Preparation and antibacterial activity of Schiff bases from O-carboxymethyl chitosan and para-substituted benzaldehydes

Seven Schiff bases were synthesized from O-carboxymethyl chitosan (CMC) and para-substituted benzaldehydes. The Schiff bases were characterized through Fourier Transform Infrared Spectroscopy, Carbon-13 Nuclear Magnetic Resonance (¹³C NMR), Distortionless Enhancement of Polarization Transfer (DEPT) 135 NMR, elemental analysis, and acid–base titration. Antibacterial activities of the Schiff bases against Escherichia coli (E. coli, ATCC 35218) and Staphylococcus aureus (S. aureus, ATCC 25923) were measured through the optical density method. Antibacterial activity of the Schiff bases differs from the substituent at the para position of benzaldehyde, and decreases as the sequence OCH₃ > CH₃ > H > F > Cl > Br > NO₂. The IC₅₀ of the Schiff base from 4-methoxylbenzylaldehyde against E. coli and S. aureus is 30 and 34 ppm, respectively, much lower than that of chitosan (53, 48 ppm) and CMC (58, 60 ppm).     

Effect of Schiff Bases Containing Pyridyl Group as Corrosion Inhibitors for Low Carbon Steel in 0.1 M HCl

The inhibiting effect of four newly synthesised Schiff bases containing pyridyl group was investigated on the corrosion of low carbon steel in 0.1 M hydrochloric acid solution under various conditions by potentiodynamic polarisation method and impedance measurements. The Schiff bases used were 2-((1Z)-1-aza-2-(2-pyridyl)vinyl)benzene-1-thiol, (1Z)-1-aza-1,2- di(2-pyridyl)ethene, [((1Z)-1-aza-2-(2-pyridyl)vinyl)amino]benzene-1-thione and 2-((1Z)-1-aza-2-(2-pyridyl)vinyl)benzothiazole. All the Schiff bases inhibit corrosion of low carbon steel and their inhibition efficiencies increase with decrease in temperature and increase in concentration. The difference in protection actions of the inhibitors can be attributed to the presence of substituents in the structures that increase or decrease the electron density on the azomethine (–C=N–) group. Polarisation curves indicate that the Schiff bases act as anodic inhibitors. AC impedance and potentiodynamic polarisation measurements reveal that the compounds are adsorbed on the steel surface and the adsorption obeys the Temkin isotherm. Activation parameters (E_a, ΔH*, ΔS*) for the corrosion of low carbon steel in 0.1 M HCl were calculated and showed that corrosion was much reduced in the presence of inhibitors.     

Some Schiff Base Surfactants as Steel-Corrosion Inhibitors

Two series of Schiff base amphiphiles were prepared by condensation of benzaldehyde or anisaldehyde with three different alkyl chain length fatty amines namely: dodecyl, hexadecyl and octadecyl amine. The chemical structures of the prepared Schiff bases were confirmed by using different techniques, (elemental analysis, FTIR and ¹H-NMR spectra). The data of structural analysis for these compounds were confirmed by the purity of the synthesized amphiphiles. The synthesized Schiff bases were evaluated as corrosion inhibitors for low carbon steel (mild steel) in various acidic media (HCl and H₂SO₄) using a weight loss technique. The corrosion inhibition measurements of these inhibitors showed high protection against corrosion process in the tested acidic media at different doses (50, 100, 150 and 200 ppm) as well as their having a good biocidal effect against sulphate reducing bacteria. The discussion correlated the efficient corrosion inhibition of these inhibitors to their chemical structures.     

Physicochemical Studies of 4-Substituted N-(2-Mercaptophenyl)-Salicylideneimines: Corrosion Inhibition of Mild Steel in an Acid Medium

A series of 4-substituted N-(2-mercaptophenyl)salicylideneimine Schiff bases were synthesized and investigated for corrosion inhibition of mild steel in hydrochloric acid medium. Inhibition through adsorption mechanism is proposed for these inhibitors, which is well supported by electrochemical impedance spectroscopy, the Langmuir adsorption isotherm and Scanning Electron Microscope morphologies of inhibited and uninhibited mild steel specimens. The negative ?G _ads indicates the spontaneous adsorption of the inhibitor on a mild steel surface. Among all the examined inhibitors, 5-bromo-N-(2-mercaptophenyl)salicylideneimine showed a higher inhibition efficiency. In order to reveal the usefulness of these Schiff bases as corrosion inhibitors under various circumstances, weight loss measurements were performed at various temperatures, acid concentrations and immersion times.     

