A series of novel Ga(III)-pyridine carboxylates ([Ga(Pic)3]·H2O (GaPic; HPic = picolinic acid), H3O[Ga(Dpic)2]·H2O (GaDpic; H2Dpic = dipicolinic acid), [Ga(Chel)(H2O)(OH)]2·4H2O (GaChel; H2Chel = chelidamic acid) and [Ga(Cldpic)(H2O)(OH)]2 (GaCldpic; H2Cldpic = 4-chlorodipicolinic acid)) have been synthesized by simple one-step procedure. Vibrational spectroscopy (mid-IR), elemental analysis, thermogravimetric analysis and X-ray diffraction confirmed complexes molecular structure, inter and intramolecular interactions and their influence to spectral and thermal properties. Moreover, complex species speciation was described in Ga(III)-HPic and Ga(III)-H2Dpic systems by potentiometry and 1H NMR spectroscopy and mononuclear complex species were determined; [Ga(Pic)2]+ (logβ021 = 16.23(6)), [Ga(Pic)3] (logβ031 = 20.86(2)), [Ga(Dpic)2]- (logβ021 = 15.42(9)) and [Ga(Dpic)2(OH)]2- (logβ-121 = 11.08(4)). To confirm the complexes stability in 1% DMSO (primary solvent for biological testing), timescale 1H NMR spectra were measured (immediately after dissolution up to 96 h). Antimicrobial activity evaluated by IC50 (0.05 mM) is significant for GaDpic and GaCldpic against difficult to treat and multi-resistant P. aeruginosa. On the other hand, the GaPic complex is most effective against Jurkat, MDA-MB-231 and A2058 cancer cell lines and significantly also decreases the HepG2 cancer cells viability at 75 and 100 μM concentrations in a relatively short time (up to 48 h). In addition, fluorescence measurements have been used to elucidate bovine serum albumin binding activity between ligands, Ga(III) complexes and bovine serum albumin.
A series of novel acridine N-acylhydrazone derivatives have been synthesized as potential topoisomerase I/II inhibitors, and their binding (calf thymus DNA-ctDNA and human serum albumin-HSA) and biological activities as potential anticancer agents on proliferation of A549 and CCD-18Co have been evaluated. The acridine-DNA complex 3b (-F) displayed the highest Kb value (Kb = 3.18 × 103 M-1). The HSA-derivatives interactions were studied by fluorescence quenching spectra. This method was used for the calculation of characteristic binding parameters. In the presence of warfarin, the binding constant values were found to decrease (KSV = 2.26 M-1, Kb = 2.54 M-1), suggesting that derivative 3a could bind to HSA at Sudlow site I. The effect of tested derivatives on metabolic activity of A549 cells evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide or MTT assay decreased as follows 3b(-F) > 3a(-H) > 3c(-Cl) > 3d(-Br). The derivatives 3c and 3d in vitro act as potential dual inhibitors of hTopo I and II with a partial effect on the metabolic activity of cancer cells A594. The acridine-benzohydrazides 3a and 3c reduced the clonogenic ability of A549 cells by 72% or 74%, respectively. The general results of the study suggest that the novel compounds show potential for future development as anticancer agents.
- MeSH
- akridiny chemie MeSH
- inhibitory topoisomerasy II farmakologie MeSH
- interkalátory MeSH
- lidé MeSH
- lidský sérový albumin chemie MeSH
- protinádorové látky * chemie MeSH
- vazebná místa MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Phytochemical investigations of Matricaria chamomilla L. (Asteraceae) stated the presence of several compounds with an established therapeutic and antioxidant potential. The chamomile non-enzymatic antioxidant system includes low molecular mass compounds, mainly polyphenols such as cinnamic, hydroxybenzoic and chlorogenic acids, flavonoids and coumarins. The objective of this work was to evaluate the role of the non-enzymatic antioxidant system after stimulation by ethylene in tetraploid chamomile plants. Seven days of ethylene treatment significantly increased the activity of phenylalanine ammonia-lyase, which influenced the biosynthesis of protective polyphenols in the first step of their biosynthetic pathway. Subsequently, considerable enhanced levels of phenolic metabolites with a substantial antioxidant effect (syringic, vanillic and caffeic acid, 1,5-dicaffeoylquinic acid, quercetin, luteolin, daphnin, and herniarin) were determined by HPLC-DAD-MS. The minimal information on the chlorogenic acids function in chamomile led to the isolation and identification of 5-O-feruloylquinic acid. It is accumulated during normal conditions, but after the excessive effect of abiotic stress, its level significantly decreases and levels of other caffeoylquinic acids enhance. Our results suggest that ethephon may act as a stimulant of the production of pharmaceutically important non-enzymatic antioxidants in chamomile leaves and thus, lead to an overall change in phytochemical content and therapeutic effects of chamomile plants, as well.
