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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 279: 121429, 2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-35653808

RESUMO

Three new phenanthroline-derived ligands were synthesized by the Schiff base condensation method. The first ligand was the result of 1,10-phenanthroline-2-carboxyaldehyde reaction with 1,4-diaminobutane (L1). The other ligands were obtained 1,6-diaminohexane (L2) and 1,8-diaminooctane (L3) with the phenanthroline aldehyde in separate reactions. The structures of all ligands were elucidated using spectral techniques such as FT-IR, 13C NMR, 1H NMR and LC ESI/MS. The geometric properties of ligands such as bond lengths, bond angles, dihedral angles, electronic properties, HOMO and LUMO energies were calculated by using the Gaussian 09w programme. Ligands were optimized with B3LYP and 6-311++G(2d,p) basis set and NMR and FT-IR spectra were calculated. Experimental and theoretical spectrum data were compared. All of the ligands showed antibacterial activity against Staphylococcus aureus ATCC 25923 and Bacillus cereus ATCC 11778. The anticancer activities of the ligands were also determined against human breast cancer (MCF7) and prostate cancer (DU145) cell lines. In addition, which conformation of the ligands was determined by the theoretical calculations. Docking studies of ligands with bovine serum albumin (BSA) were performed using Autock Tools 1.5.6 programme.


Assuntos
Fenantrolinas , Bases de Schiff , Humanos , Ligantes , Simulação de Acoplamento Molecular , Fenantrolinas/farmacologia , Bases de Schiff/química , Bases de Schiff/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier
2.
Bioorg Chem ; 126: 105910, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35653899

RESUMO

The irregular use of antibiotics has created a natural selection pressure for bacteria to adapt resistance. Bacterial resistance caused by metallo-ß-lactamases (MßLs) has been the most prevalent in terms of posing a threat to human health. The New Delhi metallo-ß-lactamase-1 (NDM-1) has been shown to be capable of hydrolyzing almost all ß-lactams. In this work, eight aromatic Schiff bases 1-8 were prepared and identified by enzyme kinetic assays to be the potent inhibitors of NDM-1 (except 4). These molecules exhibited a more than 95 % inhibition, and an IC50 value in the range of 0.13-19 µM on the target enzyme, and 3 was found to be the most effective inhibitor (IC50 = 130 nM). Analysis of structure-activity relationship revealed that the o-hydroxy phenyl improved the inhibitory activity of Schiff bases on NDM-1. The inhibition mode assays including isothermal titration calorimetry (ITC) disclosed that both compounds 3 and 5 exhibited a reversibly mixed inhibition on NDM-1, with a Ki value of 1.9 and 10.8 µM, respectively. Antibacterial activity tests indicated that a dose of 64 µg·mL-1 Schiff bases resulted in 2-128-fold reduction in MICs of cefazolin on E. coli producing NDM-1 (except 4). Cytotoxicity assays showed that both Schiff bases 3 and 5 have low cytotoxicity on the mouse fibroblast (L929) cells at a concentration of up to 400 µM. Docking studies suggested that the hydroxyl group interacts with Gln123 and Glu152 of NDM-1, and the amino groups interact with the backbone amide groups of Glu152 and Asp223. This study provided a novel scaffold for the development of NDM-1 inhibitors.


Assuntos
Escherichia coli , Bases de Schiff , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Linhagem Celular , Camundongos , Testes de Sensibilidade Microbiana , Bases de Schiff/farmacologia , beta-Lactamases/química
3.
Molecules ; 27(9)2022 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-35566088

RESUMO

Chitosan (CS) and its derivatives are receiving considerable attention for their great biocompatibility and broad-spectrum activities in many fields. In this work, we aimed to characterize the antimicrobial activity of novel chitosan Schiff bases (CSSB). CS was synthesized by double deacetylation of chitin (Cn) after its extraction from the armors of crustaceans Astacus leptodactylus, and CSSB-1 and CSSB-2 were synthesized by interaction of CS with 4-(2-chloroethyl) benzaldehyde (aldehyde-1) and 4-(bromoethyl) benzaldehyde (aldehyde-2), respectively, at room temperature. The synthesized compounds were characterized by elemental analysis, gel permeation chromatography (GPC), infrared spectroscopy (FTIR), thermogravimetry (TG), and differential scanning calorimetry (DSC). The antimicrobial activity against Gram-positive (Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa) bacteria and against yeasts (Candida albicans) was significantly increased due to their higher solubility as compared to unmodified CS opening perspectives for the use of these compounds for antimicrobial prevention in different fields as, for example, food industry, cosmetics, or restoration.


