Oxidovanadium(V) Schiff Base Complexes Derived from Chiral 3-amino-1,2-propanediol Enantiomers: Synthesis, Spectroscopic Studies, Catalytic and Biological Activity.

Oxidovanadium(V) complexes, [(+)VOL1-5] and [(-)VOL1-5], with chiral tetradentate Schiff bases, which are products of monocondensation of S(‒)-3-amino-1,2-propanediol or R(+)-3-amino-1,2-propanediol with salicylaldehyde derivatives, have been synthesized. Different spectroscopic methods, viz. 1H and 51V NMR, IR, UV-Vis, and circular dichroism, as well as elemental analysis, have been used for their detailed characterization. Furthermore, the epoxidation of styrene, cyclohexene, and two monoterpenes, S(‒)-limonene and (‒)-α-pinene, using two oxidants, aqueous 30% H2O2 or tert-butyl hydroperoxide (TBHP) in decane, has been studied with catalytic amounts of all complexes. Finally, biological cytotoxicity studies have also been performed with these oxidovanadium(V) compounds for comparison with cis-dioxidomolybdenum(VI) Schiff base complexes with the same chiral ligands, as well as to determine the cytoprotection against the oxidative damage caused by 30% H2O2 in the HT-22 hippocampal neuronal cells in the range of their 10-100 µM concentration.

Synthesis, antimicrobial activity, antioxidant activity and molecular docking of novel chitosan derivatives containing glycine Schiff bases as potential succinate dehydrogenase inhibitors.

Succinate dehydrogenase (SDH) is an important inner mitochondrial membrane-bound enzyme involved in redox reactions during the tricarboxylic acid cycle. Therefore, a series of novel chitosan derivatives were designed and synthesized as potential microbicides targeting SDH and precisely characterized by FTIR, 1H NMR and SEM. Their antifungal and antibacterial activities were evaluated against Botrytis cinerea, Fusarium graminearum, Staphylococcus aureus and Escherichia coli. The bioassays revealed that these chitosan derivatives exerted significant antifungal effects, with four of the compounds achieving 100 % inhibition of Fusarium graminearum merely at a concentration of 0.5 mg/mL. Additionally, CSGDCH showed 79.34 % inhibition of Botrytis cinerea at a concentration of 0.1 mg/mL. In vitro antibacterial tests revealed that CSGDCH and CSGDBH have excellent Staphylococcus aureus and Escherichia coli inhibition with MICs of 0.0156 mg/mL and 0.03125 mg/mL, respectively. Molecular docking studies have been carried out to explore the binding energy and binding mode of chitosan and chitosan derivatives with SDH. The analyses indicated that chitosan derivatives targeted the active site of the SDH protein more precisely, disrupting its normal function and ultimately repressing the growth of microbial cells. Furthermore, the chitosan derivatives were also evaluated biologically for antioxidation, and all of these compounds had a greater degree of reducing power, superoxide radical, hydroxyl radical and DPPH-radical scavenging activity than chitosan. This research has the potential for the development of agricultural antimicrobial agents.

Synthesis of new quaternized chitosan Schiff bases and their N-alkyl derivatives as antimicrobial and anti-biofilm retardants in membrane technology.

New quaternized salicylidene chitosan Schiff bases (QSCSBs) and their N-octyl derivatives (OQCs) have been synthesized and characterized, aiming to develop innovative antimicrobial and anti-biofilm agents. This research holds immense potential, as these compounds could be utilized as anti-biofouling additives in membrane technology in the future. The synthesis involved the modification of low molecular-weight-chitosan (LMC) through simultaneous Schiff base formation and quaternization processes to create QSCSBs. Subsequently, QSCSBs were catalytically reduced to form quaternized N-benzyl chitosan (QBCs) intermediates, which then underwent nucleophilic substitution reactions affording N-octyl quaternized chitosans (OQCs). Characterization techniques such as elemental, spectral, and microscopic analyses were used to confirm the successful synthesis of these materials. As membrane technology relies on surface charge, QSCSBs and OQCs with large zeta potentials could be used as positively charged additives. Moreover, SEM image revealed the regular distribution of pores and voids across the additives' surfaces raises intriguing questions about their implications for membrane performance. Meanwhile, the superior antibacterial and antibiofilm potential of these materials, particularly QSCSB2 and OQC2, indicate that the utilization of these compounds as anti-biofouling additives in membrane technology could significantly improve the performance and longevity of membranes used in various applications such as water treatment and desalination.