Novel Furin Inhibitors with Potent Anti‐infectious Activity

New peptidomimetic furin inhibitors with unnatural amino acid residues in the P3 position were synthesized. The most potent compound 4‐guanidinomethyl‐phenylacteyl‐Arg‐Tle‐Arg‐4‐amidinobenzylamide (MI‐1148) inhibits furin with a K_i value of 5.5 pM . The derivatives also strongly inhibit PC1/3, whereas PC2 is less affected. Selected inhibitors were tested in cell culture for antibacterial and antiviral activity against infectious agents known to be dependent on furin activity. A significant protective effect against anthrax and diphtheria toxin was observed in the presence of the furin inhibitors. Furthermore, the spread of the highly pathogenic H5N1 and H7N1 avian influenza viruses and propagation of canine distemper virus was strongly inhibited. Inhibitor MI‐1148 was crystallized in complex with human furin. Its N‐terminal guanidinomethyl group in the para position of the P5 phenyl ring occupies the same position as that found previously for a structurally related inhibitor containing this substitution in the meta position, thereby maintaining all of the important P5 interactions. Our results confirm that the inhibition of furin is a promising strategy for a short‐term treatment of acute infectious diseases.     

Protection of mild steel corrosion with Schiff bases in 0.5 M H2SO4 solution

Three new Schiff bases, viz., N,N′-ethylen-bis (salicylidenimine) [S₁], N,N′-isopropylien-bis (salicylidenimine) [S₂], and N-acetylacetone imine, N′-(2-hydroxybenzophenone imine) ortho-phenylen [S₃] have been investigated as corrosion inhibitors for mild steel in 0.5 M H₂SO₄ using Tafel polarization and electrochemical impedance spectroscopy (EIS). The three Schiff bases function as good inhibitors reaching inhibition efficiencies of ∼97-98% at 300 ppm concentration. The fraction <theta> of the metal surface covered by the inhibitor is found to increase with inhibitor concentration. Of the three Schiff bases, the S2 shows better efficiency than the other two Schiff bases. The adsorption of the inhibitor follows Langmuir isortherm. Thermodynamic calculations indicate the adsorption to be physical in nature.     

Synthesis,extraction, and anti‐bacterial studies of some new bis‐1,2,4‐triazole derivatives part I

A series of new bis triazole Schiff base derivatives (4) were prepared in good yields by treatment of 4‐amino‐3,5‐diphenyl‐4H‐1,2,4‐triazole (3) with bisaldehydes (1). Schiff bases (4) were reduced with NaBH₄ to afford the corresponding bisaminotriazoles (5). All the new compounds were characterized by IR, ¹H NMR and ¹³C NMR spectral data. Their overall extraction (log K_ex) constants for 1 : 1 (M : L) complexes and CHCl₃/H₂O systems were determined at 25 ± 0.1°C to investigate the relationship between structure and selectivity toward various metal cations. The extraction equilibrium constants were estimated using CHCl₃/H₂O membrane transfer with inductively coupled plasma‐atomic emission spectroscopy spectroscopy. The stability sequence of the triazole derivatives in CHCl₃ for the metal cations was exhibited a characteristic preference order of extractability to metal ions [Fe(III) > Cu(II) > Pb(II) > Co(II) > Ni(II) > Mn(II) > Zn(II) > Mg(II) > Ca(II)]. The compounds were tested for anti‐microbial activity applying agar diffusion technique for 11 bacteria. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Preparation and antibacterial activity of C2-benzaldehyde-C6-aniline double Schiff base derivatives of chitosan

