RESUMEN

Three dinuclear zinc(II) acetate complexes of the general formula [Zn{Ln}(AcO)]2, namely, di-µ-acetato-κ4O:O'-bis[({2-[(pyridin-2-ylmethylidene)amino]phenyl}sulfanido-κ3N,N',S)zinc(II)], [Zn2(C12H9N2S)2(C2H3O2)2] (n = 1), 4, µ-acetato-1:2κ2O:O'-acetato-2κO-[µ-(2-{[1-(pyridin-2-yl)ethylidene]amino}phenyl)sulfanido-1κS:2κ3N,N',S][(2-{[1-(pyridin-2-yl)ethylidene]amino}phenyl)sulfanido-1κ3N,N',S]dizinc(II), [Zn2(C13H11N2S)2(C2H3O2)2] (n = 2), 5, and µ-acetato-1:2κ2O:O'-acetato-2κO-[µ-(2-{[phenyl(pyridin-2-yl)methylidene]amino}phenyl)sulfanido-1κS:2κ3N,N',S][(2-{[phenyl(pyridin-2-yl)methylidene]amino}phenyl)sulfanido-1κ3N,N',S]dizinc(II)-bis(2-aminophenyl) disulfide (2/1), [Zn2(C18H13N2S)2(C2H3O2)2]·0.5C12H12N2S2 (n = 3), 6·0.5(2-APS)2, were obtained from the reaction of 2-R-(pyridin-2-yl)benzothiazoline precursors (R = H, 1; R = Me, 2; R = Ph, 3) with zinc acetate dihydrate in a 1:1 ratio. All the complexes crystallized as dinuclear species and complex 6 cocrystallized with one molecule of bis(2-aminophenyl) disulfide (2-APS)2. The anionic Schiff base ligands {Ln}- displayed a κ2N,κS-tridentate coordination mode with the formation of two five-membered chelate rings. In 4, 5 and 6·0.5(2-APS)2, both ZnII ions are pentacoordinated and the coordination sphere of 4 was different with respect to those in 5 and 6·0.5(2-APS)2. For 4, the X-ray diffraction study showed a dinuclear complex containing two bridging acetate ligands linked to both ZnII ions. For 5 and 6·0.5(2-APS)2, the dinuclear complexes displayed one bridging acetate ligand linked to both ZnII ions, where the first ZnII ion includes a dative bond with one S atom from an adjacent anionic Schiff base {Ln}-, while the second ZnII ion is coordinated to one terminal acetate ligand. In each dinuclear complex, the geometry is the same for both ZnII metal centres. The local geometry of the ZnII cation in 4 is halfway between trigonal bipyramidal and square pyramidal local geometries; in 5 and 6, the local geometries are described as distorted square pyramidal. Hirshfeld surface analysis of 5 and 6 showed the predominance of H...H interactions, as well as the contribution of C-H...C, C-H...O and C-H...S noncovalent interactions to the cohesion of the crystalline network of the ZnII complexes.

RESUMEN

BACKGROUND: Currently, there is no antiviral licensed to treat chikungunya fever, a disease caused by the infection with Alphavirus chikungunya (CHIKV). Treatment is based on analgesic and anti-inflammatory drugs to relieve symptoms. Our study aimed to evaluate the antiviral activity of sulfadoxine (SFX), an FDA-approved drug, and its derivatives complexed with silver(I) (AgSFX), salicylaldehyde Schiff base (SFX-SL), and with both Ag and SL (AgSFX-SL) against CHIKV. METHODS: The anti-CHIKV activity of SFX and its derivatives was investigated using BHK-21 cells infected with CHIKV-nanoluc, a marker virus-carrying nanoluciferase reporter. Dose-response and time of drug-addition assays were performed in order to assess the antiviral effects of the compounds, as well as in silico data and ATR-FTIR analysis for insights on their mechanisms of action. RESULTS: The SFX inhibited 34% of CHIKV replication, while AgSFX, SFX-SL, and AgSFX-SL enhanced anti-CHIKV activity to 84%, 89%, and 95%, respectively. AgSFX, SFX-SL, and AgSFX-SL significantly decreased viral entry and post-entry to host cells, and the latter also protected cells against infection. Additionally, molecular docking calculations and ATR-FTIR analysis demonstrated interactions of SFX-SL, AgSFX, and AgSFX-SL with CHIKV. CONCLUSIONS: Collectively, our findings suggest that the addition of metal ions and/or Schiff base to SFX improved its antiviral activity against CHIKV.

