RESUMO
Although the crystals of coordination polymer {[CuCl(µ-O,O'-L-Br2Tyr)]}n (1) (L-Br2Tyr = 3,5-dibromo-L-tyrosine) were formed under basic conditions, crystallographic studies revealed that the OH group of the ligand remained protonated. Two adjacent [CuCl(L-Br2Tyr)] monomers, bridged by the carboxylate group of the ligand in the syn-anti bidentate bridging mode, are differently oriented to form a polymeric chain; this specific bridging was detected also by FT-IR and EPR spectroscopy. Each Cu(II) ion in polymeric compound 1 is coordinated in the xy plane by the amino nitrogen and carboxyl oxygen of the parent ligand and the oxygen of the carboxyl group from the symmetry related ligand of the adjacent [Cu(L-Br2Tyr)Cl] monomer, as well as an independent chlorine ion. In addition, the Cu(II) ion in the polymer chain participates in long-distance intermolecular contacts with the oxygen and bromine atoms of the ligands located in the adjacent chains; these intramolecular contacts were also supported by NCI and NBO quantum chemical calculations and Hirshfeld surface analysis. The resulting elongated octahedral geometry based on the [CuCl(L-Br2Tyr)] monomer has a lower than axial symmetry, which is also reflected in the symmetry of the calculated molecular EPR g tensor. Consequently, the components of the d-d band obtained by analysis of the NIR-VIS-UV spectrum were assigned to the corresponding electronic transitions.
RESUMO
A new ZnII coordination polymer (CP) based on 2,3-pyrazine dicarboxylic acid (H2pzdc) and 4,4'-bipyridine (bpy) (ZCP) was synthesized using a facile slow evaporation method. Single-crystal X-ray diffraction revealed that ZCP is a two-dimensional porous CP, [Zn2(pzdc)2(bpy)(H2O)2]n, with van der Waals forces as the dominant interaction within its layers forming a 63 network. Employing energetic ultrasound irradiation, nanoscale ZCP (nZCP) was successfully synthesized and Eu3+ ions were incorporated within its host lattice (Eu@nZCP). The resulting platform exhibits superior fluorescence characteristics and demonstrates notable optical durability. Therefore, it was used as a dual detection fluorescent sensing platform for the detection of mercury and L-cysteine (L-Cys) in aqueous media through a turn-off/on strategy. In the turn-off process, the fluorescence emission of Eu@nZCP progressively quenches by the addition of HgII via a photo-induced electron transfer (PET) mechanism. The fluorescence of Eu@nZCP is quenched to establish a low fluorescence background through the incorporation of HgII. This devised turn-on fluorescent system is suitable for the recognition of L-Cys (based on the strong affinity of L-Cys to the HgII ion) through a quencher detachment mechanism. This method attained a relatively wide linear range, spanning from 0.001 to 25â µM, with the low detection limit of 5 nM for the sensing of HgII. Also, the corresponding limit of detection (LOD) for L-Cys is 8â nM in a relatively wide linear range, spanning from 0.001 to 40â µM.
RESUMO
Combretastatins isolated from the Combretum caffrum tree belong to a group of closely related stilbenes. They are colchicine binding site inhibitors which disrupt the polymerization process of microtubules in tubulins, causing mitotic arrest. In vitro and in vivo studies have proven that some combretastatins exhibit antitumor properties, and among them, combretastatin A-4 is the most active mitotic inhibitor. In this study, a series of novel combretastatin A-4 analogs containing carboxylic acid, ester, and amide moieties were synthesized and their cytotoxic activity against six tumor cell lines was determined using sulforhodamine B assay. For the most cytotoxic compounds (8 and 20), further studies were performed. These compounds were shown to induce G0/G1 cell cycle arrest in MDA and A549 cells, in a concentration-dependent manner. Moreover, in vitro tubulin polymerization assays showed that both compounds are tubulin polymerization enhancers. Additionally, computational analysis of the binding modes and binding energies of the compounds with respect to the key human tubulin isotypes was performed. We have obtained a satisfactory correlation of the binding energies with the IC50 values when weighted averages of the binding energies accounting for the abundance of tubulin isotypes in specific cancer cell lines were computed.