C₂-benzaldehyde-C₆-aniline double Schiff base derivatives of chitosan were synthesized with positioning protection method for the first time. The structures and properties of the new synthesized products were characterized by Fourier transform infrared spectroscopy, ¹³C nuclear magnetic resonance, scanning electron microscope image, X-ray diffraction, and elemental analysis. The elemental analysis results indicated that the degrees of substitution of the products were from 39.6% to 48.2%. The synthesized compounds exhibited an excellent solubility in organic solvents. The antibacterial activities of all of the derivatives were tested in the experiment, and the results showed that the prepared chitosan derivatives had significantly improved antibacterial activity of chitosan and C₂-benzaldehyde Schiff bases of chitosan toward Staphylococcus aureus (ATCC 25923) and Escherichia coli (ATCC 35218). Antibacterial activity of the Schiff bases against E. coli differs from the substituent at the same position of different anilines and increases as the sequence aniline?>?p-toluidine?>?o-toluidine, and the antibacterial activity of the Schiff bases against S. aureus increases as the sequence p-toluidine?>?aniline?>?o-toluidine. The I_C50 of the C₂-benzaldehyde-C₆-aniline double Schiff base derivatives of chitosan against E. coli and S. aureus is 0.0035 and 0.0031?mg?L^?1, respectively, much lower than that of chitosan (0.0064?mg?L^?1) and C₂-benzaldehyde Schiff bases of chitosan (0.0054?mg?L^?1). The cytotoxicity test showed that compared with chitosan and C₂-benzaldehyde Schiff bases of chitosan, the prepared chitosan derivatives had lower cytotoxicity against SCG-7901. This paper provided a new method for the synthesis of Schiff bases of chitosan, which was enlightening.     

Novel Monocyclam Derivatives as HIV Entry Inhibitors: Design,Synthesis, Anti‐HIV Evaluation,and Their Interaction with the CXCR4 Co‐receptor

The CXCR4 receptor has been shown to interact with the human immunodeficiency virus (HIV) envelope glycoprotein gp120, leading to fusion of viral and cell membranes. Therefore, ligands that can attach to this receptor represent an important class of therapeutic agents against HIV, thus inhibiting the first step in the cycle of viral infection: the virus–cell entry/fusion. Herein we describe the in silico design, synthesis, and biological evaluation of novel monocyclam derivatives as HIV entry inhibitors. In vitro activity testing of these compounds in cell cultures against HIV strains revealed EC₅₀ values in the low micromolar range without cytotoxicity at the concentrations tested. Docking and molecular dynamics simulations were performed to predict the binding interactions between CXCR4 and the novel monocyclam derivatives. A binding mode of these compounds is proposed which is consistent with the main existing site‐directed mutagenesis data on the CXCR4 co‐receptor. Moreover, molecular modeling comparisons were performed between these novel monocyclams, previously reported non‐cyclam compounds from which the monocyclams are derived, and the well‐known AMD3100 bicyclam CXCR4 inhibitors. Our results suggest that these three structurally diverse CXCR4 inhibitors bind to overlapping but not identical amino acid residues in the transmembrane regions of the receptor.     

Polycondensation of structurally divergent tetraamine monomers with dicarboxylic acids to synthesize polybenzimidazole copolymers for polymer electrolyte membranes

In our effort to promote 2,6‐bis(3,4‐diaminophenyl)‐4‐phenylpyridine (Py‐TAB) as an alternative tetraamine monomer to conventionally used 3,3′,4,4′‐tetraaminobiphenyl (TAB) for synthesizing readily processable pyridine bridged polybenzimidazoles (Py‐PBIs), two series of random copolymers (PBI‐co‐Py‐PBI) were synthesized by polymerizing Py‐TAB and TAB with isophthalic acid or terephthalic acid to produce meta (mPBI‐co‐mPy‐PBI) and para (pPBI‐co‐pPy‐PBI) connected copolymers, respectively. For the first time in the PBI literature, copolymers were synthesized by varying the relative compositions of tetraamines (TAB and Py‐TAB) in the polymerization feed with a single dicarboxylic acid (DCA) instead of the traditionally used method where two DCAs with variable compositions were polymerized with a single tetraamine. The solubility and hence the processability of the copolymers were improved significantly upon introduction of Py‐PBI in the copolymer. The detailed characterizations of both meta and para series copolymers compellingly established that thermal, chemical and mechanical stabilities can be easily modulated according to need by altering the relative compositions of PBI and Py‐PBI. The phosphoric acid (PA) loading of the copolymers increased gradually with increasing Py‐PBI content since the bulky pyridine moiety facilitated the absorption of PA. The presence of pyridine functionality and a larger PA loading caused a higher proton conductivity of PA doped copolymer membranes. © 2014 Society of Chemical Industry     