Assuntos
Anti-Infecciosos , Quitosana , Aldeídos , Antibacterianos/química , Antibacterianos/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Benzaldeídos , Quitosana/química , Testes de Sensibilidade Microbiana , Bases de Schiff/química , Bases de Schiff/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier
4.
J Inorg Biochem ; 233: 111860, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35636302

RESUMO

Schiff base and its complexes are being paid more and more interests for their great prospects in biological applications. We reported here four cobalt(II) complexes [Co3(L1)2(HCOO)2] (1), [Co3(L2)2(HCOO)2(CH3OH)2]·2CH3OH (2), [Co3(HL3)2(OAc)2(DMF)2] (3) and [Co3(HL4)2(HCOO)2(DMF)2]·2H2O (4) bearing the bis-Schiff base ligand of bis(5-bromosalicylidene)-1,3-propanediamine (H2L1), bis(5-bromosalicylidene)-2-methyl-1,3-propanediamine (H2L2), bis(5-chlorosalicylidene)-2-hydroxyl-1,3-propanediamine (H3L3) and bis(5-bromosalicylidene)-2-hydroxyl-1,3-propanediamine (H3L4), respectively. The anti-tumor activities of the four titled complexes were screened on a series of tumor cell lines. After an overall consideration of their cytotoxicity on cancer cells and normal cells in comparison to those for cisplatin, complex 3 shows the best anticancer effect among the four titled complexes. It revealed the influence of anti-cancer effects of the substitution groups of H, Me and OH, as well as Cl and Br. Anticancer selectivity was also found for complex 3 on different cancer cell lines with the lowest IC50 value on T-24 cells. Complex 3 induces cell apoptosis through mitochondrial pathway as demonstrated by increasing the level of reactive oxygen species, decreasing mitochondrial membrane potential, activating caspase 3/9 and arresting cell cycle in G1 phase.


Assuntos
Complexos de Coordenação , Bases de Schiff , Cobalto , Complexos de Coordenação/farmacologia , Diaminas/farmacologia , Bases de Schiff/farmacologia
5.
Drug Des Devel Ther ; 16: 1441-1456, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35601675

RESUMO

Background: Silibinin (Sil), a flavonoid lignan-like natural compound derived from milk thistle seeds, has been used to treat hepatic diseases, including early-phase hepatocirrhosis and fatty liver, for many years. However, its poor water solubility limits its gastrointestinal absorption and bioavailability. It clinical use has been limited due to its slow onset of action. Faced with this problem, research on the derivatives of silibinin has been receiving much attention. Purpose: A series of silibinin derivatives with good biosafety and higher hepatoprotective activity were obtained by a safe, efficient and green chemical synthesis method. Patients and Methods: First, the carbonyl group in the structure of silibinin was used to obtain silibinin Schiff base derivatives by dehydration condensation with the carboxyl group in the sulfur-containing amino acid. Next, relevant experiments were performed to characterize the structure, physical form and solubility of the derivatives. Then, toxicity tests of the derivatives were performed in LO-2 cells and SD rats to evaluate their biosafety. Finally, the anti-inflammatory and antiapoptotic activities were observed using a carbon tetrachloride (CCl4)-induced acute liver injury model in C57BL/6J mice using silibinin as a control. Results: The studies showed that SS and ST behaved as amorphous substances and showed a significant increase in solubility compared to silibinin. These two derivatives showed low toxicity in biosafety tests and higher bioactivity (anti-inflammatory and anti-apoptotic) than silibinin against acute liver injury induced by CCl4. Conclusion: Two silibinin derivatives (SS and ST) obtained by the Schiff base reaction improved the solubility of the silibinin parent nucleus in biological media with the help of the hydrophilic and amorphous morphology of the ligand. The low toxicity in vivo and in vitro ensures the biosafety of the derivatives. The hepatoprotective activity (anti-inflammatory and anti-apoptotic) was significantly improved compared to silibinin.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Silimarina , Animais , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacologia , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Tetracloreto de Carbono , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Fígado , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Ratos Sprague-Dawley , Bases de Schiff/farmacologia , Silibina/farmacologia , Silimarina/química , Silimarina/farmacologia
6.
Carbohydr Polym ; 290: 119501, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35550779