Asunto(s)

Antivirales , Fiebre Chikungunya , Virus Chikungunya , Sulfadoxina , Virus Chikungunya/efectos de los fármacos , Antivirales/farmacología , Antivirales/química , Animales , Línea Celular , Sulfadoxina/farmacología , Fiebre Chikungunya/tratamiento farmacológico , Fiebre Chikungunya/virología , Cricetinae , Bases de Schiff/farmacología , Plata/farmacología , Plata/química , Replicación Viral/efectos de los fármacos , Simulación del Acoplamiento Molecular , Relación Dosis-Respuesta a Droga , Humanos , Aldehídos

RESUMEN

An innovative supramolecular architecture is reported for bienzymatic glucose biosensing based on the use of a nanohybrid made of multi-walled carbon nanotubes (MWCNTs) non-covalently functionalized with a Schiff base modified with two phenylboronic acid residues (SB-dBA) as platform for the site-specific immobilization of the glycoproteins glucose oxidase (GOx) and horseradish peroxidase (HRP). The analytical signal was obtained from amperometric experiments at - 0.050 V in the presence of 5.0 × 10-4 M hydroquinone as redox mediator. The concentration of GOx and HRP and the interaction time between the enzymes and the nanohybrid MWCNT-SB-dBA deposited at glassy carbon electrodes (GCEs) were optimized through a central composite design (CCD)/response surface methodology (RSM). The optimal concentrations of GOx and HRP were 3.0 mg mL-1 and 1.50 mg mL-1, respectively, while the optimum interaction time was 3.0 min. The bienzymatic biosensor presented a sensitivity of (24 ± 2) × 102 µA dL mg-1 ((44 ± 4) × 102 µA M-1), a linear range between 0.06 mg dL-1 and 21.6 mg dL-1 (3.1 µM-1.2 mM) (R2 = 0.9991), and detection and quantification limits of 0.02 mg dL-1 (1.0 µM) and 0.06 mg dL-1 (3.1 µM), respectively. The reproducibility for five sensors prepared with the same MWCNT-SB-dBA nanohybrid was 6.3%, while the reproducibility for sensors prepared with five different nanohybrids and five electrodes each was 7.9%. The GCE/MWCNT-SB-dBA/GOx-HRP was successfully used for the quantification of glucose in artificial human urine and commercial human serum samples.

Asunto(s)

Técnicas Biosensibles , Ácidos Borónicos , Enzimas Inmovilizadas , Glucosa Oxidasa , Peroxidasa de Rábano Silvestre , Nanotubos de Carbono , Bases de Schiff , Nanotubos de Carbono/química , Bases de Schiff/química , Técnicas Biosensibles/métodos , Ácidos Borónicos/química , Glucosa Oxidasa/química , Glucosa Oxidasa/metabolismo , Peroxidasa de Rábano Silvestre/química , Peroxidasa de Rábano Silvestre/metabolismo , Humanos , Enzimas Inmovilizadas/química , Enzimas Inmovilizadas/metabolismo , Glucosa/análisis , Electrodos , Límite de Detección , Técnicas Electroquímicas/métodos , Glucemia/análisis

RESUMEN

The PdII complex bis-{(S)-(-)-N-[(biphenyl-2-yl)methyl-idene]1-(4-meth-oxy-phen-yl)ethanamine-κN}di-chlorido-palladium(II), [PdCl2(C22H21NO)2], crystallizes in the monoclinic Sohncke space group P21 with a single mol-ecule in the asymmetric unit. The coordination environment around the palladium is slightly distorted square planar. The N-Pd-Cl bond angles are 91.85 (19), 88.10 (17), 89.96 (18), and 90.0 (2)°, while the Pd-Cl and Pd-N bond lengths are 2.310 (2) and 2.315 (2) Šand 2.015 (2) and 2.022 (6) Å, respectively. The crystal structure features inter-molecular N-H⋯Cl and intramolecular C-H⋯Pd inter-actions, which lead to the formation of a supramolecular framework structure.

