An inhibitor of nonhomologous end-joining abrogates double-strand break repair and impedes cancer progression.

DNA Ligase IV is responsible for sealing of double-strand breaks (DSBs) during nonhomologous end-joining (NHEJ). Inhibiting Ligase IV could result in amassing of DSBs, thereby serving as a strategy toward treatment of cancer. Here, we identify a molecule, SCR7 that inhibits joining of DSBs in cell-free repair system. SCR7 blocks Ligase IV-mediated joining by interfering with its DNA binding but not that of T4 DNA Ligase or Ligase I. SCR7 inhibits NHEJ in a Ligase IV-dependent manner within cells, and activates the intrinsic apoptotic pathway. More importantly, SCR7 impedes tumor progression in mouse models and when coadministered with DSB-inducing therapeutic modalities enhances their sensitivity significantly. This inhibitor to target NHEJ offers a strategy toward the treatment of cancer and improvement of existing regimens.

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, Antimicrobial and In Silico Studies of Isatin Schiff Base Linked 1,2,3-Triazole Hybrids.

A new series of isatin-Schiff base linked 1,2,3-triazole hybrids has been synthesized using CuAAC approach from (E)-3-(phenylimino)-1-(prop-2-yn-1-yl)indolin-2-one derivatives in high yield (73-91 %). These synthesized derivatives were characterized using FT-IR, 1H NMR, 13C NMR, 2D-NMR and HRMS spectral techniques. The in vitro antimicrobial activity assay demonstrated that most of the tested hybrids exhibited promising activity. Compound 5 j displayed significant antibacterial efficacy against P. aeruginosa and B. subtilis with MIC value of 0.0062 µmol/mL. While, 5 j also showed better antifungal potency against A. niger with MIC value of 0.0123 µmol/mL. The docking studies of most promising compounds were performed with the well-known antibacterial and antifungal targets i. e. 1KZ1, 5TZ1. Molecular modelling investigations demonstrated that hybrids 5 h and 5 l exhibited good interactions with 1KZN and 5TZ1, with binding energies of -9.6 and -11.0 kcal/mol, respectively. Further, molecular dynamics studies of the compounds showing promising binding interactions were also carried out to study the stability of complexes of these hybrids with both the targets.

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.

Efficient, rapid, and high-yield synthesis of aryl Schiff base derivatives and their in vitro and in silico inhibition studies of hCA I, hCA II, AChE, and BuChE.

This study reports a rapid and efficient synthesis of four novel aryl Schiff base derivatives. Biological activity and molecular modeling studies were conducted to evaluate the inhibitory effects of these compounds on human carbonic anhydrases (hCA) and cholinesterases. The results indicate that the triazole-ring-containing compounds have strong inhibitory effects on hCA I, hCA II, acetylcholinesterase (AChE), and butyrylcholinesterase (BuChE) targets. Besides comparing the Schiff bases synthesized in our study to reference molecules, we conducted in silico investigations to examine how these compounds interact with their targets. Our studies revealed that these compounds can occupy binding sites and establish interactions with crucial residues, thus inhibiting the functions of the targets. These findings have significant implications as they can be utilized to develop more potent compounds for treating the diseases that these target proteins play crucial roles in or to obtain drug precursors with enhanced efficacy.

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.

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.

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.

Phototriggered cytotoxic properties of tricarbonyl manganese(I) complexes bearing α-diimine ligands towards HepG2.

Reaction between bromo tricarbonyl manganese(I) and N,N'-bis(phenyl)-1,4-diaza-1,3-butadiene ligands, bearing different electron-donating and electron-withdrawing groups R = OCH3, Cl, and NO2 in the ortho- and para-positions on the phenyl substituent, afforded [MnBr(CO)3(N-N)] complexes. The influence of the character and position of the substituent on the dark stability and carbon monoxide releasing kinetics was systematically investigated and correlated with the data of the time-dependent density functional theory calculations. The combined UV/Vis and IR data clearly revealed that the aerated solutions of [MnBr(CO)3(N-N)] in either coordinating or noncoordinating solvents are dark stable and the fluctuations observed during the incubation period especially in the case of the nitro derivatives may be attributed to the exchange of the axial bromo ligand with the coordinating solvent molecules. The free ligands and nitro complexes were non-cytotoxic to HepG2 cells under both the dark and illumination conditions. In the dark, Mn(I) compounds, incorporating o-OCH3 and o-Cl, exhibited excellent cytotoxicity with IC50 values of 18.1 and 11.8 µM, while their para-substituted analogues were inactive in the dark and active upon the irradiation at 365 nm with IC50 values of 5.7 and 6.7 µM, respectively.