A New Class of 1‐Aryl‐5,6‐dihydropyrrolo[2,1‐a]isoquinoline Derivatives as Reversers of P‐Glycoprotein‐Mediated Multidrug Resistance in Tumor Cells

A number of aza‐heterocyclic compounds, which share the 5,6‐dihydropyrrolo[2,1‐a]isoquinoline (DHPIQ) scaffold with members of the lamellarin alkaloid family, were synthesized and evaluated for their ability to reverse in vitro multidrug resistance in cancer cells through inhibition of P‐glycoprotein (P‐gp) and/or multidrug‐resistance‐associated protein 1. Most of the investigated DHPIQ compounds proved to be selective P‐gp modulators, and the most potent modulator, 8,9‐diethoxy‐1‐(3,4‐diethoxyphenyl)‐3‐(furan‐2‐yl)‐5,6‐dihydropyrrolo[2,1‐a]isoquinoline‐2‐carbaldehyde, attained sub‐micromolar inhibitory potency (IC₅₀: 0.19 μm ). Schiff bases prepared by the condensation of some 1‐aryl‐DHPIQ aldehydes with p‐aminophenol also proved to be of some interest, and one of them, 4‐((1‐(4‐fluorophenyl)‐5,6‐dihydro‐8,9‐dimethoxypyrrolo[2,1‐a]isoquinolin‐2‐yl)methyleneamino)phenol, had an IC₅₀ value of 1.01 μm . In drug combination assays in multidrug‐resistant cells, some DHPIQ compounds, at nontoxic concentrations, significantly increased the cytotoxicity of doxorubicin in a concentration‐dependent manner. Studies of structure–activity relationships and investigation of the chemical stability of Schiff bases provided physicochemical information useful for molecular optimization of lamellarin‐like cytotoxic drugs active toward chemoresistant tumors as well as nontoxic reversers of P‐gp‐mediated multidrug resistance in tumor cells.     

Monoamine Oxidase (MAO) Inhibitory Activity: 3‐Phenylcoumarins versus 4‐Hydroxy‐3‐phenylcoumarins

Monoamine oxidase (MAO) is a useful target in the treatment of neurodegenerative diseases and depressive disorders. Both isoforms, MAO‐A and MAO‐B, are known to play critical roles in disease progression, and as such, the identification of novel, potent and selective inhibitors is an important research goal. Here, two series of 3‐phenylcoumarin derivatives were synthesized and evaluated against MAO‐A and MAO‐B. Most of the compounds tested acted preferentially on MAO‐B, with IC₅₀ values in the micromolar to nanomolar range. Only 6‐chloro‐4‐hydroxy‐3‐(2’‐hydroxyphenyl)coumarin exhibited activity against the MAO‐A isoform, while still retaining good selectivity for MAO‐B. 6‐Chloro‐3‐phenylcoumarins unsubstituted at the 4 position were found to be more active as MAO‐B inhibitors than the corresponding 4‐hydroxylated coumarins. For 4‐unsubstituted coumarins, meta and para positions on the 3‐phenyl ring seem to be the most favorable for substitution. Molecular docking simulations were used to explain the observed hMAO‐B structure–activity relationships for this type of compound. 6‐Chloro‐3‐(3’‐methoxyphenyl)coumarin was the most active compound identified (IC₅₀=0.001 μM ) and is several times more potent and selective than the reference compound, R‐(?)‐deprenyl hydrochloride. This compound represents a novel tool for the further investigation of the therapeutic potential of MAO‐B inhibitors.     

