamino) succinic acid)—were successfully obtained under hydrothermal conditions. Among the four complexes, photoluminescence analysis revealed that complex 1 exhibited high selectivity and sensitivity in the detection of iron ions. In particular, it was able to qualitatively and quantitatively detect iron ions at low concentrations without interference from other ions. With a Fe3+ concentration of 0.01 mol/L, the detection limit was 0.81 μM, Ksv = 2.46 × 104 L/mol. In addition, complex 2 exhibited excellent catalytic performance toward 4-nitrophenol (4-PNP). Four amino acid Schiff base complexes 1–4 were synthesized by a hydrothermal method. Among the four, complex 1 exhibited good fluorescence sensing performance in the detection of Fe3+ in water. In addition, the catalytic activity of complex 2 for 4-PNP was preliminarily investigated, which showed an ability to reduce 4-PNP to 4-PAP.