In vitro antifungal activities, molecular docking, and DFT studies of 4-amine-3-hydrazino-5-mercapto-1,2,4-triazole derivatives.

Six disubstituted Schiff base compounds were synthesized (A1-A6) and characterized using infrared spectroscopy (IR), elemental analyses (EA), 1H NMR, 13C NMR and HRMS spectroscopic techniques. Crystal structure of A1 has been determined by single crystal X-ray diffraction. The antifungal activities against three fungi were assessed, and the results showed that compounds of A1 and A2 have good activity for Wheat gibberellic with EC50 value of 15.89 and 16.99 mg/L, respectively. Compounds of A3, A4 and A6 have good bioactivity against Maize rough bacteria (the value of EC50 is 8.23, 7.56 and 7.92 mg/L, respectively). According to the result of molecular docking, compounds of A1 and A2 have the smallest docking energy (-8.33, -9.00 kcal/mol). Besides, for A1 and A2, the analysis of highest occupied molecular orbital (HOMO), the lowest unoccupied molecular orbital (LUMO) analysis and molecular electrostatic potential map were to further elaborate the reason for the good activity with density functional theory (DFT)-B3LYP/6-31G.

Cytotoxic oxidovanadium(IV) complexes of tridentate halogen-substituted Schiff bases: First dinuclear V(IV) complexes with O → VIV = O → VIV = O core.

The reaction of potentially N,N,O-tridentate Schiff base ligands, Cl-LH, Br-LH, BrCl-LH and H-LH, with [VIVO(acac)2] in 2:1 ratio in methanol gave the corresponding mononuclear and dinuclear oxidovanadium(IV) complexes, VO(Cl-L)2 (1), VO(Br-L)2 (2), [(BrCl-L)2(H2O)V(µ-O)VO(BrCl-L)2] (3) and [(H-L)2(H2O)V(µ -O)VO(H-L)2] (4), in good yields. The ligands and complexes were fully characterized by elemental analysis and FT-IR spectroscopy. The ligands were also characterized by 1H NMR spectroscopy. The oxidation state of V(IV)O with d1 configuration in all synthesized complexes was confirmed by EPR. Moreover, the structures of 2 and 3 were determined by X-ray diffraction (XRD) analysis which revealed them as mono- and dinuclear vanadium(IV) complexes, respectively, with the ligands coordinated as bidentate chelates. The structure of 3 represents the first example of dinuclear V(IV) complex with O â†’ VIV = O â†’ VIV = O core (Cambridge Structural Database (CSD)​, version 5.42, update of May 2021). The cytotoxicity of ligands and complexes was evaluated towards ovarian (A2780), breast (MCF7) and prostate (PC3) cancer cells at 48 h. While ligands showed modest IC50 values (>42 µM), all complexes turned out to be effective in the range 3.9-17.2 µM. In particular, A2780 and MCF7 cell lines were the most sensitive to the newly synthesized V(IV)O complexes.

Copper(II) N,N,O-Chelating Complexes as Potential Anticancer Agents.

Three novel dinuclear Cu(II) complexes based on a N,N,O-chelating salphen-like ligand scaffold and bearing varying aromatic substituents (-H, -Cl, and -Br) have been synthesized and characterized. The experimental and computational data obtained suggest that all three complexes exist in the dimeric form in the solid state and adopt the same conformation. The mass spectrometry and electron paramagnetic resonance results indicate that the dimeric structure coexists with the monomeric form in solution upon solvent (dimethyl sulfoxide and water) coordination. The three synthesized Cu(II) complexes exhibit high potentiality as ROS generators, with the Cu(II)/Cu(I) redox potential inside the biological redox window, and thus being able to biologically undergo Cu(II)/Cu(I) redox cycling. The formation of ROS is one of the most promising reported cell death mechanisms for metal complexes to offer an inherent selectivity to cancer cells. In vitro cytotoxic studies in two different cancer cell lines (HeLa and MCF7) and in a normal fibroblast cell line show promising selective cytotoxicity for cancer cells (IC50 about 25 µM in HeLa cells, which is in the range of cisplatin and improved with respect to carboplatin), hence placing this N,N,O-chelating salphen-like metallic core as a promising scaffold to be explored in the design of future tailor-made Cu(II) cytotoxic compounds.

Disruption of the Microtubule Network and Inhibition of VEGFR2 Phosphorylation by Cytotoxic N,O-Coordinated Pt(II) and Ru(II) Complexes of Trimethoxy Aniline-Based Schiff Bases.