RESUMO

Two imine derivatives of chitosan (i-CTs), namely 2FCT and 5MCT, were synthesized by reacting chitosan (CT) with 2-(3-formyl-1H-indol-1yl)acetonitrile (2F), and 5-methoxyindole-3-carbaldehyde (5M), respectively. The antimicrobial evaluation of i-CTs exhibited stronger inhibition effect against Staphylococcus aureus, Escherichia coli and Candida albicans. The antioxidant activity of 2FCT and 5MCT showed strong scavenging ability with IC50 2.31 and 6.92 µg/mL, respectively. The results of in vitro cytotoxicity of 2FCT and 5MCT examined using human monocyte leukemia (THP-1) cells indicate no cytotoxic effect on host cells and the value of cell viability was found to be 87.08 and 84.47%, respectively. Measurement of intracellular Reactive Oxygen Species (ROS) production by flow cytometry analysis revealed that the 2FCT and 5MCT reduced the ROS generation by 83 and 43%, respectively. In summary, these findings show that i-CTs synthesized to be promising biomaterial for biomedical applications such as wound healing.


Assuntos
Quitosana , Bases de Schiff , Antibacterianos/farmacologia , Antioxidantes/farmacologia , Quitosana/farmacologia , Escherichia coli , Humanos , Indóis , Polímeros/farmacologia , Espécies Reativas de Oxigênio/farmacologia , Bases de Schiff/farmacologia , Células THP-1
7.
Molecules ; 27(7)2022 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-35408443

RESUMO

The proton dissociation processes of two tridentate salicylidene aminoguanidine Schiff bases (SISC, Pro-SISC-Me), the solution stability and electrochemical properties of their Cu(II), Fe(II) and Fe(III) complexes were characterized using pH-potentiometry, cyclic voltammetry and UV-visible, 1H NMR and electron paramagnetic resonance spectroscopic methods. The structure of the proline derivative (Pro-SISC-Me) was determined by X-ray crystallography. The conjugation of L-proline to the simplest salicylidene aminoguanidine Schiff base (SISC) increased the water solubility due to its zwitterionic structure in a wide pH range. The formation of mono complexes with both ligands was found in the case of Cu(II) and Fe(II), while bis complexes were also formed with Fe(III). In the complexes these tridentate ligands coordinate via the phenolato O, azomethine N and the amidine N, except the complex [Fe(III)L2]+ of Pro-SISC-Me in which the (O,N) donor atoms of the proline moiety are coordinated beside the phenolato O, confirmed by single crystal X-ray crystallographic analysis. This binding mode yielded a stronger Fe(III) preference for Pro-SISC-Me over Fe(II) in comparison to SISC. This finding is also reflected in the lower redox potential value of the iron-Pro-SISC-Me complexes. The ligands alone were not cytotoxic against human colon cancer cell lines, while complexation of SISC with Cu(II) resulted in moderate activity, unlike the case of its more hydrophilic counterpart.