Assuntos
Proliferação de Células , Desenho de Fármacos , Estilbenos , Moduladores de Tubulina , Tubulina (Proteína) , Humanos , Tubulina (Proteína)/metabolismo , Tubulina (Proteína)/química , Proliferação de Células/efeitos dos fármacos , Moduladores de Tubulina/farmacologia , Moduladores de Tubulina/síntese química , Moduladores de Tubulina/química , Estilbenos/farmacologia , Estilbenos/química , Estilbenos/síntese química , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Relação Estrutura-Atividade , Simulação de Acoplamento Molecular , Células A549 , Polimerização/efeitos dos fármacos , Ensaios de Seleção de Medicamentos AntitumoraisRESUMO
A new organic-functionalized Cu-based Anderson-type polyoxomolybdate, namely (C7H15N4)2[Na(H2O)4]2[C6H12CuMo6N2O24]·2(H2O) (CuII-POM), was synthesized via a simple one-pot reaction and subsequently characterized using a range of analytical and spectral techniques. Structural investigation by single crystal X-ray diffraction analysis revealed that the polyanion component of the synthesized compound (i.e. [C6H12CuMo6N2O24]4-) possesses a δ-isomer Anderson-type structure, which is surrounded by four lattice water molecules and four [C7H15N4-NaH15(H2O)8]4+ cations in the crystal packing arrangement. The resulting double-sided tris-functionalized Anderson-type compound can function as highly effective heterogeneous photocatalysts for the copper(I)-catalyzed Huisgen azide-alkyne cycloaddition (Cu-AAC) reaction of terminal alkyne, benzyl halides, and sodium azide (acts as the azidonation and reducing agent) in aqueous media. Ultraviolet light irradiation enhances the catalytic activity of CuII-POM ~ 4.4 times of the "off" situation under reaction conditions of 0.00239 mmol cat., 80 °C, 8 h, 2 mL H2O, So that the isolated yields for the AAC reaction involving a variety of terminal alkynes and benzyl halides using the CuII-POM catalyst ranged between 19-97%. The current study is the first report about using an efficient and economical Cu(II)-POM/UV/NaN3 catalytic system in the Cu-AAC reaction and reveals its significant potential for applying to other Cu(I)-catalyzed reactions.
RESUMO
Colchicine shows very high antimitotic activity, therefore, it is used as a lead compound for generation of new anticancer agents. In the hope of developing novel, useful drugs with more favourable pharmacological profiles, a series of doubly modified colchicine derivatives has been designed, synthesized and characterized. These novel carbamate or thiocarbamate derivatives of 10-demethoxy-10-methylaminocolchicine have been tested for their antiproliferative activity against four human cancer cell lines. Additionally, their mode of action has been evaluated as colchicine binding site inhibitors, using molecular docking studies. Most of the tested compounds showed greater cytotoxicity (IC50 in a low nanomolar range) and were characterized by a higher selectivity index than standard chemotherapeutics such as cisplatin and doxorubicin as well as unmodified colchicine. Their pharmacological use in cancer therapy could possibly be accomplished with lower dosages and result in less acute toxicity problems than in the case of colchicine. In addition, we present a QSAR model for predicting the antiproliferative activity of doubly modified derivatives for two tumour cell lines.