Highly potent and selective 4,4'‐biphenyl‐4‐acylate‐4'‐N‐n‐butylcarbamate inhibitors of Pseudomonas species lipase

4,4'‐Biphenyl‐4‐acylate‐4'‐N‐n‐butylcarbamates ( 1–8 ) are synthesized and characterized as highly potent and selective pseudo‐substrate inhibitors of Pseudomonas species lipase. Thus, the n‐butylcarbamate moieties of the inhibitors bind to the first acyl chain binding site (ACS) of the enzyme. Therefore, the ester moieties of the inhibitors may bind to the second ACS of the enzyme, due to the linear 4,4'‐biphenyl moiety of the inhibitors. –logK_i, logk₂, and logk_i values of carbamates 1–8 are multiply linearly correlated with the Taft steric constant (E_S) and the Hansch hydrophobicity constant (π), but not with the Taft substituent constant (σ*). For –logK_i, logk₂, and logk_i correlations, values of δ are 0.8, 0.34, and 1.0, respectively, and values of ψ are 1.0, 0.4, and 1.3, respectively. Positive δ and ψ values for these correlations indicate that the second ACS of the enzyme prefers to bind to small and hydrophobic ester groups of the inhibitors. Among carbamates 1–8 , carbamate 3 , with a K_i value of 2.5 nM, is the most potent inhibitor.     

Influence of the steric effects of the Schiff bases and the hydrogen bonds on the bridging modes of the azide groups: Syntheses and crystal structures of three azide-bridged Schiff base zinc(II) complexes

Three polymeric zinc(II) complexes, derived from the end-on azide (μ_1,1-N₃) and end-to-end azide (μ_1,3-N₃) bridges and similar tridentate Schiff base ligands, have been synthesized and structurally characterized. The zinc(II) atom in each complex is in a midway between trigonal–bipyramidal and square–pyramidal coordination. The slight difference of the steric effects of the Schiff bases and the hydrogen bonds can influence the bridging modes of the azide groups.     

Aryloxyethyl Thiocyanates Are Potent Growth Inhibitors of Trypanosoma cruzi and Toxoplasma gondii

As a part of our project aimed at searching for new safe chemotherapeutic agents against parasitic diseases, several compounds structurally related to the antiparasitic agent WC‐9 (4‐phenoxyphenoxyethyl thiocyanate), which were modified at the terminal phenyl ring, were designed, synthesized, and evaluated as growth inhibitors against Trypanosoma cruzi, the etiological agent of Chagas disease, and Toxoplasma gondii, the parasite responsible of toxoplasmosis. Most of the synthetic analogues exhibited similar antiparasitic activity and were slightly more potent than our lead WC‐9. For example, two trifluoromethylated derivatives exhibited ED₅₀ values of 10.0 and 9.2 μM against intracellular T. cruzi, whereas they showed potent action against tachyzoites of T. gondii (ED₅₀ values of 1.6 and 1.9 μM against T. gondii). In addition, analogues of WC‐9 in which the terminal aryl group is in the meta position with respect to the alkyl chain bearing the thiocyanate group showed potent inhibitory action against both T. cruzi and T. gondii at the very low micromolar range, which suggests that a para‐phenyl substitution pattern is not necessary for biological activity.     

A water-soluble,neutral {aqua-VV}2 complex with a biomimetic ONO ligand set

The water-soluble complex [{VO(van-L-ser)H₂O}₂μ-O], where van-L-ser is the Schiff base formed from o-vanillin and L-serine, has been prepared and structurally characterised. Characteristics, including the hydrogen bonding network, are addressed in the context of biologically relevant vanadium compounds.     