RESUMEN

In this study, we report the synthesis and characterization of pH-responsive nanoconjugates for targeted drug delivery. Galactomannan extracted from D. regia seeds was oxidized to form aldehyde groups, achieving a percentage of oxidation of 25.6 %. The resulting oxidized galactomannan (GMOX) was then copolymerized with PINIPAm-NH2, yielding a copolymer. The copolymer exhibited signals from both GMOX and PNIPAm-NH2 in its NMR spectrum, confirming successful copolymerization. Critical association concentration (CAC) studies revealed the formation of nanostructures, with lower CAC values observed at higher temperatures. The copolymer and GMOX reacted with doxorubicin (DOX), resulting in nanoconjugates with controlled drug release profiles, especially under acidic conditions similar to tumor microenvironments. Cytotoxicity assays demonstrated significant efficacy of the nanoconjugates against melanoma cells with reduced toxicity towards healthy cells. These findings underscore the potential of the pH-responsive nanoconjugates as promising candidates for targeted cancer therapy, offering improved therapeutic efficacy and reduced systemic side effects.

Asunto(s)

Doxorrubicina , Galactosa , Mananos , Nanoconjugados , Doxorrubicina/farmacología , Doxorrubicina/química , Mananos/química , Mananos/farmacología , Galactosa/química , Galactosa/análogos & derivados , Humanos , Nanoconjugados/química , Concentración de Iones de Hidrógeno , Liberación de Fármacos , Línea Celular Tumoral , Portadores de Fármacos/química , Supervivencia Celular/efectos de los fármacos , Antibióticos Antineoplásicos/farmacología , Antibióticos Antineoplásicos/química , Antineoplásicos/química , Antineoplásicos/farmacología

RESUMEN

The (S)-(+)-1-(4-bromo-phen-yl)-N-[(4-methoxyphen-yl)methyl-idene]ethyl-amine ligand, C16H16BrNO, (I), was synthesized through the reaction of 4-meth-oxy-anisaldehyde with (S)-(-)-1-(4-bromo-phen-yl)ethyl-amine. It crystallizes in the ortho-rhom-bic space group P212121 belonging to the Sohncke group, featuring a single mol-ecule in the asymmetric unit. The refinement converged successfully, achieving an R factor of 0.0508. The PdII com-plex bis-{(S)-(+)-1-(4-bromo-phen-yl)-N-[(4-methoxyphen-yl)methyl-idene]ethyl-amine-κN}di-chlorido-pal-ladium(II), [PdCl2(C16H16BrNO)2], (II), crystallizes in the monoclinic space group P21 belonging to the Sohncke group, with two mol-ecules in the asymmetric unit. The central atom is tetra-coordinated by two N atoms and two Cl atoms, resulting in a square-planar configuration. The imine moieties exhibit a trans configuration around the PdII centre, with average Cl-Pd-N angles of approximately 89.95 and 90°. The average distances within the palladium com-plex for the two mol-ecules are ∼2.031 Šfor Pd-N and ∼2.309 Šfor Pd-Cl.

RESUMEN

Copper(II) complexes are interesting for cancer treatment due to their unique properties, including their redox potential, possible coordination structures with different ligands, the most diverse geometries, and different biomolecule reactivity. The present work synthesized new copper(II) complexes with Schiff-base (imine) type ligands using natural aldehydes such as cinnamaldehyde, vanillin, or ethyl vanillin. The ligands were obtained through the reaction of these aldehydes with the amines 1,3-diaminopropane, 2,2-dimethyl-1,3-propanediamine, or 1,3-diamino-2-propanol and characterized by 1H and 13C NMR, FTIR and ESI-HRMS. The complexation reaction used copper(II) as perchlorate salt, obtaining six new copper(II) complexes. The complexes were characterized using FTIR, UV-vis, elemental analysis, ESI-HRMS, and EPR. In addition, the interaction with the copper(II) complexes and serum albumin was investigated by electronic absorption, showing complex incorporation in the albumin structure. The cytotoxicity of the complexes was evaluated using MTT assay in neuroblastoma cell lines SH-SY5Y, CHP 212, and glioblastoma LN-18, and presented EC50 values between 90 and 300 µM. Based on our results, a square-planar copper(II) complex derived from Schiff-base cinnamaldehyde was found here to possess significant potential as an anti-cancer treatment. Further investigation is required to explore this compound's benefits in cancer co-treatment approaches fully.

