Anthraquinone profile, antioxidant and antimicrobial properties of bark extracts of Rhamnus catharticus and R. orbiculatus

The anthraquinone profile, antioxidant and antimicrobial activities as well as the total phenol and total flavonoid contents were determined in methanol extracts of the barks of Rhamnus catharticus L. and R. orbiculatus Bornm. The most abundant anthraquinone derivatives in R. catharticus were physcion (67.8%) and emodin (26.2%), while R. orbiculatus contained mostly physcion (81.3%) and chrysophanol (14.6%). R. catharticus displayed better activity in the beta-carotene-linoleic acid assay, as well as chelating activity, whereas its activity in the reducing power assay was significantly lower than that of R. orbiculatus. Both methanol extracts showed antimicrobial activity against all microbial species tested (Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Candida albicans, Aspergillus niger, Microsporum gypseum) with MIC values either equal to or lower than 2.50 mg/mL. R. catharticus and R. orbiculatus contained several anthranoid aglycones and their bark extracts demonstrated notable antioxidant and antimicrobial properties. The results obtained indicate the medicinal potential of these two species.     

Influence of phenylenediamine additions on the morphology and on the catalytic effect of polyaniline

The influence of para‐, ortho‐, and meta‐phenylenediamine (p‐, o‐, and m‐PDA) additions on the electrochemical synthesis of polyaniline has been investigated by the use of cyclic voltametry. It has been found that small additions (1 and 5 mmol L^?1) of PDA monomers influence significantly the polymerization rate. Whereas p‐PDA increases the polymerization rate, the addition of o‐ or m‐PDA slows it down. Therefore, a different number of potential cycling is necessary to obtain similar thickness of layers. The layers exhibit very different morphology, which changes from “spaghetti‐like” for polyaniline to “sponge‐like” for p‐PDA, to “pebble‐like” for o‐PDA and to “cauliflower‐like” for m‐PDA additions, respectively. The catalytic effect of the synthesized polymer layers has been tested. It has been found that all the layers exhibit catalytic effect in lowering the redox potential of hydroquinone/quinone tested reaction, but the rate of the electrocatalytic reaction varies depending on the PDA monomer added. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 1599–1608, 2004     

Application of flavonoids – quercetin and rutin – as new matrices for matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometric analysis of Pt(II) and Pd(II) complexes

Attempts are being made to overcome the resistance of tumour cells to platinum (Pt) drugs by the synthesis of new generations of Pt complexes, and it is important to find appropriate and simple methods for the characterization of those novel complexes. The additional applicability of such a method for the analysis of the interactions of metal complexes with biomolecules would be advantageous. Matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOFMS) seems to possess the capability to become this method of choice, since it could be applied to low‐mass complexes as well as for the analysis of large biomolecules. In this work the applicability of flavonoids – quercetin and rutin – as matrices for MALDI‐TOFMS analysis of dichlorido(ethylendiamine)platinum(II) ([PtCl₂(en)]), dichlorido(diaminocyclohexane)platinum(II) ([PtCl₂(dach)]) and chloride (diethylenetriamine) palladium(II) chloride ([PdCl(dien)]Cl) complexes is demonstrated. Spectra of Pt(II) and Pd(II) complexes recorded in the presence of quercetin and rutin are rather simple: Pt(II) complexes generate [M+Na]⁺ or [M+K]⁺ions, whereas the investigated Pd(II) complex gives ions generated by the loss of one Cl^? or HCl. Flavonoids give a relatively small number of well‐defined ions in the low‐mass region (at m/z 303.3 for quercetin and m/z 633.5 for rutin). Quercetin and rutin can be applied in much lower concentrations than other common MALDI matrices and require rather low laser intensity. We speculate that flavonoids stabilize the structures of the metal complexes and that they may be useful for the analysis of other biologically active metal complexes, thus implying their broader applicability. Copyright © 2009 John Wiley & Sons, Ltd.     

Synthesis and biological evaluations of mono‐ and bis‐ferrocene uracil derivatives

Mono‐ ( 3a – 3e and 4a – 4e ) and bis‐ferrocene ( 5a – 5e and 6a – 6e ) conjugated 5‐substituted uracil derivatives that are bridged by 1,2,3‐triazole linker were synthesized. The impact of ferrocene unit and spacer between ferrocene and triazole on radical scavenging potency was observed. Bis‐ferrocenyl uracil derivatives exhibited better antiproliferative activities than their mono‐ferrocenyl analogs. Bis‐ferrocenyl methyl‐ ( 5b ) and halogen‐substituted ( 5e , 6c , and 6d ) uracil derivatives showed pronounced and selective cytostatic activities on colon adenocarcinoma (CaCo‐2) and Burkitt lymphoma (Raji) cells, with higher potency and selectivity than the reference drug 5‐fluorouracil. Generation of reactive oxygen species (ROS) in CaCo‐2 and Raji cells when treated with compounds 5b , 5e , and 6d was observed. Bis‐ferrocenyl 5‐chlorouracil 6c induced significant disruption in mitochondrial membrane potential that is accompanied by activation of apoptosis in CaCo‐2, Raji, and acute lymphoblastic leukemia (CCRF‐CEM) cells, while 6d caused mitochondrial dysfunction and apoptosis induction in CaCo‐2 and Raji cells. Potent antiproliferative activity of 6c and 6d could be associated with mitochondrial membrane potential disruption accompanied by apoptosis induction. Our findings highlighted 6c and 6d with potent and selective antiproliferative activity on CaCo‐2, Raji, and CCRF‐CEM cells that may be associated with targeting cancer cell mitochondria, as a molecular target.     