Assuntos
Antineoplásicos/farmacologia , Colchicina/análogos & derivados , Colchicina/farmacologia , Tiocarbamatos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Colchicina/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Ligação Proteica , Relação Quantitativa Estrutura-Atividade , Tiocarbamatos/síntese química , Tiocarbamatos/metabolismo , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/síntese química , Moduladores de Tubulina/metabolismo , Moduladores de Tubulina/farmacologiaRESUMO
This scenario was designed to investigate the protein corona pattern on the pillar-layer surface of a Cu-based metal-organic framework (MOF) in human plasma. The [Cu(L)(L/)].1.3DMA (MOF-1) {L = 4, 4/-bipyridine and L/ = 5-aminoisophthalic acid}, was synthesized through the sonochemical irradiation approach as well as characterized by various techniques like scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray powder diffraction and single-crystal X-ray diffraction. The space group was determined to be an orthorhombic space group (Pbam) by single-crystal X-ray diffraction. Single-crystal X-ray analyses on MOF-1 showed that Cu+2 ion was 6-coordinated. Besides, to study and clarify interactions between MOFs and biological milieu, human whole blood plasma was selected as a model. Fluorescence spectroscopy and SDS-PAGE techniques were employed to explore quantitative and qualitative in situ characterization of protein corona as well. Furthermore, cell viability in a cancerous cell lines was evaluated by MTT assay in the presence and absence of the corona. The results from SDS-PAGE illustrated that the most adsorbed quantity among plasma proteins belongs to fibrinogen (α, ß and γ chains), and this protein showed the maximum frequency on the MOF-1s surface, so the possible interactions of MOF-1s with fibrinogen also studied using fluorescence spectroscopy and corresponding data were plotted. According to the obtained data from MTT assay, these structures have concentration-dependent toxicity. In brief, based on the obtained data in the current study, the designed MOF can be introduced as a new desirable carrier for drug/gen delivery after further prerequisite assessments.
Assuntos
Neoplasias da Mama/patologia , Proliferação de Células , Estruturas Metalorgânicas/farmacologia , Coroa de Proteína/química , Albumina Sérica Humana/farmacologia , Soroglobulinas/farmacologia , Neoplasias da Mama/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Feminino , Humanos , Células MCF-7 , Estruturas Metalorgânicas/químicaRESUMO
Due to the inherent geometrical interdependencies of nucleic acid structures, the ability to engineer biosensors that rely on the specific interactions of these compounds is of considerable importance. Additionally, sensing or screening in a label-free fashion is a capability of these structures that can be readily achieved by exploiting the fluorescent component. In this work, the [AdH]6[V10O28].4(H2O) (1) supramolecular structure is introduced using adenine and decavanadate moieties that allow probing of selectivity to specific nucleic acid binding events by optical changes. The structure of (1) is an alternating organic-inorganic hybrid architecture of cationic adeninium (AdH+) ribbons and anionic decavanadate (DV)-water sheets. The luminescent screening and anticancer activity of compound (1) on the two human mammary carcinoma cell lines MDA-MB-231 and MCF7 were investigated using fluorescent microscopy and MTT assays, respectively. It was found that compound (1) is cell permeable with no toxicity below 12.5â µM concentration and moderate cytotoxicity at concentrations as high as 200â µM in human breast cancer cell lines, making it a useful tool to study the cell nucleus in real time.
Assuntos
Adenina/química , Vanadatos/química , Vanádio/farmacologia , Adenina/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Humanos , Substâncias Macromoleculares/síntese química , Substâncias Macromoleculares/química , Substâncias Macromoleculares/farmacologia , Microscopia de Fluorescência , Modelos Moleculares , Vanadatos/farmacologia , Vanádio/química , Água/químicaRESUMO
Colchicine is a well-known compound with strong antiproliferative activity that has had limited use in chemotherapy because of its toxicity. In order to create more potent anticancer agents, a series of novel colchicine derivatives have been obtained by simultaneous modification at C7 (amides and sulfonamides) and at C10 (methylamino group) positions and characterized by spectroscopic methods. All the synthesized compounds have been tested in vitro to evaluate their cytotoxicity toward A549, MCF-7, LoVo, LoVo/DX and BALB/3T3 cell lines. Additionally, the activity of the studied compounds was investigated using computational methods involving molecular docking of the colchicine derivatives to ß-tubulin. The majority of the obtained derivatives exhibited higher cytotoxicity than colchicine, doxorubicin or cisplatin against tested cancer cell lines. Furthermore, molecular modeling studies of the obtained compounds revealed their possible binding modes into the colchicine binding site of tubulin.
