A novel fluorescent ligand (H2LCl⋅1.5CH3OH, 1) was synthesized and metal complexes of 1 with Mn(II), Fe(III), Ni(II), Cu(II), and Zn(II) were obtained as Mn(HL)2Cl2 (2), Fe(HL)2Cl3⋅3H2O (3), Ni(L)(HL)Cl⋅8H2O (4), Cu(HL)Cl2⋅4H2O (5), Zn(H2L)Cl3 (6), respectively. These compounds were identified by spectroscopic methods, elemental analysis, molar conductivity, and single-crystal X-ray crystallography. According to the crystal structure of 4 nickel (II), center is surrounded by two ligands in a distorted octahedral geometry. The ligand and its complexes are soluble in water and have excellent stability. In vitro anti-proliferative activity of these compounds was evaluated against human breast adenocarcinoma (MCF-7) and human lipo-sarcoma (SW-872) as cancer cells and human fibroblasts (HFF-2) as normal cells by MTT assay. Interestingly, complex 5 exhibited excellent activity against both cancer cells with low IC50 value 22.18 ± 0.35 μg/mL (35.66 ± 0.56 μM) for SW-872 and 79.41 ± 3.54 μg/mL (127.6 ± 5.69 μM) for MCF-7 among the compounds and in comparison with paclitaxel (PTX) which acts finely. Morphological changes were evaluated by flow cytometry that revealed apoptosis is the main cause of cell death. Likewise, cell cycle studies indicated the cell cycle arrest in the G1 and S phases for complex 5 against MCF-7 and SW-872 cancer cells, while complex 6 could arrest the MCF-7 and SW-872 cells in G2 and G1 phases, respectively. All of the compounds are fluorescent which enabled us to monitor the uptake and intracellular distribution in living human cancer cells by fluorescence microscopy.
- MeSH
- komplexní sloučeniny * farmakologie chemie MeSH
- lidé MeSH
- ligandy MeSH
- měď chemie MeSH
- protinádorové látky * farmakologie chemie MeSH
- Schiffovy báze farmakologie chemie MeSH
- thiosemikarbazony * chemie MeSH
- železité sloučeniny MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
A mononuclear cadmium(II) complex of formula [Cd(5,5'-dmbipy)2(OAc)2]·2H2O (5,5'-dmbipy = 5,5'-dimethyl-2,2'-bipyridine and OAc = acetato ligand) has been synthesized and characterized by FT-IR, UV-Vis, 1H-NMR, elemental analysis and single-crystal X-ray structure analysis. The molecular structure of the complex shows a distorted tetragonal antiprism CdN4O4 coordination geometry around the cadmium atom, resulting in coordination by four nitrogen atoms from two 5,5'-dmbipy ligands and four oxygen atoms from two acetate anions. The interaction of this complex to FS-DNA (fish sperm DNA) has also been studied by electronic absorption, fluorescence and gel electrophoresis techniques. Binding constant (Kb), Stern-Volmer constant (Ksv), number of binding sites (n) and bimolecular quenching rate constant (kq) have been calculated from these spectroscopic data. These results have revealed that the metal complex can bind effectively to FS-DNA via groove binding. The calculated thermodynamic parameters (ΔH°, ΔS° and ΔG°) show that hydrogen bonding and van der Waals forces have an important function in the Cd(II) complex-DNA interaction. The antibacterial effects of the synthesized cadmium complex have also been examined in vitro against standard bacterial strains: one Gram-positive (Staphylococcus aureus, ATCC 25923) and one Gram-negative (Escherichia coli, ATCC 25922) bacteria, using disk diffusion and macro-dilution broth methods. The obtained results show that the Cd(II) complex exhibits a marked antibacterial activity which is significantly better than those observed for its free ligand and metal salt for both Gram-positive and Gram-negative bacteria. However, this metal complex is a more potent antibacterial agent against the Gram-positive than that of the Gram-negative bacteria.Communicated by Ramaswamy H. Sarma.
- MeSH
- algoritmy MeSH
- antibakteriální látky chemie farmakologie MeSH
- Bacteria účinky léků MeSH
- DNA chemie MeSH
- kadmium chemie MeSH
- krystalografie rentgenová MeSH
- ligandy MeSH
- magnetická rezonanční spektroskopie MeSH
- mikrobiální testy citlivosti MeSH
- molekulární modely * MeSH
- molekulární struktura MeSH
- pyridiny chemická syntéza chemie farmakologie MeSH
- spektroskopie infračervená s Fourierovou transformací MeSH
- techniky syntetické chemie MeSH
- termodynamika MeSH
- vodíková vazba MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
A new thiourea ligand (HL), namely N-(4-chlorophenyl)morpholine-4-carbothioamide and its Co(III), Ni(II) and Ag(I) complexes (1a, 1b and 1c) were synthesized and investigated by Fourier-transform infrared, 1H NMR and UV-visible spectroscopies. The compounds HL and 1c were characterized by single-crystal X-ray crystallography revealing the triclinic space group P[Formula: see text] for both compounds. The inhibitory effect of HL ligand, 1a, 1b, and 1c complexes was investigated with in vitro tests on Gram-positive and Gram-negative bacteria. For the 1c complex, the results showed that the coordination of the HL to Ag(I) ion increased its antibacterial effect especially against E. coli. The assays also indicated that for the same bacteria strains, the new complexes showed higher activity than the ligand, with the relative activity 1c > 1b > 1a > HL. Moreover, all samples were more suitable antimicrobial agents against the Gram-negative than those of the Gram-positive bacteria. Eventually, the relationship between the structure and bactericidal activities of these specimens was examined by calculating frontier molecular orbital (HOMO and LUMO) energies using density functional theory method at the 6-31 G*/LANL2DZ level of theory.