New penta-Coordinated Cadmium(II) Complexes: Synthesis, Characterization, Thermal, Antimicrobial, Antioxidant and Cytotoxicity Properties.

In this paper, a new tridentate Schiff base ligand (L) with nitrogen donor atoms and its cadmium(II) complexes with the general formula of CdLX2 (X=Cl-, Br-, I-, SCN-, N3 -, NO3 -) have been synthesized and characterized by physical and spectral (FT/IR, UV-Vis, Mass, and 1H, 13C NMR spectroscopies) methods. Also nano-structured cadmium chloride and bromide complexes were synthesized by sonochemical method and then used to prepare nanostructured cadmium oxide confirmed by XRD and SEM techniques. Thermal behavior of the compounds was studied in the temperature range of 25 to 900 °C under N2 atmosphere at a heating rate of 20 °C/ min. Moreover, thermo-kinetic activation parameters of thermal decomposition steps were calculated according to the Coats-Redfern relationship. Antimicrobial activities of the synthesized compounds against two gram-positive and two gram-negative bacteria such as Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and two fungi of Candida albicans and Aspergillus niger were investigated by well diffusion method. SEM technique was used to monitor the morphological changes of the bacteria treated with the compounds. The 2,2-Diphenyl-1-picrylhydrazyl(DPPH) and the ferric reducing antioxidant power (FRAP) methods were used to evaluate the antioxidant ability of the ligand and its cadmium(II) complexes. In final, the cytotoxicity properties of the ligand and some cadmium(II) complexes against PC3 cancer cells were evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) bioassay and nitric oxide (NO) level measurement. The morphological changes of prostate cancer (PC3) cells due to treatment with the ligand and its complexes confirmed their anticancer effectiveness.

Synthesis and Antifungal Properties of 1,2,4-Triazole Schiff Base Agents Based on a 3D-QSAR Model.

Based on our previous research, a 3D-QSAR model (q2=0.51, ONC=5, r2=0.982, F=271.887, SEE=0.052) was established to predict the inhibitory effects of triazole Schiff base compounds on Fusarium graminearum, and its predictive ability was also confirmed through the statistical parameters. According to the results of the model design, 30 compounds with superior bioactivity compared to the template molecule 4 were obtained. Seven of these compounds (DES2-6, DES9-10) with improved biological activity and readily available raw materials were successfully synthesized. Their structures were confirmed through HRMS, NMR, and single crystal X-ray diffraction analysis (DES-5). The bioactivity of the final products was investigated through an in vitro antifungal assay. There was little difference in the EC50 values between the experimental and predicted values of the model, demonstrating the reliability of the model. Especially, DES-3 (EC50=9.915 mg/L) and DES-5 (EC50=9.384 mg/L) exhibited better inhibitory effects on Fusarium graminearum compared to the standard drug (SD) triadimenol (EC50=10.820 mg/L). These compounds could serve as potential new fungicides for future research. The interaction between the final products and isocitrate lyase (ICL) was investigated through molecular docking. Compounds with R groups that have a higher electron-donating capacity were found to be biologically active.

Synthesis, Characterization, Anti-Glycation, and Anti-Oxidant Activities of Sulfanilamide Schiff Base Metal Chelates.