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Técnicas de Química Sintética , Colchicina/análogos & derivados , Modelos Moleculares , Sulfonamidas/química , Sulfonamidas/farmacologia , Antineoplásicos/síntese química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Colchicina/síntese química , Colchicina/química , Colchicina/farmacologia , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Estrutura Molecular , Eletricidade Estática , Relação Estrutura-Atividade , Sulfonamidas/síntese químicaRESUMO
As a group of biologically active compounds, polyether antibiotics (ionophores) show a broad spectrum of interesting pharmacological properties, ranging from anti-bacterial to anti-cancer activities. There is increasing evidence that ionophores, including salinomycin (SAL), and their semi-synthetic analogues are promising candidates for the development of drugs against parasitic diseases. Our previous studies have shown that esterification and amidation of the C1 carboxylate moiety of SAL provides compounds with potent activity against Trypanosoma brucei, protozoan parasites responsible for African trypanosomiasis. In this paper, we present the synthetic pathways, crystal structures and anti-trypanosomal activity of C1 esters, amides and hydroxamic acid conjugates of SAL, its C20-oxo and propargylamine analogues as well novel C1/C20 doubly modified derivatives. Evaluation of the trypanocidal and cytotoxic activity using bloodstream forms of T. brucei and human myeloid HL-60â¯cells revealed that the single-modified C20-oxo and propargylamine precursor molecules 10 and 16 were the most anti-trypanosomal and selective compounds with 50% growth inhibition (GI50) values of 0.037 and 0.035⯵M, and selectivity indices of 252 and 300, respectively. Also the salicylhydroxamic acid conjugate of SAL (compound 9) as well as benzhydroxamic acid and salicylhydroxamic acid conjugates of 10 (compounds 11 and 12) showed promising trypanocidal activities with GI50 values between 0.032 and 0.035⯵M but less favorable selectivities. The findings confirm that modification of SAL can result in derivatives with improved trypanocidal activity that might be interesting lead compounds for further anti-trypanosomal drug development.
Assuntos
Ácidos Hidroxâmicos/farmacologia , Salicilamidas/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma brucei brucei/efeitos dos fármacos , Tripanossomíase Africana/tratamento farmacológico , Sobrevivência Celular/efeitos dos fármacos , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Células HL-60 , Humanos , Ácidos Hidroxâmicos/síntese química , Ácidos Hidroxâmicos/química , Modelos Moleculares , Estrutura Molecular , Testes de Sensibilidade Parasitária , Salicilamidas/síntese química , Salicilamidas/química , Relação Estrutura-Atividade , Tripanossomicidas/síntese química , Tripanossomicidas/química , Células Tumorais CultivadasRESUMO
Two nickel(II) complexes with substituted bipyridine ligand of the type [Ni(NN)3](ClO4)2, where NN is 4,4'-dimethyl-2,2'-bipyridine (dimethylbpy) (1) and 4,4'-dimethoxy-2,2'-bipyridine (dimethoxybpy) (2), have been synthesized, characterized, and their interaction with DNA and bovine serum albumin (BSA) studied by different physical methods. X-ray crystal structure of 1 shows a six-coordinate complex in a distorted octahedral geometry. DNA-binding studies of 1 and 2 reveal that both complexes sit in DNA groove and then interact with neighboring nucleotides differently; 2 undergoes a partial intercalation. This is supported by molecular-docking studies, where hydrophobic interactions are apparent between 1 and DNA as compared to hydrogen bonding, hydrophobic, and π-π interactions between 2 and DNA minor groove. Moreover, the two complexes exhibit oxidative cleavage of supercoiled plasmid DNA in the presence of hydrogen peroxide as an activator in the order of 1 > 2. In terms of interaction with BSA, the results of spectroscopic methods and molecular docking show that 1 binds with BSA only via hydrophobic contacts while 2 interacts through hydrophobic and hydrogen bonding. It has been extensively demonstrated that the nature of the methyl- and methoxy-groups in ligands is a strong determinant of the bioactivity of nickel(II) complexes. This may justify the above differences in biomolecular interactions. In addition, the in vitro cytotoxicity of the complexes on human carcinoma cells lines (MCF-7, HT-29, and U-87) has been examined by MTT assay. According to our observations, 1 and 2 display cytotoxicity activity against selected cell lines. Communicated by Ramaswamy H. Sarma.