Assuntos
Complexos de Coordenação , Bases de Schiff , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Cristalografia por Raios X , Compostos Férricos , Compostos Ferrosos , Guanidinas , Humanos , Ligantes , Oxirredução , Prolina , Bases de Schiff/química , Bases de Schiff/farmacologia
8.
Molecules ; 27(7)2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35408596

RESUMO

Coumarin derivatives have been reported as strong antifungal agents against various phytopathogenic fungi. In this study, inhibitory effects of nine coumarinyl Schiff bases were evaluated against the plant pathogenic fungi (Fusarium oxysporum f. sp. lycopersici, Fusarium culmorum, Macrophomina phaseolina and Sclerotinia sclerotiourum). The compounds were demonstrated to be efficient antifungal agents against Macrophomina phaseolina. The results of molecular docking on the six enzymes related to the antifungal activity suggested that the tested compounds act against plant pathogenic fungi, inhibiting plant cell-wall-degrading enzymes such as endoglucanase I and pectinase. Neither compound exhibited inhibitory effects against two beneficial bacteria (Bacillus mycoides and Bradyrhizobium japonicum) and two entomopathogenic nematodes. However, compound 9 was lethal (46.25%) for nematode Heterorhabditis bacteriophora and showed an inhibitory effect against acetylcholinesterase (AChE) (31.45%), confirming the relationship between these two activities. Calculated toxicity and the pesticide-likeness study showed that compound 9 was the least lipophilic compound with the highest aquatic toxicity. A molecular docking study showed that compounds 9 and 8 bind directly to the active site of AChE. Coumarinyl Schiff bases are promising active components of plant protection products, safe for the environment, human health, and nontarget organisms.


Assuntos
Ascomicetos , Fusarium , Nematoides , Acetilcolinesterase/farmacologia , Animais , Antifúngicos/química , Antifúngicos/farmacologia , Bactérias , Fungos , Humanos , Simulação de Acoplamento Molecular , Doenças das Plantas/microbiologia , Plantas , Bases de Schiff/farmacologia , Solo
9.
Acta Chim Slov ; 69(1): 200-216, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35298011

RESUMO

The scientific interest in developing the advanced metal based compounds to inhibit and control bacterial infections is continuously rising. Keeping in view their pharmacological significance, two new bioactive symmetrical phenylenediamine mono- and bis-Schiff bases, 2-{[(4-aminophenyl)imino]methyl}-6-methoxyphenol (L1) and 2,2'-{benzene-1,2-diylbis[nitrilomethylylidene]}bis(6-methoxyphenol) (L2) have been synthesized and characterized by using physical techniques, spectral methods, elemental and DFT based computational analysis with B3LYP/6-311++G(d, p) basis set. Furthermore, the synthesized ligands were complexed with VO, Mn, Co, Ni, Cu and Zn ions in ratio [M:L,1:2 and 1:1], respectively. All the complexes exhibited significant antibacterial action against all tested bacterial strains. But overall, the zinc complexes possessed higher antibacterial activity. These results concluded that metal complexes might be promising induction in the upcoming time for medical purposes.


Assuntos
Nitrogênio , Bases de Schiff , Antibacterianos/farmacologia , Metais , Oxigênio , Bases de Schiff/farmacologia
10.
Int J Mol Sci ; 23(5)2022 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-35269699

RESUMO

Searching for adequate and effective compounds displaying antimicrobial activities, especially against Gram-positive bacteria, is an important research area due to the high hospitalization and mortality rates of these bacterial infections in both the human and veterinary fields. In this work, we explored (E)-4-amino-3-((3,5-di-tert-butyl-2-hydroxybenzylidene)amino) benzoic acid (SB-1, harboring an intramolecular hydrogen bond) and (E)-2-((4-nitrobenzilidene)amino)aniline (SB-2), two Schiff bases derivatives. Results demonstrated that SB-1 showed an antibacterial activity determined by the minimal inhibitory concentration (MIC) against Staphylococcus aureus, Enterococcus faecalis, and Bacillus cereus (Gram-positive bacteria involved in human and animal diseases such as skin infections, pneumonia, diarrheal syndrome, and urinary tract infections, among others), which was similar to that shown by the classical antibiotic chloramphenicol. By contrast, this compound showed no effect against Gram-negative bacteria (Klebsiella pneumoniae, Escherichia coli, and Salmonella enterica). Furthermore, we provide a comprehensive physicochemical and theoretical characterization of SB-1 (as well as several analyses for SB-2), including elemental analysis, ESMS, 1H and 13C NMR (assigned by 1D and 2D techniques), DEPT, UV-Vis, FTIR, and cyclic voltammetry. We also performed a computational study through the DFT theory level, including geometry optimization, TD-DFT, NBO, and global and local reactivity analyses.