The current study reports synthesis, structure establishment, anti-glycation, and anti-oxidant activities of ligand 4-[(2-hydroxynaphthalene-1-ylmethylene)-amino]-benzenesulfonamide (L) and its coordination compounds with Mn(II), Co(II), Ni(II), Cu(II), and Zn(II) metal ions. The analytical techniques used (UV-Vis, FT-IR, CHN/S) confirmed the bidentate nature of the ligand, coordinating via O and N atoms in 2:1 ligand-to-metal ratio. The TG/DTA anylsis displayed that these compounds are thermally stable. Furthermore, the synthesized compounds were evaluated for their anti-glycation and antioxidant potential and showed significant activities with IC50 values range 184.11-386.34 µM and 37.05-126.27 µM, respectively. The Mn (IC50 = 184.11 ± 2.11 µM), Ni (IC50 = 211.26 ± 1.46 µM), Cu (IC50 = 254.56 ± 1.16 µM), and Zn (IC50 = 276.43 ± 2.14 µM) metal complexes exhibited substantial anti-glycation activity and comparatively better activity than the standard rutin (IC50 = 294.4 ± 1.50 µM), whereas Zn complex (IC50 = 37.05 ± 1.53 µM) also showed better DPPH radical scavenging activity than the standard tert-butyl-4-hydroxyanisole (IC50 = 44.7 ± 1.21 µM).

Novel amino acid Schiff base Zn(II) complexes as new therapeutic approaches in diabetes and Alzheimer's disease: Synthesis, characterization, biological evaluation, and molecular docking studies.

Schiff bases are compounds that have gained importance in the paint industry due to their colorful nature and in the field of chemistry and biochemistry due to their biological activities. Various biological applications of Schiff bases, such as antitumor, antifungal, antibacterial, antioxidant, antituberculosis, and anthelmintic, have been widely studied. Within the scope of the study, 5-bromo-2-hydroxybenzaldehyde and amino acid methyl esters (isoleucine, phenylalanine, and methionine) and amino acid Schiff bases were synthesized first. The synthesis of the new Zn(II) complexes of these Schiff bases was carried out by the reaction of synthesized Schiff bases and Zn(OAc)2 ·2H2 O. The structures of the synthesized complexes were elucidated using elemental analysis, Fourier transform infrared, nuclear magnetic resonance, UV-visible, and thermal analysis spectroscopy techniques. These synthesized salts were found to be effective inhibitor compounds for the α-glycosidase, and acetylcholinesterase enzyme with Ki values in the range of 30.50 ± 3.82-38.17 ± 6.26 µM for α-glycosidase, 3.68 ± 0.54-10.27 ± 1.68 µM for butyrylcholinesterase, and 6.26 ± 0.83-15.73 ± 4.73 µM for acetylcholinesterase, respectively.

Preparation and characterization of Gum Arabic Schiff's bases based on 9-aminoacridine with in vitro evaluation of their antimicrobial and antitumor potentiality.

The conjugation between drug and biopolymers through an easily hydrolysable bond such as ester linkage, disulfide linkage, or imine-bond have been extensively employed to control the drug release pattern and improve its bioavailability. This work described the conjugation of 9-aminoacridine (9-AA) to Gum Arabic (GA) via Schiff's base, as a pH-responsive bond. First, GA was oxidized to Arabic Gum dialdehyde (AGDA), then a different amount of 9-AA (10, 25, and 50 mg 9-AA) was coupled to defined amount of AGDA, the coupling was confirmed by elemental analysis and different spectroscopic tools. In addition, the physical features of Schiff's base conjugates including surface morphology, thermal stability, and crystalline structure were examined. The thermogravimetric analysis revealed that the incorporation of 9-AA slightly improved the thermal stability. The coupling of 9-AA to AGDA dramatically enhanced its in vitro antimicrobial and antitumor activities. All conjugates exhibited broad-spectrum activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis, and Candida albicans. Moreover, AGA 25 and AGA 50 demonstrated promising capability to suppress the proliferation of human colon cancer cell line (Caco-2), with IC50 190.10 and 180.80 µg/mL respectively.

Ortho-hydroxy bioactive schiff base compounds: Design, comprehensive characterization, photophysical properties and elucidation of antimicrobial and mutagenic potentials.