Platinum-based complexes are one of the most successful chemotherapeutic agents having a significant ground in cancer chemotherapy despite their side effects. During the past few decades, Ru(II) complexes have been emerging as efficient alternatives owing to their promising activities against platinum-resistant cancer. The pathway of action, lipophilicity, and cytotoxicity of a Pt or Ru complex may be tuned by varying the attached ligands, the coordination mode, and the leaving group. In this work, we report a family of Pt(II) and Ru(II) complexes (1-5) of three N,O and N,N donor-based trimethoxyanilines containing Schiff bases with the general formula [PtII(L)(DMSO)Cl], [RuII(L)(p-cymene)Cl], [RuII(L)(p-cymene)Cl]+, and [PtII(L)Cl2]. All of the complexes are characterized by different analytical techniques. 1H NMR and electrospray ionization mass spectrometry (ESI-MS) data suggest that the N,O-coordinated Pt(II) complexes undergo slower aquation compared to the Ru(II) analogues. The change of the coordination mode to N,N causes the Ru complexes to be more inert to aquation. The N,O-coordinating complexes show superiority over N,N-coordinating complexes by displaying excellent in vitro antiproliferative activity against different aggressive cancer cells, viz., triple-negative human metastatic breast adenocarcinoma MDA-MB-231, human pancreatic carcinoma MIA PaCa-2, and hepatocellular carcinoma Hep G2. In vitro cytotoxicity studies suggest that Pt(II) complexes are more effective than their corresponding Ru(II) analogues, and the most cytotoxic complex 3 is 10-15 times more toxic than the clinical drugs cisplatin and oxaliplatin against MDA-MB-231 cells. Cellular studies show that all of the N,O-coordinated complexes (1-3) initiate disruption of the microtubule network in MDA-MB-231 cells in a dose-dependent manner within 6 h of incubation and finally lead to the arrest of the cell cycle in the G2/M phase and render apoptotic cell death. The disruption of the microtubule network affects the agility of the cytoskeleton rendering inhibition of tyrosine phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2), a key step in angiogenesis. Complexes 1 and 2 inhibit VEGFR2 phosphorylation in a dose-dependent fashion. Among the Pt(II) and Ru(II) complexes, the former displays higher cytotoxicity, a stronger effect on the cytoskeleton, better VEGFR2 inhibition, and strong interaction with the model nucleobase 9-ethylguanine (9-EtG).

Quantum mechanical study on the activation mechanism of human carbonic anhydrase VII cluster model with bis-histamine schiff bases and bis-spinaceamine derivatives.

The activation mechanism of human carbonic anhydrase (hCA) isoform VII, hCA VII, with histamine, histamine bis-Schiff bases and bis-spinaceamine derivatives has been investigated using quantum mechanical calculations. The DFT-D3 method has been employed to calculate in detail the electronic structure and electronic energy of different compounds and complexes throughout the reaction pathway. The model system of hCA VII included the core catalytic center, the Zn2+ ion, its three histidine ligands and a hydroxide ion or water molecule coordinated to it. Furthermore, Thr199, Glu106 and the deep water molecule were considered in the model. Five activators of this enzyme, including histamine as standard, in complex with the cluster model of hCA VII were investigated. Thermodynamic functions for the overall reaction and for the complexation between activators and hCA VII were evaluated. Our results demonstrate that the protonatable moiety of these activators participates in proton transfer reactions from the zinc-bound water molecule to the reaction medium, promoting the formation of the catalytically active zinc hydroxide species of the enzyme. The QM analysis revealed that the electrostatic interactions between activators and hCA VII are the driving force of the enzyme-activator complex formation.

Novel Schiff base-bridged multi-component sulfonamide imidazole hybrids as potentially highly selective DNA-targeting membrane active repressors against methicillin-resistant Staphylococcus aureus.

A new type of Schiff base-bridged multi-component sulfonamide imidazole hybrids with antimicrobial potential was developed. Some target compounds showed significant antibacterial potency. Observably, butylene hybrids 4h exhibited remarkable inhibitory efficacy against clinical MRSA (MIC = 1 µg/mL), but had no significant toxic effect on normal mammalian cells (RAW 264.7). The highly active molecule 4h was revealed by molecular modeling study that it could insert into the base-pairs of DNA hexamer duplex and bind with the ASN-62 residue of human carbonic anhydrase isozyme II through hydrogen bonding. Furthermore, further preliminary antibacterial mechanism experiments confirmed that compound 4h could effectively interfere with MRSA membrane and insert into bacterial DNA isolated from clinical MRSA strains through non-covalent bonding to produce a supramolecular complex, thus exerting its strong antibacterial efficacy by impeding DNA replication. These findings strongly implied that the highly active hybrid 4h could be used as a potential DNA-targeting template for the development of valuable antimicrobial agent.

