Synthesis and antitubercular activity of novel Schiff bases derived from d-mannitol

Six Schiff base derivatives of d-mannitol, 1,6-dideoxy-1,6-bis-{[(E)-arylmethylidene]amino}-d-mannitol (6: aryl = XC₆H₄: X = o-, m- and p- Cl or NO₂), have been synthesized and evaluated for their in vitro antibacterial activity against Mycobacterium tuberculosis H₃₇Rv using the Alamar Blue susceptibility test and the activity expressed as the minimum inhibitory concentration (MIC) in μg/mL. All three nitro derivatives exhibit significant activities: activities of (6d: X = o-NO₂), (6e: X = m-NO₂) and (6f: X = p-NO₂) are 12.5, 25.0 and 25.0 μg/mL, respectively. When compared with first line drugs, such as ethambutol, they can be considered as a good starting point to develop new lead compounds for the treatment of multidrug-resistant tuberculosis. Characterization of the new compounds 6 is generally achieved spectroscopically. The structure of compound 3 has been confirmed by X-ray crystallography.     

Unexpected isomeric equilibrium in pyridoxamine Schiff bases

Pyridoxamine is a vitamin B₆ derivative involved in biological reactions such as transamination, and can also act as inhibitor in protein glycation. In both cases, it has been reported that Schiff base formation between pyridoxamine and carbonyl compounds is the main step. Nevertheless, few studies on the Schiff base formation have been reported to date. In this work, we conduct a comparative study of the reaction of pyridoxamine and 4-picolylamin (a pyridoxamine analog) with various carbonyl compounds including propanal, formaldehyde and pyruvic acid. Based on the results, 4-picolylamin forms a Schiff base as end-product of its reactions with propanal and pyruvic acid, but a carbinolamine with formaldehyde. On the other hand, pyridoxamine forms a Schiff base with the three reagents, but the end-product is in equilibrium with its hemiaminal form, which results from the attack of the phenolate ion of the pyridine ring on the imine carbon. This isomeric equilibrium should be considered in studying reactions involving amine derivatives of vitamin B₆.     

Sulfenylation of chiral Schiff bases

Summary The purpose of this study was to examine the conditions of sulfenylation reactions of chiral-amino esters Schiff bases to protect the chirality in the-position.     

Antibacterial and antifungal metal based triazole Schiff bases

A new series of four biologically active triazole derived Schiff base ligands (L¹–L⁴) and their cobalt(II), nickel(II), copper(II) and zinc(II) complexes (1–16) have been synthesized and characterized. The ligands were prepared by the condensation reaction of 3-amino-5-methylthio-1H-1,2,4-triazole with chloro-, bromo- and nitro-substituted 2-hydroxybenzaldehyde in an equimolar ratio. The antibacterial and antifungal bioactivity data showed the metal(II) complexes to be more potent antibacterial and antifungal than the parent Schiff bases against one or more bacterial and fungal species.     

Influence of some reactional parameters on the substitution degree of biopolymeric Schiff bases prepared from chitosan and salicylaldehyde

Some reactional parameters as mol ratio (salicylaldehyde:free amino groups), reaction time and temperature were investigated in order to improve the substitution degree (DS) in the preparation of biopolymeric Schiff bases from chitosan. In this case, the reaction of chitosan and salicylaldehyde was used as a probe system in order to produce the Schiff base. The use of 50% (mol/mol) salicylaldehyde excess, reaction time of 18 h and temperature of 55 °C permitted to obtain a DS of 60% without evidences of hydrolysis of the biopolymeric matrix or changes in its acetylation degree.     

Substituted benzenediol Schiff bases as promising new anti-glycation agents

A feature of diabetes is that the rate of protein glycation and the formation of advanced glycation endproducts (AGEs) increases spontaneously due to the abnormally elevated levels of sugar in the blood. The glycation of proteins is associated with a large number of late diabetic complications (retinopathy, neuropathy, atherosclerosis, end stage renal diseases, rheumatoid arthritis and neurodegenerative diseases). The increase in diabetic complications is a major cause of morbidity and mortality, which has increased significantly in the last two decades. Therefore, there is a considerable recent interest in the identification of lead molecules, which can inhibit the glycation process or slow it down considerably. A new class of anti-glycation agents has been identified, based on the spectrofluorimetric analysis of fluorescent advanced glycation endproducts (AGEs), benzenediol Schiff bases, and their structure-activity relationships have been studied. Some of these compounds have shown a promising anti-glycation potential in vitro.     

Enzymatic assay of d-glucuronate using uronate dehydrogenase

d-Glucuronate is a key metabolite in the process of detoxification of xenobiotics and in a recently constructed synthetic pathway to produce d-glucaric acid, a “top value-added chemical” from biomass. A simple and specific assay of d-glucuronate would be useful for studying these processes, but existing assays are either time-consuming or nonspecific. Using uronate dehydrogenase cloned from Agrobacterium tumefaciens, we developed an assay for d-glucuronate with a detection limit of 5 μM. This method was shown to be more suitable for a system with many interfering compounds than previous methods and was also applied to assays for myo-inositol oxygenase activity.     