Assuntos
Bactérias Gram-Positivas , Bases de Schiff , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Escherichia coli , Bactérias Gram-Negativas , Testes de Sensibilidade Microbiana , Bases de Schiff/química , Bases de Schiff/farmacologia
11.
J Med Chem ; 65(6): 5134-5148, 2022 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-35255688

RESUMO

Twelve new complexes Cu(L1)2-Cu(L12)2 were designed and synthesized to improve their chemotherapeutic properties. They showed considerable antiproliferative activity against T24 cancer cells but lower cytotoxicity to human normal cells HL-7702 and WI-38. A mechanism study indicated that Cu(L4)2 and Cu(L10)2 were reduced to Fenton-like Cu+ by glutathione depletion, and the resulting Cu+ catalyzed the generation of highly toxic hydroxyl radicals from excess H2O2. Simultaneously, Cu(L4)2 and Cu(L10)2 could decrease the catalase activity to restrain H2O2 transfer to H2O for enhanced chemodynamic therapy (CDT). These induced mitochondrial dysfunctions and endoplasmic reticulum stress to induce T24 cell apoptosis. In addition, Cu(L4)2 and Cu(L10)2 inhibited autophagy flux to promote cell apoptosis. Cu(L4)2 and Cu(L10)2 demonstrated strong tumor inhibition ability in the T24 xenograft model. Moreover, Cu(L10)2 showed higher antitumor activity and a better safety profile than the CDT agent Cu1. Cu(L10)2 exhibited excellent pharmacokinetic properties. Collectively, Cu(L4)2 and Cu(L10)2 could be developed as potential CDT candidates for cancer treatment.


Assuntos
Antineoplásicos , Hidroxiquinolinas , Neoplasias , Quinolinas , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Autofagia , Linhagem Celular Tumoral , Cobre , Glutationa , Humanos , Peróxido de Hidrogênio/farmacologia , Neoplasias/tratamento farmacológico , Bases de Schiff/farmacologia
12.
Bioorg Chem ; 122: 105708, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35290929

RESUMO

According to the World Health Organization (WHO) statistics: In 2020, there were 2.3 million women diagnosed with breast cancer and 685,000 deaths globally. Therefore, searching for new leads for fighting this type of cancer is necessary. VEGFR-2 kinase plays a crucial role in the proliferation, migration, and survival of breast cancer cells so, identifying novel inhibitors for VEGFR-2 could be effective in breast cancer treatment. Accordingly, novel heterocyclic compounds containing indole, 1,2,4-triazole, and glycosyl or allyl moieties were synthesized. The synthesized compounds were evaluated for their cytotoxic and apoptotic activities towards breast cancer cell lines (MCF7). In this regard, compounds 6, 17, and 18 exhibited promising cytotoxic activity against MCF-7 cells with IC50 values of 3.06, 1.18, and 3.02 µM compared to Sorafenib (IC50 = 2.13 µM). Interestingly, among the identified lead molecules, compound 17 displayed remarkable VEGFR2 inhibition activity with IC50 value of 19.8 nM compared to Sunitinib (IC50 = 75 nM) and Sorafenib (IC50 = 30 nM). Moreover, it is significantly stimulated apoptotic breast cancer cell death; it induced apoptosis by 17.4 %, arresting the cell cycle phases at G1 and S-phases. Additionally, in vivo (Xenograft model) study validated the anticancer activity of the hit compound 17, which showed a tumor inhibition ratio of 54.2 % compared to 5-FU (49.5%) with an improvement of hematological and biochemical parameters. The results disclosed that the identified hit compound 17 is validated for impeding cell proliferation and migration through apoptosis activation and VEGFR2 inhibition.