Asunto(s)

Complejos de Coordinación , Neuroblastoma , Humanos , Cobre/química , Espectroscopía de Resonancia Magnética , Acroleína/farmacología , Bases de Schiff/química , Complejos de Coordinación/química , Ligandos

RESUMEN

In the search for new 5-LOX inhibitors, two ferrocenyl Schiff base complexes functionalized with catechol ((ƞ5-(E)-C5H4-NCH-3,4-benzodiol)Fe(ƞ5-C5H5) (3a)) and vanillin ((ƞ5-(E)-C5H4-NCH-3-methoxy-4-phenol)Fe(ƞ5-C5H5) (3b)) were obtained. Complexes 3a and 3b were biologically evaluated as 5-LOX inhibitors showed potent inhibition compared to their organic analogs (2a and 2b) and known commercial inhibitors, with IC50 = 0.17 ± 0.05 µM for (3a) and 0.73 ± 0.06 µM for (3b) demonstrated a highly inhibitory and potent effect against 5-LOX due to the incorporation of the ferrocenyl fragment. Molecular dynamic studies showed a preferential orientation of the ferrocenyl fragment toward the non-heme iron of 5-LOX, which, together with electrochemical and in-vitro studies, allowed us to propose a competitive redox deactivation mechanism mediated by water, where Fe(III)-enzyme can be reduced by the ferrocenyl fragment. An Epa/IC50 relationship was observed, and the stability of the Schiff bases was evaluated by SWV in the biological medium, observing that the hydrolysis does not affect the high potency of the complexes, making them interesting alternatives for pharmacological applications.

Asunto(s)

Araquidonato 5-Lipooxigenasa , Bases de Schiff , Bases de Schiff/farmacología , Bases de Schiff/química , Araquidonato 5-Lipooxigenasa/química , Araquidonato 5-Lipooxigenasa/metabolismo , Compuestos Férricos , Simulación de Dinámica Molecular , Oxidación-Reducción , Inhibidores de la Lipooxigenasa/farmacología , Relación Estructura-Actividad

RESUMEN

Cu(II) complexes bearing NNO-donor Schiff base ligands (2a, b) have been synthesized and characterized. The single crystal X-ray analysis of the 2a complex revealed that a mononuclear and a dinuclear complex co-crystallize in the solid state. The electronic structures of the complexes are optimized by Density Functional Theory (DFT) calculations. The monomeric nature of 2a and 2b species is maintained in solution. Antioxidant activities of the ligands (1a, b) and Cu(II) complexes (2a, b) were determined by in vitro assays such as 1,1-diphenyl-2-picrylhydrazyl free radicals (DPPH.) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radicals (ABTS+). Our results demonstrated that 2a showed better antioxidant activity. MTT assays were performed to assess the toxicity of ligands and Cu(II) complexes in V79 cells. The antiproliferative activity of compounds was tested against two human tumor cell lines: MCF-7 (breast adenocarcinoma) and SW620 (colorectal carcinoma) and on MRC-5 (normal lung fibroblast). All compounds showed high cytotoxicity in the all-cell lines but showed no selectivity for tumor cell lines. Antiproliferative activity by clonogenic assay 2b showed a more significant inhibitory effect on the MCF-7 cell lines than on MRC-5. DNA damage for the 2b compound at 10 µM concentration was about three times higher in MCF-7 cells than in MRC-5 cells.