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.

Synthesis, design, and assessment of novel morpholine-derived Mannich bases as multifunctional agents for the potential enzyme inhibitory properties including docking study.

The synthesized Schiff Bases were reacted with formaldehyde and secondary amine such as 2,6-dimethylmorpholine to afford N-Mannich bases through the Mannich reaction. 3-Substitued-4-(4-hydroxybenzylidenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones (4) were treated with 2,6-dimethylmorpholine in the presence of formaldehyde to synthesize eight new 1-(2,6-dimethylmorpholino-4-yl-methyl)-3-substitued-4-(4-hydroxybenzylidenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones (4a-h). The structures of the synthesized eight new compounds were characterized using IR, 1H NMR, 13C NMR, and HR-MS spectroscopic methods. Synthesized compounds inhibitory activity determined against the acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and glutathione S-transferase (GST) enzymes with Ki values in the range 25.23-42.19 µM for AChE, 19.37-34.22 µM for BChE, and 21.84-41.14 µM for GST, respectively. Binding scores of most active inhibitors against AChE, BChE, and GST enzymes were detected as -10.294 kcal/mol, -9.562 kcal/mol, and -7.112 kcal/mol, respectively. The hydroxybenzylidene moiety of the most active inhibitors caused to inhibition of the enzymes through hydrophobic interaction and hydrogen bond.

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.

Cytotoxicity and Antibacterial Evaluation of O-Alkylated/Acylated Quinazolin-4-one Schiff Bases.

A series of quinazolin-4-one Schiff bases were synthesized and tested in vitro for their cytotoxicity against two cancerous cell lines (MCF-7, Caco-2) and a human embryonic cell line (HEK-293) including their antibacterial evaluation against two Gram-positive and four Gram-negative bacterial strains. Most of the quinazoline-Schiff bases exhibited potent cytotoxicity against Caco-2. 3-[(Z)-({4-[(But-2-yn-1-yl)oxy]phenyl}methylidene)amino]-2-methylquinazolin-4(3H)-one (6f) with the O-butyne functional group displayed three-fold higher cytotoxic activity (IC50 =376.8 µM) as compared to 5-fluorouracil (5-FU; IC50 =1086.1 µM). However, all compounds were found to be toxic to HEK-293, except for 3-[(Z)-({4-[(2,4-difluorophenyl)methoxy]phenyl}methylidene)amino]-2-methylquinazolin-4(3H)-one (6h) that showed ∼three-fold lower toxicity and higher selectivity index than 5-FU. Structure-activity relationship (SAR) analysis revealed that O-alkylation generally increased the anticancer activity and selectivity of quinazoline-4-one Schiff bases toward Caco-2 cells. The fluorinated Schiff-base generally exhibited even more significant cytotoxic activity compared to their chlorine analogs. Surprisingly, none of the quinazoline-4-one Schiff bases displayed encouraging antibacterial activity against the bacterial strains investigated. Most of the compounds were predicted to show compliance with the Lipinski parameters and ADMET profiles, indicating their drug-like properties.

In situ controllable synthesis of Schiff base networks porous polymer coatings for open-tubular capillary electrochromatography.

A uniform Schiff base network (SNW) film was synthesized in situ in a controllable way through continuous flow of reactants inside the capillary. The properties and application of the as-prepared capillary was investigated in capillary electrochromatography. The effects of reaction monomer concentration and reaction time on coating thickness were studied by SEM. The results show that the reaction condition has a significant influence on the morphology and thickness of the SNW films. The thickness of the film can be controlled by changing the concentration of reaction solution and reaction time. Capillaries coated under different conditions were employed to separate four nucleotides by capillary electrochromatography, which demonstrated significant variation of migration time, peak order, and separation efficiency. Analytes containing nitrogen heterocycle structures, such as nucleotides, methylimidazole isomers, and ß-lactam antibiotics, were successfully separated with the prepared open-tubular columns. Under the selected separation conditions, theoretical plate number of four nucleotides is in a range 45,237-104,505 plates·m-1, and the resolutions are 1.98-8.07. A resolution of 1.75 is obtained for methylimidazole isomers. The nucleotides in a real sample, chicken essence seasoning, were determined using the prepared capillary column with satisfactory recoveries in the range 95 to 105%.