Assuntos
Antineoplásicos , Neoplasias da Mama , Inibidores de Proteínas Quinases , Receptor 2 de Fatores de Crescimento do Endotélio Vascular , Animais , Antineoplásicos/química , Neoplasias da Mama/patologia , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Inibidores de Proteínas Quinases/farmacologia , Bases de Schiff/farmacologia , Relação Estrutura-Atividade , Triazóis/química , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores
13.
Chem Biodivers ; 19(3): e202100686, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35137530

RESUMO

Three metal complexes [Cu(FMIMDIP)2 ] (1), [Ni(FMIMDIP)2 ] (2) and [Co(FMIMDIP)3 ] (3) where, FMIMDIP=(((furan-2-yl)methylimino)methyl)-4,6-diiodophenol, were synthesized and characterized by various spectroscopy. The analytical data revealed a square planar geometry for 1 and 2 and an octahedral geometry for 3. The kinetic and thermodynamic parameters of the thermal decomposition steps were calculated from the thermograms. The quantum chemical parameters have been calculated using HOMO-LUMO energies and reveal the stability of the complexes. The DNA interaction of 1-3 towards calf-thymus DNA was investigated by absorption titration, fluorescence spectroscopy and gel electrophoresis. All the complexes bind to DNA via intercalation mode with binding constant (Kb ) values of 4.17×103  M-1 to 5.9×104  M-1 and also effectively cleave pBR322 DNA by oxidative and photolytic techniques. The synergistic action of metal chelates with ascorbic acid induced the generation of free radicals. The antibacterial activity of 1-3 was tested against B. thuringiensis, S. pneumoniae, E. coli, and P. putida. Complex 3 has the best activity among all the complexes.


Assuntos
Complexos de Coordenação , Bases de Schiff , Antibacterianos/química , Antibacterianos/farmacologia , Antioxidantes/farmacologia , Complexos de Coordenação/química , DNA/química , Escherichia coli/metabolismo , Furanos , Ligantes , Testes de Sensibilidade Microbiana , Bases de Schiff/química , Bases de Schiff/farmacologia , Análise Espectral
14.
Int J Mol Sci ; 23(4)2022 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-35216223

RESUMO

Four novel ligand-metal complexes were synthesized through the reaction of Fe(III), pleaseCo(II), Zn(II), and Zr(IV) with Schiff base gemifloxacin reacted with ortho-phenylenediamine (GMFX-o-phdn) to investigate their biological activities. Elemental analysis, FT-IR, 1H NMR, UV-visible, molar conductance, melting points, magnetic susceptibility, and thermal analyses have been carried out for insuring the chelation process. The antimicrobial activity was carried out against Monilinia fructicola, Aspergillus flavus, Penicillium italicum, Botrytis cinerea, Escherichia coli, Bacillus cereus, Pseudomonas fluorescens, and P. aeruginosa. The radical scavenging activity (RSA%) was in vitro evaluated using ABTS method. FT-IR spectra indicated that GMFX-o-phdn chelated with metal ions as a tetradentate through oxygen of carboxylate group and nitrogen of azomethine group. The data of infrared, 1H NMR, and molar conductivity indicate that GMFX-o-phdn reacted as neutral tetra dentate ligand (N2O2) with metal ions through the two oxygen atoms of the carboxylic group (oxygen containing negative charge) and two nitrogen atoms of azomethine group (each nitrogen containing a lone pair of electrons) (the absent of peak corresponding to ν(COOH) at 1715 cm-1, the shift of azomethine group peak from 1633 cm-1 to around 1570 cm-1, the signal at 11 ppm of COOH and the presence of the chloride ions outside the complex sphere). Thermal analyses (TG-DTG/DTA) exhibited that the decaying of the metal complexes exists in three steps with the final residue metal oxide. The obtained data from DTA curves reflect that the degradation processes were exothermic or endothermic. Results showed that some of the studied complexes exhibited promising antifungal activity against most of the tested fungal pathogens, whereas they showed higher antibacterial activity against E. coli and B. cereus and low activity against P. fluorescens and P. aeruginosa. In addition, GMFX-o-phdn and its metal complexes showed strong antioxidant effect. In particular, the parent ligand and Fe(III) complex showed greater antioxidant capacity at low tested concentrations than that of other metal complexes where their IC50 were 169.7 and 164.6 µg/mL, respectively.