Preparation and comprehensive characterization of three Schiff base ligands; with trimethoxy substitution (1E,1'E)-N,N'-(naphthalene-1,5-diyl)bis(1-(3,4,5-trimethoxyphenyl)methanimine, 1, with ortho-hydroxy substitution 6,6'-((1E,1'E)-(naphthalene-1,5-diylbis(azaneylylidene))bis(methaneylylidene))bis(2-methoxyphenol), 2 and 3,4-bis(((E)-2-hydroxy-3-methoxy benzylidene)amino)benzoicacid, 3 and their Ni(II), Cu(II), Co(II), Zn(II), Fe(II), Mn(II) complexes have been reported. Their spectral properties were studied in solution and solid-state by a combination of different analytical techniques; FT-IR spectroscopy, 1H NMR and 13C NMR spectroscopy, elemental analysis and thermal analysis. Diamagnetic and paramagnetic natures of the complexes were also determined by magnetic susceptibility measurements in solid-state. Promising photophysical properties were observed as; Amax. were recorded at 226 nm for 2; at 795 nm for 2-Ni, at 782 nm for 2-Cu, at 784 nm for 2-Co, at 702 nm for 2-Zn, at 784 nm for 2-Fe, at 702 nm for 2-Mn and at 289 nm for 3, at 786 nm for 3-Ni, at 797 nm for 3-Cu, at 746 nm for 3-Co, at 794 nm for 3-Zn, at 699 nm for 3-Fe, at 781 nm for 3-Mn ; and Imax were also recorded at; 380, 490, 725 nm for 2 and 2-Metal; 375 nm, 510 nm, 725 nm for 3 and 3-Metal when excitated at 220 nm. Antibacterial activities against different microorganisms; Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Klebsiella pneumoniae ATCC 70603, Staphylococcus aureus ATCC 43,300 (MRSA), Salmonella enteritidis ATTC 13076, Sarcina lutea ATCC 9341, Bacillus cereus ATTC 11778, and antifungal activities against Candida albicans NRRL Y-417 of the compounds 1, 2, 3, 2-Cu, 2-Fe, 3-Zn, 3-Fe were determined. Mutagenic properties of the compounds were also studied and according to the results 2-Cu and 3 have been found non-mutagenic in Ames test but also they have strong antimicrobial potential against pathogen microorganisms. For 2-Cu MIC values were ranging between 0.39 and 0.024 mg/ml and the lowest minimum inhibitory concentration (0.024 mg/ml) was determined against E. coli. The 3 numbered compound revealed strong antimicrobial activity at doses of ranging between 0.39 and 0.097 mg/ml and E. coli was the most sensitive bacterium against this chemical.

Syntheses, Crystal Structures, and Antibacterial Activity of New Tetranuclear Zinc(II) Complexes with Schiff Base Ligands.

Two new tetranuclear zinc(II) complexes, [Zn4(L1)2(µ2-η1:η1-CH3COO)4(µ1,1-N3)2] (1) and [Zn4(L2)4(CH3CH2OH)(H2O)] (2), where L1 and L2 are the deprotonated forms of 4-fluoro-2-((pyridin-2-ylmethylimino)methyl)phenol (HL1) and 4-fluoro-2-((2-(hydroxymethyl)phenylimino)methyl)phenol (H2L2), have been synthesized and characterized by elemental analysis, IR and UV-vis spectroscopy, and single crystal X-ray diffraction. X-ray crystal structural study indicated that the distances between the adjacent Zn atoms are 3.160(1)-3.353(1) Å in 1 and 3.005(1)-3.168(1) Å in 2. All zinc atoms in 1 are pentacoordinated in trigonal bipyramidal geometry, and those in 2 are in square pyramidal and octahedral geometry. The complexes and the Schiff bases were assayed for antibacterial activities against three Gram-positive bacterial strains (B. subtilis, S. aureus, and St. faecalis) and three Gram-negative bacterial strains (E. coli, P. aeruginosa, and E. cloacae) by MTT method.

Synthesis, Characterization and Crystal Structures of Zinc(II) and Cobalt(III) Complexes Derived from Tridentate NNO- and NON- Schiff Bases with Antibacterial Activities.