RESUMEN

We synthesize and characterize nine copper(II) compounds. Four with general formula [Cu(NNO)(NO3)] and five mixed chelates [Cu(NNO)(N-N)]+, where NNO corresponds to asymmetric salen ligands (E)-2-((2-(methylamino)ethylimino)methyl)phenolate (L1) and (E)-3-((2-(methylamino)ethylimino)methyl)naphthalenolate (LN1); and their hydrogenated derivatives 2-((2-(methylamino)ethylamino)methyl)phenolate (LH1) and 3-((2-(methylamino)ethylamino)methyl)naphthalenolate (LNH1); and N-N correspond to 4,4'-dimethyl-2,2'-bipiridyne(dmbpy) or 1,10-phenanthroline (phen). Using EPR, the geometries of the compounds in solution in DMSO were assigned, [Cu(LN1)(NO3)] and [Cu(LNH1)(NO3)] a square-planar, [Cu(L1)(NO3)], [Cu(LH1)(NO3)], [Cu(L1)(dmby)]+ and [Cu(LH1)(dmby)]+ a square-based pyramid; and [Cu(LN1)(dmby)]+, [Cu(LNH1)(dmby)]+ and [Cu(L1)(phen)]+ and elongated octahedral. By X-ray it was observed that [Cu(L1)(dmby)]+ and. [Cu(LN1)(dmby)]+ presented a square-based pyramidal, and [Cu(LN1)(NO3)]+ a square-planar geometry. The electrochemical study showed that copper reduction process is a quasi-reversible system, where the complexes with hydrogenated ligands were less oxidizing. The cytotoxicity of the complexes was tested by MTT assay, all the compounds showed biological activity in HeLa cell line, the mixed compounds were the more active ones. Naphthalene moiety, imine hydrogenation and aromatic diimine coordination, increased biological activity. A structure-activity relationships were found: Log(IC50) =  - 1.01(Epc) - 0.35(Conjugated Rings) + 0.87, for Schiff base complexes and Log(IC50) = 0.078(Epc) - 0.32(Conjugated Rings) + 1.94, for hydrogenated complexes; the less oxidizing species with a great number of conjugated rings presented the best biological activity. Complexes-DNA binding constants were obtained by uv-vis studies using CT-DNA, the results suggested that the complexes can interact through the grooves, except the phenanthroline mixed complex that intercalate with DNA. Gel electrophoresis study with pBR 322 showed that compounds can produce changes in the form of DNA and some complexes can cleave DNA in the presence of H2O2.

Asunto(s)

Complejos de Coordinación , Bases de Schiff , Humanos , Bases de Schiff/farmacología , Bases de Schiff/química , Cobre/química , Células HeLa , Peróxido de Hidrógeno , ADN/química , Complejos de Coordinación/farmacología , Complejos de Coordinación/química , Ligandos , Cristalografía por Rayos X

RESUMEN

In this manuscript, the synthesis of enamine-type Schiff bases 1−48 derived from the amino acids L-Ala, L-Tyr, and L-Phe was carried out. Their in vitro activity and in vivo protective effect against Fusarium oxysporum were also evaluated through mycelial growth inhibition and disease severity reduction under greenhouse conditions. The in vitro activity of test compounds 1−48 showed half-maximal inhibitory concentrations (IC50) at different levels below the 40 mM range. Deep analysis of the IC50 variations indicated that the size of the substituent on the acetylacetone derivatives and the electronic character on the cyclohexane-3-one fragment influenced the antifungal effect. 3D-QSAR models based on atoms (atom-based approach) were built to establish the structure−activity relationship of the test Schiff bases, showing a good correlation and predictive consistency (R2 > 0.70 and Q2 > 0.60). The respective contour analysis also provided information about the structural requirements for potentiating their antifungal activity. In particular, the amino acid-related fragment and the alkyl ester residue can favor hydrophobic interactions. In contrast, the nitrogen atoms and enamine substituent are favorable regions as H-donating and electron-withdrawing moieties. The most active compounds (40 and 41) protected cape gooseberry plants against F. oxysporum infection (disease severity index < 2), involving adequate physiological parameters (stomatal conductance > 150 mmol/m2s) after 45 days of inoculation. These promising results will allow the design of novel Schiff base-inspired antifungals using 2-amino acids as precursors.

RESUMEN

Abstract Schiff bases are aldehyde-or ketone-like chemical compounds in which an imine or azomethine group replaces the carbonyl group. Such compounds show various beneficial biological activities, such as anti-inflammation and antioxidants. The present study addresses comprehensiveevaluation of antidiabetic effect of two novel dibromides and dichlorides substituted Schiff bases substituted Schiff bases (2,2'-[1,2-cyclohexanediylbis (nitriloethylidyne)]bis[4-chlorophenol] (CNCP) and 2, 2'-[1,2-cyclohexanediylbis(nitriloethylidyne)]bis[4-bromophenol] (CNBP) with two different doses, high (LD) and low (LD) in streptozotocin and nicotinamide induced diabetic rats. The rats were separated into normal, untreated, treated and reference groups. Except for the normal group, diabetes traits were induced in the rest animals. Insulin level was measured, and the effect of the compounds on biochemical parameters of liver function and lipid profile were evaluated. High glucose and decreased insulin level are observed in the groups. The histological evaluation confirms that the hepatic architecture in the treated animals with a low dose of CNCP is quite similar to that of the normal hepatic structure and characterized by normal central vein, hepatocytes without any fatty alterations and mild red blood cell infiltration. CNCP (LD) and CNBP (HD) are more successful in enhancing cell survival in the diabetic rat's liver and can be responsible for causing much healthier structure and notable morphology improvement.