Assuntos
Anti-Infecciosos/farmacologia , Compostos Férricos/farmacologia , Gemifloxacina/farmacologia , Metais/farmacologia , Bases de Schiff/farmacologia , Antifúngicos/farmacologia , Bactérias/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Humanos , Ligantes , Testes de Sensibilidade Microbiana/métodos
15.
Colloids Surf B Biointerfaces ; 213: 112408, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35168105

RESUMO

Multifunctional and stimulus-sensitive intelligent nanodrug delivery systems (NDDSs) can significantly optimize the effectiveness of theranostic agents for cancer treatment. In this study, redox and pH dual-responsive nanocarriers (CPNPs) were prepared through molecular assembly by utilizing the Schiff base interactions of cystamine (Cys), PEG-NH2 and formaldehyde (FA) under aqueous conditions with a one-pot, one-step technique. First, the degradation products of CPNPs exhibited good biocompatibility, and the high concentration of intact CPNPs (200 µg/mL) could inhibit the growth of cells. In addition, doxorubicin (DOX) was encapsulated in CPNPs simply by changing the pH (DOX@CPNPs), and pH/GSH-responsive release behaviour was confirmed. In vitro, CPNPs significantly increased the uptake of DOX and enhanced the cytotoxicity of DOX to tumour cells. More importantly, DOX@CPNPs strongly reversed drug resistance in three different types of cancer cells, exhibiting significant anticancer effects. Collectively, this study presents the easy preparation of nanomedicines that respond to multiple stimuli, which highlights the advantages of Schiff base-based nanomedicines for cancer therapy and reversing chemoresistance.


Assuntos
Neoplasias , Polietilenoglicóis , Doxorrubicina/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Resistencia a Medicamentos Antineoplásicos , Humanos , Concentração de Íons de Hidrogênio , Neoplasias/tratamento farmacológico , Polietilenoglicóis/química , Bases de Schiff/farmacologia
16.
Carbohydr Polym ; 278: 118970, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-34973785

RESUMO

In this study, to investigate the influence of glyoxylate bearing Schiff base on bioactivity to chitosan quaternary ammonium salts, different chitosan derivatives were synthesized by ion exchange of glyoxylate bearing Schiff base with chitosan quaternary ammonium salts (TMCI and HACC). For this purpose, glyoxylate was prepared by Schiff base reaction of glyoxylic acid and amino heterocycles and it was further ionization to substitute iodide ions and chloride ions. After structural characterization by FTIR and 1H NMR, the antifungal and antioxidant activities were measured. Results indicated that glyoxylate bearing Schiff base could improve the bioactivity of TMCI and HACC obviously. Specifically, anionic TMCI with Schiff base of amino pyridines possessed best antioxidant activity >92.40% at 1.6 mg/mL against DPPH radicals. Meanwhile, they showed antifungal activity >84.88% at 1.0 mg/mL against G. cingulate. Furthermore, the cytotoxicity was evaluated, and all samples showed good cell viability >80.14% at 1000 µg/mL.


Assuntos
Antifúngicos/farmacologia , Antioxidantes/farmacologia , Quitosana/farmacologia , Fungos/efeitos dos fármacos , Glioxilatos/farmacologia , Compostos de Amônio Quaternário/farmacologia , Antifúngicos/síntese química , Antifúngicos/química , Antioxidantes/síntese química , Antioxidantes/química , Compostos de Bifenilo/antagonistas & inibidores , Quitosana/química , Glioxilatos/química , Testes de Sensibilidade Microbiana , Picratos/antagonistas & inibidores , Compostos de Amônio Quaternário/química , Bases de Schiff/química , Bases de Schiff/farmacologia
17.
Arch Pharm (Weinheim) ; 355(4): e2100430, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34994010

RESUMO

In this study, a series of novel Schiff base derivatives containing a pyrazolone ring (2a-e) were designed, successfully synthesized for the first time, and characterized by elemental analysis and some spectroscopic methods. These compounds were tested for their inhibitory activities on acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and the human carbonic anhydrase isoenzymes I and II (hCA I and II). All synthesized molecules indicated significant inhibition effects with IC50 values ranging from 14.15 to 107.62 nM against these enzymes. Compound 2d showed the most potent inhibitory activity among the tested molecules toward AChE and BChE (IC50 = 15.07 and 14.15 nM) compared to the standard drug neostigmine. We determined that the IC50 values of the tested molecules ranged between 16.86 and 57.96 nM for hCA I and 15.24-46.21 nM for hCA II. As a consequence, we may say that some of the Schiff base derivatives may be used as potential drug candidates in later studies.