Two new polynuclear zinc complexes [Zn2Br2(L1)2] (1) and [Zn(µ1,5-dca)L2]n (2), and two new mononuclear cobalt(III) complexes [CoL1N3(Brsal)] (3) and [CoL2(HL2)] (4), where L1 = 5-bromo-2-(((2-dimethylamino)ethyl)imino)methyl)phenolate, L2 = 5-bromo-2-(((2-hydroxyethyl)imino)methyl)phenolate, dca = dicyanoamide, Brsal = 5-bromo-2-formylphenolate, have been synthesized and characterized. The complexes were characterized by elemental analyses, IR, UV-Vis spectra, molar conductivity, and single crystal X-ray diffraction. X-ray analysis indicates that the Zn atoms in complex 1 are in distorted square pyramidal coordination, the Zn atoms in complex 2 are in distorted trigonal bipyramidal coordination, and the Co atoms in complexes 3 and 4 are in octahedral coordination. The molecules of the complexes are stacked through π···π interactions and hydrogen bonds. The complexes were assayed for antibacterial activities against three Gram-positive bacterial strains (B. subtilis, S. aureus, and St. faecalis) and three Gram-negative bacterial strains (E. coli, P. aeruginosa, and E. cloacae) by MTT method.

Highly Efficient Multifunctional Organic Photosensitizer with Aggregation-Induced Emission for In Vivo Bioimaging and Photodynamic Therapy.

Photosensitizers play a critical role in photodynamic therapy (PDT). Multifunctional organic nanoparticles (NPs) that possess bright fluorescence in aggregates, high singlet oxygen (1O2) quantum yield, near-infrared (NIR) absorption and emission, large Stokes shift, two-photon bioimaging, specific organelle targeting, high PDT efficiency, as well as good biocompatibility and photostability are ideal candidate photosensitizers for image-guided PDT. Due to its enhanced fluorescence and high 1O2 generation efficiency in aggregate states, photosensitizers with aggregation-induced emission (AIE) characteristics have attracted increasing interest in PDT. In this study, a new AIE-active Schiff base 5-(((5-(7-(4-(diphenylamino)phenyl)benzo[c][1,2,5]thiadiazol-4-yl)thiophen-2-yl)methylene)amino)-3-methylthiophene-2,4-dicarbonitrile (TBTDC) based on a D-A-π-A skeleton has been designed and synthesized, and it can be readily encapsulated by Pluronic F-127 to form uniform nanoparticles. TBTDC NPs exhibit bright NIR emission at 825 nm with a Stokes shift up to 300 nm, impressive two-photon bioimaging capability with tissue penetration deep into 300 µm, high 1O2 generation quantum yield (0.552), specific targeting to lysosome, as well as good biocompatibility and photostability. Furthermore, TBTDC NPs present remarkable cytotoxicity for tumor cells and suppression of tumor growth in nude mice through reactive oxygen species generation upon white light irradiation. These results reveal that TBTDC NPs have great potential to become excellent candidates for multifunctional organic photosensitizers for two-photon bioimaging and image-guided PDT and are promising in future clinical applications.

Synthesis, Spectroscopic Analysis, and in Vitro/in Silico Biological Studies of Novel Piperidine Derivatives Heterocyclic Schiff-Mannich Base Compounds.

In the present study, 3-substitued-4-(4-hydroxybenzylidenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones (S1-8) were synthesized by treating 4-hydroxybenzaldehyde (B) with eight different 3-substitued-4-amino-4,5-dihydro-1H-1,2,4-triazole-5-ones (T1-8) in acetic acid medium, separately. The synthesized Schiff bases (S) were reacted with formaldehyde and secondary amine such as 4-piperidinecarboxyamide to afford novel heterocyclic bases. 3-Substitued-4-(4-hydroxybenzylidenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones (T) were treated with 4-piperidinecarboxyamide in the presence of formaldehyde to synthesize eight new 1-(4-piperidinecarboxyamide-1-yl-methyl)-3-substitued-4-(4-hydroxybenzylidenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones (M1-8). The structure characterization of compounds was carried out using 1 H-NMR, IR, HR-MS, and 13 C-NMR spectroscopic methods. The inhibitory properties of the newly synthesized compounds were calculated against the acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and glutathione S-transferase (GST) enzymes. Ki values were calculated in the range of 20.06±3.11-36.86±6.17 µM for GST, 17.87±2.91-30.53±4.25 µM for AChE, 9.08±0.69-20.02±2.88 µM for BChE, respectively, Besides, IC50 values were also calculated. Best binding scores of -inhibitors against used enzymes were calculated as -12.095 kcal/mol, -12.775 kcal/mol, and -9.336 kcal/mol, respectively. While 5-oxo-triazole piperidine-4-carboxamide moieties have a critical role in the inhibition of AChE and GST enzymes, hydroxy benzyl moiety is important for BChE enzyme inhibition.