Asunto(s)

Animales , Masculino , Ratas , Bases de Schiff/agonistas , Estreptozocina/antagonistas & inhibidores , Hipoglucemiantes/efectos adversos , Nicotinamidasa/antagonistas & inhibidores

RESUMEN

The first neutral 2D heterometallic assemblies based on orbitally degenerate heptacyanidorhenate(IV) were prepared and structurally characterized. An analysis of the magnetic data for the polycrystalline samples of Ph4P[{Mn(acacen)}2Re(CN)7]·Solv (1) and PPN[{Mn(acacen)}2Re(CN)7]·Solv (2) have shown that both materials display slow magnetic relaxation at temperatures below 10 and 21 K for 1 and 2, respectively. Despite the presence of the same molecular magnetic modules that make up the anionic layers, the studied 2D networks differ significantly in magnetic anisotropy, having a small coercive field (0.115 T) for 1 and a large one (~2.5 T) for 2 at 2 K. In addition, for both polymers a M(H) value does not saturate at the maximum available field of 7 T, and the material 2 is a metamagnet. This intriguing difference originates from the cooperative anisotropic spin interaction in ReIV-CN-MnIII pairs and the zero field splitting (ZFS) effect of MnIII ions with a noncollinear alignment of the local magnetic axes in crystals of the compounds.

RESUMEN

Nowadays, antimicrobial resistance is a serious concern associated with the reduced efficacy of traditional antibiotics and an increased health burden worldwide. In response to this challenge, the scientific community is developing a new generation of antibacterial molecules. Contributing to this effort, and inspired by the resveratrol structure, five new resveratrol-dimers (9a−9e) and one resveratrol-monomer (10a) were synthetized using 2,5-dibromo-1,4-diaminobenzene (8) as the core compound for Schiff base bridge conformation. These compounds were evaluated in vitro against pathogenic clinical isolates of Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus sp., and Listeria monocytogenes. Antibacterial activity measurements of resveratrol-Schiff base derivatives (9a−9e) and their precursors (4−8) showed high selectivity against Listeria monocytogenes, being 2.5 and 13.7 times more potent than chloramphenicol, while resveratrol showed an EC50 > 320 µg/mL on the same model. Moreover, a prospective mechanism of action for these compounds against L. monocytogenes strains was proposed using molecular docking analysis, finding a plausible inhibition of internalin C (InlC), a surface protein relevant in bacteria−host interaction. These results would allow for the future development of new molecules for listeriosis treatment based on compound 8.

RESUMEN

A tetra-nuclear complex with an open-cubane-like core structure was synthesized from 2-meth-oxy-6-(pyridin-2-yl-hydrazonometh-yl)phenol (HL), namely, cyclo-tetra-kis-(µ-2-meth-oxy-6-{[2-(pyridin-2-yl)hydrazin-1-yl-idene]meth-yl}pheno-lato)tetra-nickel(II) tetra-kis-(perchlorate) aceto-nitrile monosolvate dihydrate, [Ni4(C13H12N3O2)4](ClO4)4·C2H3N·2H2O, and characterized using micro-analytical and spectroscopic techniques. The crystal-structure determination reveals the formation of a distorted Ni4O4 cubane-like core architecture encapsulated by four hydrazone Schiff base (HL) mol-ecules. A open-cube tetra-nuclear architecture is created in which nickel(II) ions of the NiN2O3 unit are connected by µ2-O anions of the phenolate moiety of HL. In this complex, each Ni centre has a slightly distorted square-pyramidal coordination environment. The supra-molecular architectures are stabilized via the presence of various inter-molecular hydrogen bonds and (ar-yl-aryl, ar-yl-chelate and chelate-chelate) stacking inter-actions.