- MeSH
- antibakteriální látky chemická syntéza chemie farmakologie MeSH
- gramnegativní bakterie účinky léků MeSH
- grampozitivní bakterie účinky léků MeSH
- komplexní sloučeniny chemická syntéza chemie farmakologie MeSH
- krystalografie rentgenová MeSH
- magnetická rezonanční spektroskopie MeSH
- mikrobiální testy citlivosti MeSH
- molekulární struktura MeSH
- morfoliny chemická syntéza chemie farmakologie MeSH
- spektrofotometrie ultrafialová MeSH
- spektroskopie infračervená s Fourierovou transformací MeSH
- thioamidy chemická syntéza chemie farmakologie MeSH
- thiomočovina metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
The monitoring of intracellular cholesterol homeostasis and trafficking is of great importance because their imbalance leads to many pathologies. Reliable tools for cholesterol detection are in demand. This study presents the design and synthesis of fluorescent probes for cholesterol recognition and demonstrates their selectivity by a variety of methods. The construction of dedicated library of 14 probes was based on heterocyclic (pyridine)-sterol derivatives with various attached fluorophores. The most promising probe, a P1-BODIPY conjugate FP-5, was analysed in detail and showed an intensive labelling of cellular membranes followed by intracellular redistribution into various cholesterol rich organelles and vesicles. FP-5 displayed a stronger signal, with faster kinetics, than the commercial TF-Chol probe. In addition, cells with pharmacologically disrupted cholesterol transport, or with a genetic mutation of cholesterol transporting protein NPC1, exhibited strong and fast FP-5 signal in the endo/lysosomal compartment, co-localizing with filipin staining of cholesterol. Hence, FP-5 has high potential as a new probe for monitoring cholesterol trafficking and its disorders.
- MeSH
- biologický transport MeSH
- buněčná membrána chemie metabolismus MeSH
- buněčné linie MeSH
- cholesterol analýza metabolismus MeSH
- fluorescenční barviva chemie MeSH
- fluorescenční mikroskopie metody MeSH
- lidé MeSH
- lyzozomální nemoci z ukládání diagnóza metabolismus MeSH
- pyridiny chemie MeSH
- sloučeniny boru chemie MeSH
- steroly chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
This study introduces a pair of newly synthesized silver complexes, [Ag2(HGly)2]n(NO3)2n (1) and [Ag(Nam)2]NO3·H2O (2) (Gly - glycine, Nam - nicotinamide), that were prepared and characterized by relevant methods in solid state (elemental, spectral, thermal and structural analysis) and their stability in solution was verified by 1H NMR measurements. Moreover, suitable reaction conditions were observed by potentiometry depending on pH in case of binary system Ag-Gly. X-ray analysis confirmed argentophilic interactions in complex 1 with an Ag1-Ag2 distance of 2.8018(6) Å. Antimicrobial testing indicates higher growth inhibition effect of complex 1 than complex 2. Moreover the effectivity of both complexes against bacteria (Staphylococcus aureus and Escherichia coli) is superior (or similar) to that of the commercially available Ag(I) sulfadiazine, AgSD (used, for example, in Dermazine cream). The binding of the Ag(I) complexes to calf thymus DNA was investigated using electronic absorption, fluorescence and circular dichroism spectrophotometry. The Stern-Volmer quenching constants obtained from the linear quenching plot were estimated in the range from 2.01×103 to 20.34×103M-1. The results of topoisomerase I and topoisomerase II (Topo I and Topo II) inhibition assay suggested that complex 2 inhibits the enzyme activity of both enzymes at a concentration of 2μM. The cytotoxicity of both complexes on L1210 leukemia cells was revealed to be approximately three times higher than that of cisplatin. Moreover, the new Ag(I) complexes also induced apoptosis of the leukemia cells. The high DNA binding activity of these complexes is considered to be responsible for their cytotoxic effects.