Synthesis and Spectroscopic Investigations of Schiff Base Ligand and Its Bimetallic Ag(I) Complex as DNA and BSA Binders.

Generation of well-defined potential metallotherapeutics for cancer treatment, one of the most population-threatening diseases, is challenging and an active area of modern research in view of their unique properties and thus multiple possible pathways of action in cells. Specifically, Schiff base ligands were recognized as very promising building blocks for the construction of stable and active complexes of numerous geometries and topologies. Incorporation of Ag(I) ions allows for the formation of flat complexes with potential unoccupied coordination sites, thus giving rise to specific interactions between the metallotherapeutic and biomolecule of interest. Herein, we present the design, synthesis and characterization of new Schiff base ligand L and its Ag(I) bimetallic complex [Ag2L2]2+ with two planar moieties formed around the metal ions and connected through cyclohexane rings, confirmed by X-ray measurements. The compounds were described in context of their potential use as anticancer drugs through DNA and BSA binding pathways by several spectroscopic methods (CD, UV-Vis, fluorescence). We revealed that both, L and [Ag2L2]2+, interact with similar affinity with CT-DNA (Kb~106 M-1), while they differ in the type and strength of interactions with the model albumin-BSA. [Ag2L2]2+ binds BSA in both a dynamic and static manner with the Ksv = 8.8 × 104 M-1 in the Trp-134 and Trp-213 sites, whereas L interacts with BSA only dynamically (KSV = 2.4 × 104 M-1). This found further confirmation in the CD studies which revealed a reduction in α-helix content in the albumin of 16% in presence of [Ag2L2]2+.

Design, synthesis, and molecular docking study of some 2-((7-chloroquinolin-4-yl) amino) benzohydrazide Schiff bases as potential Eg5 inhibitory agents.

In Search of new microtubule-targeting compounds and to identify a promising Eg5 inhibitory agents, a series of 2-((7-chloroquinolin-4-yl) amino) benzohydrazide Schiff bases molecules (6 a-r) were synthesized using appropriate synthetic method. The synthesized compounds were characterized by using FTIR, Proton NMR, Carbon NMR and mass spectral analysis. All eighteen compounds were evaluated for their Eg5 inhibitory activity. Among the evaluated compounds, only seven compounds are shown inhibitory activity. The results of Steady state ATPase reveled that compounds 6b, 6l and 6p exhibited promising inhibitory activity with IC50 Values of 2.720 ± 0.69, 2.676 ± 0.53 and 2.408 ± 0.46 respectively. Malachite Green Assay results reveled that 6q compound showed better inhibitory activity with IC50 Value of 0.095 ± 0.27. In vitro antioxidant capacity of the synthesized compounds was investigated. A molecular docking studies were performed to evaluate interaction in to binding site of kinesin spindle protein, these interaction influencing may support Eg5 inhibitory activity. The drug like parameters of the eighteen synthesized compounds were also computed using Qikprop software. In conclusion, some of 2-((7-chloroquinolin-4-yl) amino) benzohydrazide Schiff base compounds represent promising drug like agents for discovery of effective anticancer molecules.

Diaminomaleonitrile derivatives as new potential antichagasic compounds: a study of structure-activity relationships.