Functionalisation of silica gel with cyclic and acyclic Schiff bases and related d- and/or f-metal complexes

Two different synthetic pathways were devised in order to graft on silica gel organic moieties, containing macroacyclic or macrocyclic compartimental ligands, formed of an inner N₃O₂ or N₂O₂ Schiff base site, able to coordinate d metal ions, and one adjacent O₂O₂ or O₂O₄ crown ether-like chamber suitable for hosting f ions, in the terminal part. These materials can bind d metal ions into the amine-imine moiety. Their subsequent reaction with varying amounts of gadolinium(III) invariantly gives a system in which two grafted copper complexes coordinate only one gadolinium(III) ion with their oxygen-containing chambers, giving rise to a trinuclear Cu₂Gd entity.According to a third strategy, some mono- and heterobi-metallic macrocyclic complexes were transferred from a water/methanol solution into functionalised silica platforms by coordinating their metal ions to the donor group of one silica-anchored organic residual. UV-Vis spectra of solutions containing these metal complexes gave a clear indication of the selective coordinating ability of the donor group towards 3d or 4f metal ions.     

Synthesis and aggregation phenomena of multifunctional Schiff bases and Ni(II) complexes: an X-ray investigation

Multifunctional Schiff base ligands Lⁿ, namely the tetradentate N,N^′-bis[2-hydroxy-5-(azopyridine)benzylidene]propylendiamine and the bidentate N-dodecyl-5-(azopyridine)salicylaldimine, both containing a flexible azo spacer, a metallation site and a terminal pyridine group, were synthetised and fully characterised. Mesogenic structures, analysed by polarised optical microscopy, DSC and powder X-ray diffraction, were obtained from self-assembly of the mono or bifunctional hydrogen-bond acceptors Lⁿ with carboxylic acid donors. Ni(II) mono and bis-chelate, four- and six-coordinated, Lⁿ derivatives were synthetised. The octahedral structure of the [Ni(py)₂(L²)₂] complex was confirmed by single crystal X-ray analysis. H-bonded self-assembly of Ni(II) complexes and carboxylic acids results in the formation of supramolecular networks whose structure and thermal stability were studied by DSC and powder X-ray diffraction analysis at variable temperatures.     

An insight into synthetic Schiff bases revealing antiproliferative activities in vitro

Schiff bases or azomethines are among the most important groups of biomolecules. These compounds have been found to reveal both remarkable biological activities and a variety of valuable practical applications. An interest in the exploration of novel series of synthetic Schiff bases has undoubtedly been growing due to their proven utility as attractive lead structures for the design of novel cytotoxic and cytostatic agents with a mechanism of action that sometimes differs from that of clinically authorized anticancer agents. Therefore, in the present paper we have focussed our attention on the collected synthetic simple Schiff bases of aldimine- and ketimine-types revealing anticancer activities in vitro, that have been described in the scientific literature during the last decade, and on structural variations whose affect the antiproliferative activity in sets of the designed molecules.     

Antifungal properties of Schiff bases of chitosan, N-substituted chitosan and quaternized chitosan

Schiff bases of chitosan, N-substituted chitosan, and quaternized chitosan were synthesized and their antifungal properties were analyzed against Botrytis cinerea Pers. (B. cinerea pers.) and Colletotrichum lagenarium (Pass) Ell.et halst (C. lagenarium (Pass) Ell.et halst) based on the method of D. Jasso de Rodríguez and co-workers. The results showed that quaternized chitosan had better inhibitory properties than chitosan, Schiff bases of chitosan, and N-substituted chitosan.     

Distribution of radiolabeled l-glutamate and d-aspartate from blood into peripheral tissues in naive rats: Significance for brain neuroprotection