Assuntos
Antineoplásicos/química , Bicarbonatos/química , Complexos de Coordenação/química , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Níquel/química , Piridinas/química , Trometamina/química , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/farmacologia , DNA/química , Clivagem do DNA , Estabilidade de Medicamentos , Humanos , Estrutura Molecular , Soroalbumina Bovina/química , Análise EspectralRESUMO
Designable coordination polymers with suitable chemical diversities and biocompatible structures have been proposed as a promising class of vehicles for drug delivery systems. Here, we hydrothermally synthesized a novel one-dimensional (1D) coordination polymer, [Zn(H2O)6K2(H2BTC)2(H2O)4](H2BTC)2·2H2O, where H3BTC = benzene-1,3,5-tricarboxylic acid (trimesic acid), cp.1. As the hydrogen bonds stabilized 1D chains in three dimensions, the cp.1 could be a good candidate for delivering small-molecule chemotherapeutics such as 5-fluorouracil (5-Fu). The synthesized cp.1 showed a remarkable 5-Fu loading of 66% with encapsulation efficiency of 98% and almost complete release process. The 5-Fu-loaded cp.1 displayed a time-dependent cytotoxicity effect against breast cancer cell lines MCF-7 and 4T1. The cellular uptake of cp.1 particles was investigated via confocal laser scanning microscopy using fluorescein isothiocyanate and LysoTracker Red staining. Furthermore, the in vivo antitumor impact of 5-Fu-loaded cp.1 was studied on 4T1 breast cancer BALB/c mice model. The intratumor treatment of 5-Fu-loaded cp.1 demonstrated beneficial antitumor efficacy by postponing tumor growth. These results suggest that the 5-Fu-loaded cp.1 microparticles with a great locoregional delivery can be efficient anticancer drug carriers for further clinical treatments.
Assuntos
Neoplasias da Mama , Animais , Linhagem Celular Tumoral , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Fluoruracila , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas , PolímerosRESUMO
In order to create more potent anticancer agents, a series of five structurally different derivatives of Colchicine have been synthesised. These compounds were characterised spectroscopically and structurally and their antiproliferative activity against four human tumour cell lines (HL-60, HL-60/vinc, LoVo, LoVo/DX) was evaluated. Additionally the activity of the studied compounds was calculated using computational methods involving molecular docking of the Colchicine derivatives to ß-tubulin. The experimental and computational results are in very good agreement indicating that the antimitotic activity of Colchicine derivatives can be readily predicted using computational modeling methods.
Assuntos
Antineoplásicos/farmacologia , Colchicina/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Sítios de Ligação , Linhagem Celular Tumoral , Colchicina/síntese química , Colchicina/química , Humanos , Simulação de Acoplamento Molecular , Tubulina (Proteína)/químicaRESUMO
Three zinc(II) ions in combination with two units of enantiopure [3+3] triphenolic Schiff-base macrocycles 1, 2, 3, or 4 form cage-like chiral complexes. The formation of these complexes is accompanied by the enantioselective self-recognition of chiral macrocyclic units. The X-ray crystal structures of these trinuclear complexes show hollow metal-organic molecules. In some crystal forms, these barrel-shaped complexes are arranged in a window-to-window fashion, which results in the formation of 1D channels and a combination of both intrinsic and extrinsic porosity. The microporous nature of the [Zn3 12 ] complex is reflected in its N2 , Ar, H2 , and CO2 adsorption properties. The N2 and Ar adsorption isotherms show pressure-gating behavior, which is without precedent for any noncovalent porous material. A comparison of the structures of the [Zn3 12 ] and [Zn3 32 ] complexes with that of the free macrocycle H3 1 reveals a striking structural similarity. In H3 1, two macrocyclic units are stitched together by hydrogen bonds to form a cage very similar to that formed by two macrocyclic units stitched together by Zn(II) ions. This structural similarity is manifested also by the gas adsorption properties of the free H3 1 macrocycle. Recrystallization of [Zn3 12 ] in the presence of racemic 2-butanol resulted in the enantioselective binding of (S)-2-butanol inside the cage through the coordination to one of the Zn(II) ions.