Background: Schiff bases are synthetically accessible compounds that have been used in medicinal chemistry. Methods & results: In this work, 27 Schiff bases derived from diaminomaleonitrile were synthesized in high yields (80-98%). Molecular docking studies suggested that the Schiff bases interact with the catalytic site of cruzain. The most active cruzain inhibitor, analog 13 (IC50 = 263 nM), was predicted to form an additional hydrophobic contact with Met68 in the binding site of the enzyme. A strong correlation between the IC50 values and ChemScore binding energies was observed (R = 0.99). Kernel-based 2D quantitative structure-activity relationship models for the whole dataset yielded sound correlation coefficients (R2 = 0.844; Q2 = 0.719). Conclusion: These novel and potent cruzain inhibitors are worthwhile starting points in further Chagas disease drug discovery programs.

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.

Synthesis, Structural Investigations, Molecular Docking, and Anticancer Activity of Some Novel Schiff Bases and Their Uranyl Complexes.

Three novel 2-aminopyrazine Schiff bases derived from salicylaldehyde derivatives and their uranyl complexes were synthesized and characterized by elemental analysis, UV-vis, FTIR, molar conductance, and thermal gravimetric analysis (TGA). The proposed structures were optimized using density functional theory (DFT/B3LYP) and 6-311G ∗(d,p) basis sets. All uranyl complexes are soluble in DMSO and have low molar conductance, which indicates that all the complexes are nonelectrolytes. The DNA binding of those Schiff bases and their uranyl complexes was studied using UV-vis spectroscopy, and screening of their ability to bind to calf thymus DNA (CT-DNA) showed that the complexes interact with CT-DNA through an intercalation mode, for which the Kb values ranged from 1 × 106 to 3.33 × 105 M-1. The anticancer activities of the Schiff base ligands and their uranyl complexes against two ovarian (Ovcar-3) and melanoma cell lines (M14) were investigated, and the results indicated that uranyl complexes exhibit better results than the Schiff base ligands. Molecular docking identified the distance, energy account, type, and position of links contributing to the interactions between these complexes and two different cancer proteins (3W2S and 2OPZ).

A chitosan hydrogel sealant with self-contractile characteristic: From rapid and long-term hemorrhage control to wound closure and repair.

Emergent and long-term hemorrhage control is requisite and beneficial for reducing global mortality and postoperative complications (e.g., second bleeding and adverse tissue adhesion). Despite recent advance in injectable hydrogels for hemostasis, achieving rapid gelation, strong tissue-adhesive property and stable mechanical strength under fluid physiological environment is still challenging. Herein, we developed a novel chitosan hydrogel (CCS@gel) via dynamic Schiff base reaction and mussel-inspired catechol chemistry. The hydrogel possessed high gelation rate (<10 s), strong wet adhesiveness, excellent self-healing performance and biocompatibility. More importantly, the CCS@gel exhibited saline-induced contractile performance and mechanical enhancement, promoting its mechanical property in moist internal conditions. In vivo studies demonstrated its superior hemostatic efficacy for diverse anticoagulated visceral and carotid bleeding scenarios, compared to commercialized fibrin glue. The hydrogel-treated rats survived for 8 weeks with minimal inflammation and postoperative adhesion. These results revealed that the promising CCS@gel would be a facile, efficient and safe sealant for clinical hemorrhage control.

Experimental Study on the Raman Spectra of Imine Emulsification with Chemometrics.

In this study, we aimed to investigate imine emulsification using Raman spectroscopy with chemometrics. The imine emulsification samples were obtained by mixing aldehydes and amines in methanol and aqueous methanol. The Raman spectra of the samples were measured over time between 400 and 2300 cm-1 every 40 s using a Raman spectrometer. The obtained spectra were regarded as a dataset matrix. A multivariate curve resolution with alternating least squares was applied to the dataset. A multivariate analysis based on the Raman spectrum revealed that raw materials, emulsions, and products were decomposed when the water-rich samples were emulsified. Additionally, we evaluated the kinetics of the synthesis. The effect of water content on emulsification was investigated using Raman spectroscopy. The molecular dynamics of the co-solvent model were also investigated. The phase-layer construction was consistent with the phase transition in the water-methanol imine samples.