- MeSH
- aktivace enzymů účinky léků MeSH
- antiinfekční látky chemie farmakologie MeSH
- Bacteria účinky léků MeSH
- DNA-topoisomerasy metabolismus MeSH
- DNA chemie metabolismus MeSH
- glycin chemie MeSH
- inhibiční koncentrace 50 MeSH
- komplexní sloučeniny chemie farmakologie MeSH
- krystalografie rentgenová MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- niacinamid chemie MeSH
- protinádorové látky chemie farmakologie MeSH
- stříbro chemie farmakologie MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Samarcandin 1, a natural sesquiterpene-coumarin, was isolated as well as elucidated from F. assa-foetida which has significant effect in Iranian traditional medicine because of its medicinal attitudes. The crystal structure of samarcandin was determined by single-crystal X-ray structure analysis. It is orthorhombic, with unit cell parameters a=10.8204 (5)Å, b=12.9894 (7)Å, c=15.2467 (9)Å, V=2142.9 (2)Å(3), space group P212121 and four symmetry equivalent molecules in the unit cell. Samarcandin was isolated in order to study for its theoretical studies as well as its cellular toxicity as anti-cancer drug against two cancerous cells. In comparison with controls, our microscopic and MTT assay data showed that samarcandin suppresses cancer cell proliferation in a dose-dependent manner with IC50=11μM and 13 for AGS and WEHI-164 cell lines, respectively. Density functional theory (DFT) and time-dependent density functional theory (TD-DFT) of the structure was computed by three functional methods and 6-311++G(∗∗) standard basis set. The optimized molecular geometry and theoretical analysis agree closely to that obtained from the single crystal X-ray crystallography. To sum up, the good correlations between experimental and theoretical studies by UV, NMR, and IR spectra were found.
- MeSH
- krystalografie rentgenová MeSH
- kumariny chemie izolace a purifikace farmakologie MeSH
- kvantová teorie * MeSH
- lidé MeSH
- magnetická rezonanční spektroskopie MeSH
- molekulární modely MeSH
- molekulární struktura MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- proliferace buněk účinky léků MeSH
- protinádorové látky chemie izolace a purifikace farmakologie MeSH
- seskviterpeny chemie izolace a purifikace farmakologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
Per(2,3,6-tri-O-benzyl)-γ-cyclodextrin was debenzylated by DIBAL-H to produce a mixture of C6(I),C6(IV) and C6(I),C6(V) isomeric diols, which were separated and isolated. The C2-symmetrical C6(I),C6(V) diol was transformed into dithiol and dimerized to produce a γ-cyclodextrin duplex structure. A crystal structure revealed tubular cavity whose peripheries are slightly elliptically distorted. The solvent accessible volume of the cavity of the γ-CD duplex is about 740 Å(3). Due to this large inner space the duplex forms very stable inclusion complexes with steroids; bile acids examined in this study show binding affinities to the γ-cyclodextrin duplex in the range of 5.3 × 10(7) M(-1)-1.9 × 10(8) M(-1).
- MeSH
- dimerizace MeSH
- disulfidy chemie MeSH
- farmaceutická chemie metody MeSH
- gama-cyklodextriny chemická syntéza chemie MeSH
- imatinib mesylát chemie MeSH
- kalorimetrie MeSH
- kinetika MeSH
- koncentrace vodíkových iontů MeSH
- krystalografie rentgenová MeSH
- kyselina lithocholová chemie MeSH
- kyslík chemie MeSH
- magnetická rezonanční spektroskopie MeSH
- molekulární konformace MeSH
- rozpouštědla chemie MeSH
- steroidy chemie MeSH
- sulfhydrylové sloučeniny chemie MeSH
- termodynamika MeSH
- vazba proteinů MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
In this study isolation and structural elucidation of a homoisoflavonoid, 3-(3',4'-dihydroxybenzyl)-8-hydroxy-5,7-dimethoxychroman-4-one (Scillapersicone 1), is reported from Scilla persica HAUSSKN. The structure was solved by a single crystal X-ray analysis. The unit cell parameters are a=11.7676 (2)Å, b=20.1174 (4)Å, c=7.8645 (9)Å, β=93.544 (2)°, V=1858.23 (7)Å(3), monoclinic space group P21/c and four symmetry equivalent molecules in an unit cell. The structure was consistent with the UV, IR, 1D and 2D NMR, HRFAB-MS data. The optimized molecular geometry agrees closely that obtained from the single crystal X-ray crystallography. Furthermore, cytotoxicity of this compound was evaluated by MTT assay on AGS and WEHI-164 cancerous cell lines.
- MeSH
- flavonoidy chemie izolace a purifikace farmakologie MeSH
- fytogenní protinádorové látky chemie izolace a purifikace farmakologie MeSH
- krystalografie rentgenová MeSH
- lidé MeSH
- molekulární modely MeSH
- nádorové buněčné linie MeSH
- nádory farmakoterapie MeSH
- rostlinné extrakty chemie MeSH
- Scilla chemie MeSH
- viabilita buněk účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Publikační typ
- abstrakt z konference MeSH