RESUMEN

The use of schiff base complex against microbial agentes a has recently received more attention as a strategy to combat infections caused by multidrug-resistant bacteria and leishmania. This study aimed to evaluate the toxicity, antibacterial and leishmanicidal activities of the nickel (II) chloride schiff base complex ([Ni(L2)] against Leishmania amazonensis promastigote, multi-resistant bacterial strains and evaluate to modulate antibiotic activity against multi-resistant bacterial. The schiff base complex was characterized by the techniques of elemental analysis, Fourier transform infrared spectroscopy (FTIR), UV-vis absorption spectroscopy and thermal analysis (TGA/DTG/DSC). The [Ni(L2)] complex presented moderate toxicity in saline artemia (LC50 = 150.8 µg/mL). In leishmanicidal assay, the NiL2 complex showed values of IC50 of (6.079 µg/mL ± 0.05656 at the 24 h), (0.854 µg/mL ± 0.02474, 48 h) and (1.076 µg/mL ± 0.04039, 72 h). In antibacterial assay, the [Ni(L2)] complex presented significant inhibited the bacterial growth of P. aeruginosa (MIC = 256 µg/mL). However, [Ni(L2)] complex did not present clinically relevant minimum inhibitory concentration (MIC ≥1024 µg/mL) against S. aureus and E. coli. The combination of [Ni(L2)] complex and antibacterial drugs resulted in the increased antibiotic activity of gentamicin and amikacin against S. aureus and E.coli multi-resistant strains. Thus, our results showed that [Ni(L2)] complex is a promising molecule for the development of new therapies associated with aminoglycoside antibiotics and in disease control related to resistant bacteria and leishmaniasis.

Asunto(s)

Antibacterianos/farmacología , Complejos de Coordinación/farmacología , Bases de Schiff/farmacología , Tripanocidas/farmacología , Amicacina/farmacología , Animales , Antibacterianos/química , Artemia/efectos de los fármacos , Complejos de Coordinación/química , Sinergismo Farmacológico , Escherichia coli/efectos de los fármacos , Gentamicinas/farmacología , Leishmania infantum/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Níquel/química , Pruebas de Sensibilidad Parasitaria , Pseudomonas aeruginosa/efectos de los fármacos , Bases de Schiff/química , Staphylococcus aureus/efectos de los fármacos , Tripanocidas/química

RESUMEN

A new series of ten examples of Schiff bases, namely (E)-2-(((2-alkyl(aryl/heteroaryl)-4-(trifluoromethyl)quinolin-6-yl)imino)methyl)phenols 3, was easily synthesized with yields of up to 91% from the reactions involving a series of 2-(R-substituted) 6-amino-4-(trifluoromethyl)quinolines 1 and 4(5)-R1-substituted salicylaldehydes 2 - in which alkyl/aryl/heteroaryl for 2-R-substituents are Me, Ph, 4-MeC6H4, 4-FC6H4, 4-NO2C6H4, and 2-furyl, and R1-substituents are 5-NEt2, 5-OCH3, 4-Br, and 4-NO2. Complementarily, the Schiff bases showed low to good quantum fluorescence yield values in CHCl3 (Φf = 0.12-0.80), DMSO (Φf = 0.20-0.75) and MeOH (Φf = 0.13-0.85). Higher values of Stokes shifts (SS) were observed in more polar solvents (DMSO; 65-150 nm and MeOH; 65-130 nm) than in CHCl3 (59-85 nm). Compounds 3 presented good stability under white-LED irradiation conditions and moderate ROS generation properties were observed.

RESUMEN

New porphyrin-Schiff base conjugates bearing one (6) and two (7) basic amino groups were synthesized by condensation between tetrapyrrolic macrocycle-containing amine functions and 4-(3-(N,N-dimethylamino)propoxy)benzaldehyde. This approach allowed us to easily obtain porphyrins substituted by positive charge precursor groups in aqueous media. These compounds showed the typical Soret and four Q absorption bands with red fluorescence emission (ΦF ~ 0.12) in N,N-dimethylformamide. Porphyrins 6 and 7 photosensitized the generation of O2(1Δg) (ΦΔ ~ 0.44) and the photo-oxidation of L-tryptophan. The decomposition of this amino acid was mainly mediated by a type II photoprocess. Moreover, the addition of KI strongly quenched the photodynamic action through a reaction with O2(1Δg) to produce iodine. The photodynamic inactivation capacity induced by porphyrins 6 and 7 was evaluated in Staphylococcus aureus, Escherichia coli, and Candida albicans. Furthermore, the photoinactivation of these microorganisms was improved using potentiation with iodide anions. These porphyrins containing basic aliphatic amino groups can be protonated in biological systems, which provides an amphiphilic character to the tetrapyrrolic macrocycle. This effect allows one to increase the interaction with the cell wall, thus improving photocytotoxic activity against microorganisms.