Comparative study of the influence of active groups of chitosan derivatives on antifungal activity

In this study, series of chitosan derivatives containing active groups were synthesized and evaluated for their antifungal activity against three crop‐threatening fungi, Fusarium oxysporum. f. sp. Vasinfectum, Alternaria solani, and Valsa mali. Schiff bases of carboxymethyl chitosan (As: 2‐(2‐hydroxy‐5‐nitrobenzylideneamino)‐6‐carboxymethyl chitosan; Bs: 2‐(2‐hydroxyl‐5‐chlorobenzaldimino)‐6‐carboxymethyl chitosan), N‐substituted carboxymethyl chitosan (An: 2‐(2‐hydroxyl‐5‐nitrobenzylamino)‐6‐carboxymethyl chitosan; Bn: 2‐(2‐hydroxyl‐5‐chlorobenzylamino)‐6‐carboxymethyl chitosan) and 2‐urea‐carboxymethyl chitosan (Au: 2‐(2‐nitrophenylurea)‐6‐carboxymethyl chitosan; Bu: 2‐(2‐chlorophenylurea)‐6‐carboxymethyl chitosan) were synthesized, and their antifungal activity was comparatively studied by hypha measurement in vitro, respectively. Results obtained from this study revealed that the active groups combined with Schiff bases functional groups (C?N) could strengthen the antifungal activity most effectively among the compounds studied in this work. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Ruthenium‐Catalyzed Remote Electronic Activation of Aromatic C?F Bonds

The tandem isomerization and nucleophilic aromatic substitution of allylic fluoro‐substituted benzylic alcohols is described for the first time. In the presence of the ruthenium complex Ru(PPh₃)₃(CO)(H)₂, 1‐(4‐fluorophenyl)prop‐2‐en‐1‐ol is converted into the corresponding para‐amino ketone or para‐phenolic substituted ketone.     

1,2,4-Triazole-3-Thione Analogues with a 2-Ethylbenzoic Acid at Position 4 as VIM-type Metallo-β-Lactamase Inhibitors

Metallo-β-lactamases (MBLs) are increasingly involved as a major mechanism of resistance to carbapenems in relevant opportunistic Gram-negative pathogens. Unfortunately, clinically efficient MBL inhibitors still represent an unmet medical need. We previously reported several series of compounds based on the 1,2,4-triazole-3-thione scaffold. In particular, Schiff bases formed between diversely 5-substituted-4-amino compounds and 2-carboxybenzaldehyde were broad-spectrum inhibitors of VIM-type, NDM-1 and IMP-1 MBLs. Unfortunately, these compounds were unable to restore antibiotic susceptibility of MBL-producing bacteria, probably because of poor penetration and/or susceptibility to hydrolysis. To improve their microbiological activity, we synthesized and characterized compounds where the hydrazone-like bond of the Schiff base analogues was replaced by a stable ethyl link. This small change resulted in a narrower inhibition spectrum, as all compounds were poorly or not inhibiting NDM-1 and IMP-1, but showed a significantly better activity on VIM-type enzymes, with K_i values in the μM to sub-μM range. The resolution of the crystallographic structure of VIM-2 in complex with one of the best inhibitors yielded valuable information about their binding mode. Interestingly, several compounds were shown to restore the β-lactam susceptibility of VIM-type-producing E. coli laboratory strains and also of K. pneumoniae clinical isolates. In addition, selected compounds were found to be devoid of toxicity toward human cancer cells at high concentration, thus showing promising safety.     

Synthesis of poly(1‐hexene)s end‐functionalized with phenols

Electrophilic alkylations of phenol/2,6‐dimethylphenol were performed with vinylidene‐terminated poly(1‐hexene)s using BF₃·OEt₂ catalyst. Vinylidene‐terminated poly(1‐hexene)s with M_n varying from 400 to 10000 were prepared by bulk polymerization of 1‐hexene at 50 to ?20 °C using Cp₂ZrCl₂/MAO catalysts. The phenol/2,6‐dimethylphenol‐terminated poly(1‐hexene)s was characterized by NMR (¹H, ¹³C), UV, IR and vapor phase osmometer (VPO). The isomer distribution (ortho, para and ortho/para) was determined by ¹³P NMR using a phosphitylating reagent, namely 2‐chloro‐1,3,2‐dioxaphospholane. The number‐average degree of functionality (F_n) >0.9 with >95% para selectivity could be achieved using low‐molecular‐weight oligomers of poly(1‐hexene)s. Copyright © 2005 Society of Chemical Industry