Assuntos
Acetilcolinesterase , Butirilcolinesterase , Acetilcolinesterase/metabolismo , Butirilcolinesterase/metabolismo , Inibidores da Anidrase Carbônica , Inibidores da Colinesterase/química , Inibidores Enzimáticos/farmacologia , Humanos , Estrutura Molecular , Bases de Schiff/farmacologia , Relação Estrutura-Atividade
18.
Bioorg Chem ; 119: 105507, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34836646

RESUMO

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.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Complexos de Coordenação/farmacologia , Desenho de Fármacos , Antibacterianos/síntese química , Antibacterianos/química , Antifúngicos/síntese química , Antifúngicos/química , Candida albicans/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Relação Dose-Resposta a Droga , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Processos Fotoquímicos , Bases de Schiff/síntese química , Bases de Schiff/química , Bases de Schiff/farmacologia , Relação Estrutura-Atividade
19.
Chem Biol Interact ; 351: 109714, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34710376

RESUMO

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.


Assuntos
Antibacterianos/farmacologia , Complexos de Coordenação/farmacologia , Bases de Schiff/farmacologia , Tripanossomicidas/farmacologia , Amicacina/farmacologia , Animais , Antibacterianos/química , Artemia/efeitos dos fármacos , Complexos de Coordenação/química , Sinergismo Farmacológico , Escherichia coli/efeitos dos fármacos , Gentamicinas/farmacologia , Leishmania infantum/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Níquel/química , Testes de Sensibilidade Parasitária , Pseudomonas aeruginosa/efeitos dos fármacos , Bases de Schiff/química , Staphylococcus aureus/efeitos dos fármacos , Tripanossomicidas/química
20.
J Biol Inorg Chem ; 27(1): 89-109, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34817681

RESUMO

We report the synthesis, characterization and biological screening of new chromone Schiff bases derived from the condensation of three 6-substituted-3-formyl-chromones with pyridoxal (HL1-3) and its Cu(II) complexes [Cu(L1-3)Cl], 1-3. For the 6-methyl derivative, HL2, the VIVO-complex [VO(L2)Cl] (5), as well as ternary Cu and VIVO complexes with 1,10-phenanthroline (phen), [Cu(L2)(phen)Cl] (4) and [VO(L2)(phen)Cl] (6), were also prepared and evaluated. Their stability in aqueous medium and radical scavenging activity toward DPPH are screened, with [Cu(L2)(phen)Cl] (4) showing hydrolytic stability and [VO(L2)(phen)Cl] (6) high radical scavenging activity. Spectroscopic studies establish bovine serum albumin (BSA), a model for HSA, as a potential reversible carrier of [Cu(L2)(phen)Cl] in blood with KBC ≈ 105 M-1. The cytotoxic activity of a group of compounds is evaluated against a panel of human cancer cell lines of different origin (ovary, cervix, brain and breast) and compared to normal cells. Our results indicate that Cu complexes are more cytotoxic than the ligands but not selective towards cancer cells. The most potent complexes (4 and 6) are further evaluated for their apoptotic potential, induction of reactive oxygen species (ROS) and genotoxicity. Both complexes efficiently triggered cell death through apoptosis as evaluated by DNA morphology and TUNEL assay, increased ROS formation as determined by DCFDA (2',7'-dichlorodihydrofluorescein diacetate) analysis, and induced genotoxic damage as visualized via COMET assay in all cancer cells under study. Therefore, 4 and 6 may be potential precursor anticancer molecules, yet they need to be targeted toward cancer cells.


Assuntos
Antineoplásicos , Complexos de Coordenação , Antineoplásicos/química , Cromonas/farmacologia , Complexos de Coordenação/química , Cobre/química , Humanos , Fenantrolinas/química , Bases de Schiff/química , Bases de Schiff/farmacologia
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