- MeSH
- antioxidancia metabolismus MeSH
- biosyntetické dráhy fyziologie MeSH
- ethyleny metabolismus MeSH
- fenoly metabolismus MeSH
- fenylalaninamoniaklyasa metabolismus MeSH
- fyziologický stres fyziologie MeSH
- heřmánek, heřmánkovec, rmen, rmenec metabolismus MeSH
- kyselina chinová analogy a deriváty metabolismus MeSH
- kyselina chlorogenová metabolismus MeSH
- kyseliny kávové metabolismus MeSH
- listy rostlin metabolismus MeSH
- Matricaria metabolismus MeSH
- polyfenoly metabolismus MeSH
- rostlinné extrakty metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
Two silver(I) aminoacidate complexes {[Ag4(L-HAla)4(NO3)3]NO3}n (AgAla, complex 1, Ala = alanine) and {[Ag(L-Phe)]}n (AgPhe, complex 2, Phe = phenylalanine) were prepared and characterized by elemental, spectral analysis (FT-IR, NMR techniques) and single crystal X-ray analysis in solid state and their solution stability was measured in biological testing time-scale by 1H NMR. The bridging coordination modes of the zwitterionic Ala and deprotonated Phe ligands led to the formation of 1D polymeric chains of the complexes. The significant argentophilic interactions are presented in the structure of AgAla. Antimicrobial testing of prepared Ag(I) complexes was evaluated by IC50 and MIC values and were compared with AgGly, silver(I) sulfadiazine and AgNO3 samples. Moreover, MTS test was used to the testing of broad range antiproliferative activity of studied compounds against different cancer cell lines and also to the investigation of calf thymus DNA interactions by absorption spectroscopy, fluorescence spectroscopy, Ethidium bromide/Hoechst 33258 displacement experiments and circular dichroism spectroscopy. To evaluate the pUC19 DNA fragmentation by silver(I) complexes, the agarose gel electrophoresis was used. In addition to biological evaluation we used lipophilicity measurement results in the discussion about structure-activity relationship (SAR).
- MeSH
- alanin chemie metabolismus farmakologie MeSH
- antibakteriální látky chemie metabolismus farmakologie MeSH
- antifungální látky chemie metabolismus farmakologie MeSH
- Candida parapsilosis účinky léků MeSH
- DNA metabolismus MeSH
- Escherichia coli účinky léků MeSH
- fenylalanin chemie metabolismus farmakologie MeSH
- katalýza MeSH
- komplexní sloučeniny chemie metabolismus farmakologie MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- molekulární struktura MeSH
- nádorové buněčné linie MeSH
- proliferace buněk účinky léků MeSH
- protinádorové látky chemie metabolismus farmakologie MeSH
- screeningové testy protinádorových léčiv MeSH
- skot MeSH
- Staphylococcus aureus účinky léků MeSH
- štěpení DNA účinky léků MeSH
- stříbro chemie MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- skot MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
V súčasnej dobe existuje 750 druhov húb rodu Cordyceps. Vysoká cena prírodného Cordycepsu a jej nedostatok v prírode spôsobil, že sa pozornosť upriamila na jej pestovanie, kultiváciu v laboratórnych podmienkach. Dopyt po tejto "hube-parazitovi" je aj v dnešnej dobe pomerne vysoký, čo dokazuje aj množstvo komerčných výživových doplnkov. Fytochemická diverzita zabezpečila, že Cordyceps sa používa ako imunomodulátor, antioxidant; má protirakovinové, protizápalové, antidiabetické, antibakteriálne a anti-HIV účinky. Práca sa zaoberá NMR a IR analýzou prírodných látok izolovaných z dvoch druhov húb rodu Cordyceps: Cordyceps sinensis MFTCCB025/0216, MFTCCB026/0216 a Paecilomyces hepiali MFTCCB023/0216. Tie boli umelo kultivované na dvoch substrátoch ryže (Oryza sativa Indica a Oryza sativa Japonica). Celkovo sa analyzovalo päť metanolových extraktov, ktoré boli pripravené refluxovaním pomletého materiálu húb. Na stanovenie kvality a kvantity majoritných chemických zlúčenín sa využila 1D a 2D NMR analýza, ktorej riešením 1H, 13C, COSY, NOESY, HSQC, HMBC a DEPT spektier sa priradili protóny a uhlíky jednotlivým organickým zlúčeninám. Ako doplnková analýza na stanovenie funkčných skupín sa zvolila IR spektroskopia. V extraktoch boli identifikované ako majoritné nasledujúce chemické zlúčeniny: kyselina linolová, kyselina olejová, manitol; ako minoritné tyrozín, alanín, močovina a iné biologicky zaujímavé látky.