Excess l-glutamate (glutamate) levels in brain interstitial and cerebrospinal fluids (ISF and CSF, respectively) are the hallmark of several neurodegenerative conditions such as stroke, traumatic brain injury or amyotrophic lateral sclerosis. Its removal could prevent the glutamate excitotoxicity that causes long-lasting neurological deficits. As in previous studies, we have established the role of blood glutamate levels in brain neuroprotection, we have now investigated the contribution of the peripheral organs to the homeostasis of glutamate in blood. We have administered naive rats with intravenous injections of either l-[1-¹⁴C] Glutamic acid (l-[1-¹⁴C] Glu), l-[G-³H] Glutamic acid (l-[G-³H] Glu) or d-[2,3-³H] Aspartic acid (d-[2,3-³H] Asp), a non-metabolized analog of glutamate, and have followed their distribution into peripheral organs. We have observed that the decay of the radioactivity associated with l-[1-¹⁴C] Glu and l-[G-³H] Glu was faster than that associated with glutamate non-metabolized analog, d-[2,3-³H] Asp. l-[1-¹⁴C] Glu was subjected in blood to a rapid decarboxylation with the loss of ¹⁴CO₂. The three major sequestrating organs, serving as depots for the eliminated glutamate and/or its metabolites were skeletal muscle, liver and gut, contributing together 92% or 87% of total l-[U-¹⁴C] Glu or d-[2,3-³H] Asp radioactivity capture. l-[U-¹⁴C] Glu and d-[2,3-³H] Asp showed a different organ sequestration pattern. We conclude that glutamate is rapidly eliminated from the blood into peripheral tissues, mainly in non-metabolized form. The liver plays a central role in glutamate metabolism and serves as an origin for glutamate metabolites that redistribute into skeletal muscle and gut. The findings of this study suggest now that pharmacological manipulations that reduce the liver glutamate release rate or cause a boosting of the skeletal muscle glutamate pumping rate are likely to cause brain neuroprotection.     

Synthesis of triazole Schiff bases: Novel inhibitors of nucleotide pyrophosphatase/phosphodiesterase-1

A series of Schiff base triazoles 1–25 was synthesized and evaluated for their nucleotide pyrophosphatase/phosphodiesterase-1 inhibitory activities. Among twenty-five compounds, three compounds 10 (IC₅₀ = 132.20 ± 2.89 μM), 13 (IC₅₀ = 152.83 ± 2.39 μM), and 22 (IC₅₀ = 251.0 ± 6.64 μM) were identified as potent inhibitors with superior activities than the standard EDTA (IC₅₀ = 277.69 ± 2.52 μM). The newly identified inhibitors may open a new avenue for the development of treatment of phosphodiesterase-I related disorders. These compounds were also evaluated for carbonic anhydrase, acetylcholinesterase and butyrylcholinesterase inhibitory potential and were found to be inactive. The compounds showed non-toxic effect towards PC3 cell lines.     

From d-xylose to terminal polyols: a simple synthetic route

A simple and efficient synthetic approach toward different terminal alkyl tetraols and triols, starting from d-xylose, is described. The opening of the oxetane ring in a suitably protected 3,5-anhydro-d-xylose derivative with Grignard reagents leads to d-xylose-derived 5-deoxy-5-C-alkyl derivatives, which are suitable for reduction to terminal polyols after protecting group hydrolysis.     

Synthesis of seleno-carbohydrates derived from d-galactose

The synthesis of seleno-galactopyranosides in a short and efficient manner is described, starting from the parent carbohydrate d-galactose. The approach described allows the synthesis of small libraries of compounds with a number of structural variations at the group attached to selenium. Compounds with aryl, propargyl, allyl, acyl, and alkyl substituents are described.     

Antibacterial Co(II), Ni(II), Cu(II) and Zn(II) Complexes of Schiff bases Derived from Fluorobenzaldehyde and Triazoles

Antibacterial Schiff bases derived from 1,2,4-triazoles as well as their metal complexes incorporating cobalt(II), nickel(II), copper(II) and zinc(II) have been synthesized and characterized. Physico-chemical studies suggest that an octahedral geometry for the cobalt(II), nickel(II) and zinc(II)and square-planer geometry for the copper(II) complexes. These complexes have been screened for antibacterial activity against three Gram-positive (Staphylococcus aureus, Staphylococcus epidermidis and Bacillus subtilis) and two Gram-negative (Salmonella typhi and Pseudomonas aeruginosa) bacterial strains, and results compared with the activity of the free ligands. The metal complexes were found to be more potent against one or more bacterial strains than the free ligands.     

Preparation and characterisation of oxovanadium(IV) complexes derived from 2,6-diformyl-4-methylphenol and l-His and l-Ala. Spectroscopic study of the system VO + BDF-His

By reaction of 2,6-diformyl-4-methylphenol (BDF) with the amino acids l-His and l-Ala in the presence of VOCl₂, two new oxovanadium(IV) complexes with the ligand obtained by the 1:2 condensation of BDF with the amino acids, BDF-His and BDF-Ala, were synthesised. The compounds were characterised in the solid state by elemental analyses, IR, CD and magnetic susceptibility measurements, and in the mother liquor by EPR. In water-containing solutions, BDF-Ala and BDF-His partially hydrolyse but the degree of Schiff base formation increases upon addition of VOSO₄. The equilibria in the system V^IVO²⁺ + BDF-His were studied by spectroscopic methods (EPR, CD and UV-Vis) in the pH range 1.5-12. The coordination behaviour of the ligand changes as the pH increases, leading to the formation of four main species all involving O_phen as donor atom. Plausible binding modes are discussed based on the spectroscopic results.