Asunto(s)

Aminoácidos Básicos/química , Antiinfecciosos/farmacología , Antifúngicos/farmacología , Candida albicans/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Porfirinas/química , Bases de Schiff/farmacología , Antiinfecciosos/química , Antifúngicos/química , Bases de Schiff/química

RESUMEN

We have recently reported a series of neutral square planar tridentate Schiff base (L) complexes of the general formula [(L)M(py)], showing relatively high first-order hyperpolarizabilities and NLO redox switching behavior. In the present study, new members of this family of compounds have been prepared with the objective to investigate their potential as building blocks in the on-demand construction of D-π-A push-pull systems. Namely, ternary nickel(II) building blocks of general formula [(LA/D)Ni(4-pyX)] (4-7), where LA/D stands for an electron accepting or donating dianionic O,N,O-tridentate Schiff base ligand resulting from the monocondensation of 2-aminophenol or its 4-substituted nitro derivative and ß-diketones R-C(=O)CH2C(=O)CH3 (R = methyl, anisyl, ferrocenyl), and 4-pyX is 4-iodopyridine or 4-ethynylpyridine, were synthesized and isolated in 60-78% yields. Unexpectedly, the Sonogashira cross-coupling reaction between the 4-iodopyridine derivative 6 and 4-ethynylpyridine led to the formation of the bis(4-pyridyl) acetylene bridged centrosymmetric dimer [{(LD)Ni}2(µ2-py-C≡C-py)] (8). Complexes 4-8 were characterized by elemental analysis, FT-IR and NMR spectroscopy, single crystal X-ray diffraction and computational methods. In each compound, the four-coordinate Ni(II) metal ion adopts a square planar geometry with two nitrogen and two oxygen atoms as donors occupying trans positions. In 8, the Ni…Ni separation is of 13.62(14) Å. Experimental results were proved and explained theoretically exploiting Density Functional Theory calculations.

RESUMEN

Biological membranes are complex dynamic systems composed of a great variety of carbohydrates, lipids, and proteins, which together play a pivotal role in the protection of organisms and through which the interchange of different substances is regulated in the cell. Given the complexity of membranes, models mimicking them provide a convenient way to study and better understand their mechanisms of action and their interactions with biologically active compounds. Thus, in the present study, a new Schiff base (Bz-Im) derivative from 2-(m-aminophenyl)benzimidazole and 2,4-dihydroxybenzaldehyde was synthesized and characterized by spectroscopic and spectrometric techniques. Interaction studies of (Bz-Im) with two synthetic membrane models prepared with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and DMPC/1,2-dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG) 3:1 mixture, imitating eukaryotic and prokaryotic membranes, respectively, were performed by applying differential scanning calorimetry (DSC). Molecular dynamics simulations were also developed to better understand their interactions. In vitro and in silico assays provided approaches to understand the effect of Bz-Im on these lipid systems. The DSC results showed that, at low compound concentrations, the effects were similar in both membrane models. By increasing the concentration of Bz-Im, the DMPC/DMPG membrane exhibited greater fluidity as a result of the interaction with Bz-Im. On the other hand, molecular dynamics studies carried out on the erythrocyte membrane model using the phospholipids POPE (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine), SM (N-(15Z-tetracosenoyl)-sphing-4-enine-1-phosphocholine), and POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) revealed that after 30 ns of interaction, both hydrophobic interactions and hydrogen bonds were responsible for the affinity of Bz-Im for PE and SM. The interactions of the imine with POPG (1-Palmitoyl-2-Oleoyl-sn-Glycero-3-Phosphoglycerol) in the E. coli membrane model were mainly based on hydrophobic interactions.