There exist about 750 species of Cordyceps at present. A high price of natural Cordyceps and its lack in nature caused that the attention has been focused to its cultivation in laboratory conditions. The demand for this "fungus-parasite" is still quite high nowadays, as shown by the amount of commercial nutritional supplements. Phytochemical diversity has ensured that Cordyceps is used as an immunomodulatory and an antioxidant; it has anti-cancer, anti-inflammatory, anti-diabetic, antibacterial, anti-HIV effects. In the present study we focused on NMR and IR analyses of natural substances isolated from two species of Cordyceps: Cordyceps sinensis MFTCCB025/0216, MFTCCB026/0216 and Paecilomyces hepiali MFTCCB023/0216. Two types of rice substrates (Oryza sativa Indica and Oryza sativa Japonica) were used for cultivation. A total of five methanol extracts obtained by a reflux method of the ground mushroom were analysed. To determine the quality and quantity of the major chemical compounds, 1D and 2D NMR analysis has been used with 1H, 13C, COSY, NOESY, HSQC, HMBC and DEPT spectra. IR spectroscopy was chosen as a complementary analysis to determine functional groups. Linoleic acid, oleic acid and mannitol were identified as major compounds of the methanol extracts. Tyrosine, alanine, urea and the others biologically interesting substances were found as minor components.
- Klíčová slova
- Paecilomyces hepiali,
- MeSH
- Cordyceps * chemie MeSH
- kyselina linolová MeSH
- kyselina olejová MeSH
- magnetická rezonanční spektroskopie MeSH
- mannitol MeSH
- Paecilomyces * chemie MeSH
- spektrofotometrie infračervená MeSH
- tradiční čínská medicína MeSH
- Publikační typ
- 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
Three new diphenylsubstituted spirotriazolidine- and thiazolidinone-acridines were prepared and their interaction with calf thymus DNA investigated with UV-vis, fluorescence, circular dichroism spectroscopy and viscometry. The binding constants K were estimated to range from 0.34 to 0.93 × 10(4) M(-1). UV-vis, fluorescence and circular dichroism measurements indicated that the compounds act as effective DNA-interacting agents. Electrophoretic separation proved that ligands inhibited topoisomerase I and II. The biological activity of compounds 3, 5 &6 at several different concentrations (10, 20 and 50 μM) was evaluated both 48 h and 72 h following their addition to HL-60 cancer cells. The results were analysed using various different techniques (MMP detection, changes in metabolic activity/viability and analysis of cell cycle distribution). Acridine was also used as the positive control in these assays. The results from MMP analysis demonstrate the strong effect of 3-diphenylamino-2-(acridin-9-yl)imino-1,3-thiazolidin-4-one (5) on mitochondrial physiology. Cell viability analysis showed that acridine derivatives 3 and 6 were less effective than derivative 5 and the acridine control.
- MeSH
- akridiny chemie MeSH
- DNA-topoisomerasy I metabolismus MeSH
- DNA-topoisomerasy typu II metabolismus MeSH
- DNA metabolismus MeSH
- HL-60 buňky MeSH
- inhibitory topoisomeras chemická syntéza chemie metabolismus farmakologie MeSH
- lidé MeSH
- protinádorové látky chemická syntéza chemie metabolismus farmakologie MeSH
- skot MeSH
- spirosloučeniny chemická syntéza chemie metabolismus farmakologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- skot MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