RESUMO
As part of our program to develop anticancer agents, we have synthesized new compounds, which are conjugates between well-known anticancer drug, floxuridine and salinomycin which is able to selectivity kill cancer stem cells. The conjugates were obtained in two ways i.e. by copper(I) catalysed click Huisgen cycloaddition reaction performed between 3'-azido-2',3'-dideoxy-5-fluorouridine and salinomycin propargyl amide, and by the ester synthesis starting from salinomycin and floxuridine under mild condition. The compounds obtained were characterized by spectroscopic methods and evaluated for their in vitro cytotoxicity against seven human cancer cell lines as well as antibacterial activity against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE). The conjugate obtained by esterification reaction showed a significantly higher antiproliferative activity against the drug-resistant cancer cells and lower toxicity than those of salinomycin and floxuridine towards normal cells, as well as standard anticancer drugs, such as cisplatin and doxorubicin. The conjugate compound revealed also moderate activity against MRSA and MRSE bacterial strains. Very high activity of floxuridine and 5-fluorouracil against MRSA and MRSE has been also observed.
Assuntos
Antibacterianos/síntese química , Antineoplásicos/síntese química , Floxuridina/química , Piranos/química , Antibacterianos/química , Antibacterianos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Desenho de Fármacos , Floxuridina/farmacologia , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Estrutura Molecular , Piranos/farmacologia , Staphylococcus epidermidis/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
A series of 12 novel monosubstituted N-benzyl amides of salinomycin (SAL) was synthesized for the first time and characterized by NMR and FT-IR spectroscopic methods. Molecular structures of three salinomycin derivatives in the solid state were determined using single crystal X-ray method. All compounds obtained were screened for their antiproliferative activity against various human cancer cell lines as well as against the most problematic bacteria strains such as methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE), and Mycobacterium tuberculosis. Novel salinomycin derivatives exhibited potent anticancer activity against drug-resistant cell lines. Additionally, two N-benzyl amides of salinomycin revealed interesting antibacterial activity. The most active were N-benzyl amides of SAL substituted at -ortho position and the least anticancer active derivatives were those substituted at the -para position.
Assuntos
Amidas/síntese química , Amidas/farmacologia , Antibacterianos/síntese química , Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Piranos/síntese química , Piranos/farmacologia , Amidas/química , Antibacterianos/química , Antineoplásicos/síntese química , Antineoplásicos/química , Antituberculosos/farmacologia , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Linhagem Celular Tumoral , Cristalografia por Raios X , Humanos , Ligação de Hidrogênio , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/efeitos dos fármacos , Espectroscopia de Prótons por Ressonância Magnética , Piranos/química , Espectrometria de Massas por Ionização por Electrospray , Espectroscopia de Infravermelho com Transformada de Fourier , Staphylococcus epidermidis/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
A series of 12 novel ester derivatives of naturally occurring polyether antibiotic - salinomycin were synthesized, characterised by spectroscopic method and evaluated for their in vitro antibacterial activity and cytotoxicity. The new esters were demonstrated to form complexes with monovalent and divalent metal cation of 1:1 stoichiometry in contrast to the salinomycin which forms only complexes with monovalent cations. All the obtained compounds show potent antiproliferative activity against human cancer cell lines and a good selectivity index for cancer versus mammalian cells. Additionally, 3 compounds showed higher antiproliferative activity against the drug-resistant cancer cells and lower toxicity towards normal cells than those of unmodified salinomycin and standard anticancer drugs such as cisplatin and doxorubicin. Some of the synthesized compounds showed good inhibitory activity against Staphylococcus strains and clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE). These studies show that salinomycin esters are interesting scaffolds for the development of novel anticancer and Gram-positive antibacterial agents.
Assuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Piranos/síntese química , Piranos/farmacologia , Antibacterianos/química , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Ésteres/química , Humanos , Espectroscopia de Ressonância Magnética , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Modelos Moleculares , Piranos/química , Staphylococcus epidermidis/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
A series of 11 novel amides of salinomycin were synthesized for the first time. All the obtained compounds were found to show potent antiproliferative activity against human cancer cell lines including the drug-resistant cancer cells. Four new salinomycin derivatives revealed good antibacterial activity against clinical isolates of methicillin-resistant Staphylococcus epidermidis (MRSE).
Assuntos
Amidas/farmacologia , Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Bactérias/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Piranos/farmacologia , Amidas/síntese química , Amidas/química , Animais , Antibacterianos/síntese química , Antibacterianos/química , Antineoplásicos/síntese química , Antineoplásicos/química , Células 3T3 BALB , Bactérias/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Fibroblastos/citologia , Células HL-60 , Humanos , Camundongos , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Molecular , Piranos/síntese química , Piranos/química , Relação Estrutura-AtividadeRESUMO
Antiproliferative activity of seven amides and one benzotriazole ester derivative of salinomycin, a polyether ionophore antibiotic, with recently reported antibacterial activity, are herein described. Salinomycin and the majority of derivatives exhibit potent antiproliferative activity against the drug-resistant cancer cell lines. Moreover almost all derivatives show stronger activity against LoVo/DX cell line than that of unmodified salinomycin.
Assuntos
Antineoplásicos/química , Piranos/química , Amidas/química , Antineoplásicos/síntese química , Antineoplásicos/toxicidade , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cristalografia por Raios X , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Células HL-60 , Humanos , Conformação Molecular , Piranos/síntese química , Piranos/toxicidade , Relação Estrutura-Atividade , Triazóis/químicaRESUMO
The title manganese(III) phthalocyaninate (Pc) complex, viz. iodo[phthalocyaninato(2-)]manganese(III) hemi(diiodine), [Mn(C32H16N8)I].0.5I2 or (MnPcI)2.I2, was obtained from the reaction of pure powdered manganese with phthalonitrile under oxidation conditions of iodine vapour. The phthalocyaninato(2-) residue is not strictly planar and the Mn atom is five-coordinate, having distorted square-pyramidal geometry and residing 0.262 (2) A above the plane defined by the four isoindole N atoms of the phthalocyaninate macrocycle. The neutral I2 molecule bridges the iodo[phthalocyaninato(2-)]manganese(III) molecules, forming a centrosymmetric dimeric structure.
RESUMO
Crystals of diiodo[phthalocyaninato(1-)] chromate(III) diiodine, CrPcI(2).I(2), were grown directly in the reaction of chromium powder with 1,2-dicyanobenzene under a stream of iodine at about 250 degrees C. The CrPcI(2).I(2) complex crystallizes in the centrosymmetric space group of the triclinic system with one molecule per unit cell, with the cell dimensions a = 7.851(2) A, b = 8.402(2) A, c = 12.668(3) A, alpha = 80.32(3)(o), beta = 74.06(3)(o), gamma = 82.33(3)(o), and V = 788.7(3) A(3). The X-ray single-crystal analysis shows that each of the centrosymmetric CrPcI(2) molecules is bridged by a neutral I(2) molecule (detected also by Raman spectroscopy) and develops a polymeric one-dimensional structure. The magnetic measurements have been carried out in the temperature range 300-2 K. Temperature dependence of the effective magnetic moment, mu(eff), shows the ferro- and antiferromagnetic interactions in the system of the paramagnetic central Cr(3+) ion and surrounding pi-conjugated radical ligand Pc(1-). The conductivity measurement on a polycrystalline sample exhibits weak temperature dependence (dsigma/dT < 0). The UV-vis spectrum exhibits, besides the B- and Q-bands, one additional band assigned to the electronic transition from a deeper level to the half-occupied HOMO level in the one-electron oxidized phthalocyaninato(1-) radical ligand.