Development of cyclodextrin-based extract of <Emphasis Type="Italic">Lotus corniculatus</Emphasis> as a potential substrate reduction therapy in mucopolysaccharidoses type III

A novel sustainable and eco-friendly procedure simultaneously combining the use of ultrasound irradiation and hydroxypropyl-β-cyclodextrin (HPβCD) complexation was used to extract phytochemicals from Lotus corniculatus and to prepare flavonoid rich extract having potential as substrate reduction therapy of mucopolysaccharidosis type III (MPS III), a rare autosomal recessive lysosomal storage disorder. For that instance, Box-Behnken design and response surface methodology was employed to statistically assess the influence of HPβCD concentration, ultrasonic power, and extraction time on the total phenolic compounds, total flavonoids, total phenolic acids and radical scavenging activity (RSA) of the extracts prepared, chosen as the responses indicative of the product quality and performance. The potential of such optimised extract to modulate accumulation of gylcosoaminoglycans (GAGs) was evaluated on the fibroblast obtained from patients suffering from MPS type III. Optimized extract prepared by 45 min extraction using HPβCD at concentration of 20 mM and ultrasonic irradiation of 648 W was rich in flavonoids (1.36 mg/mL) and showed notable RSA of 1.04 mg/mL. Freeze-dried extract, at concentration of 3 and 6 µg/mL, reduced GAG levels in skin fibroblasts by 33.97 and 50.08%, respectively, without any toxic effects at given doses, showing a potential to be considered as a part of the substrate reduction therapy of MPS III.     

Intramolecular N−H...O hydrogen bonding,quinoid effect,and partial π-electron delocalization in N-aryl Schiff bases of 2-hydroxy-1-naphthaldehyde: the crystal structures of planar N-(α-naphthyl)- and N-(β-naphthyl)-2-oxy-1-naphthaldimine

The structures of N-(-naphthyl)-2-oxy-1-naphthaldimine1 and N-(-naphthyl)-2-oxy-1-naphthaldimine2 have been investigated by X-ray analysis and by spectroscopic methods. Crystals of1 are monoclinic, space groupPn, with cell dimensionsa=10.823(3),b=5.826(2),c=11.899 (3) Å, and =99.66(3)°. Compound2 crystallizes in the orthorhombic space groupPca2₁ witha=17.564(3),b=6.314(2), andc=13.663(4) Å. The IR spectra exhibited neither N–H nor O–H stretching frequencies. The existence of theintramolecular hydrogen bonding of N–H...O type was predicted by spectroscopic experiment but unequivocally established by diffraction experiment in both cases1 and2. The molecules1 and2 are significantly planar with considerable quinoid effect at the 2-oxy-naphthaldimine moiety. Although essentially planar, both molecules1 and2 show the delocalization of -electrons only in the central part of the molecules including C=N imino group with pendent ring carbon atoms.Intermolecular attractions in the crystals belong to weak van der Waals interactions-between discrete planar molecules spatially arranged into the expectedherringbone motif in the solid state.     

Synthesis, spectroscopic properties and crystal structure determination of 2-(2-pyridin-4-yl-vinyl)-1H-benzimidazole derivatives

Substituted 2-(2-pyridin-4-yl-vinyl)-1H-benzimidazole derivatives 2, 3 and 6 were synthesized. 2-(2-Pyridin-4-yl-vinyl)-1H-benzimidazole 2 and 6-methyl-2-(2-pyridin-4-yl-vinyl)-1H-benzimidazole 3 were prepared by condensation reaction from 3-pyridin-4-yl-acrylic acid and corresponding 1,2-phenylenediamines in polyphosporic acid (PPA). 2,7,11-b-Triaza-benzo[c]fluorene 4 was prepared by photochemical dehydrocyclization reaction of ethanolic solution of 2-(2-pyridin-4-yl-vinyl)-1H-benzimidazole 2. 2-(2-Pyridin-4-yl-vinyl)-3H-benzimidazole-6-carbonitrile 6 was prepared by condensation reaction from 3-pyridin-4-yl-propenal and 4-cyano-1,2-phenylenediamine using p-benzoquinone as oxidants. The structure of novel benzimidazole derivatives has been studied by ¹H and ¹³C NMR, IR, MS, UV/Vis and fluorescence spectroscopy. The structure of 2-(2-pyridin-4-yl-vinyl)-1H-benzimidazole 2 was confirmed by X-ray single crystal structure analysis. The conformation of the molecule is E in regard to substituents position around vinyl double C=C bond. The non-planar molecules are mutually connected via the N–H···N and C–H···N type of intermolecular hydrogen bonds into infinite chains spreading along y axis.     

Synthesis and spectroscopic properties of furyl-phenyl-acrylates and naphthofurans and their interaction with ct-<Emphasis Type="Italic">DNA</Emphasis>

A series of novel substituted derivatives related to furyl-phenyl-acrylates and naphthofurans, was synthesized and characterized by UV/Vis and fluorescence spectroscopy. Acyclic compounds can undergo photochemical dehydrocyclization by visible light irradiation in order to obtain their cyclic derivatives. The interactions of the prepared compounds with calf thymus DNA was investigated by means of electronic absorption and fluorescence spectra. It is intriguing that addition of ct-DNA induced a fluorescence increase of acyclic derivatives, exactly the opposite of the strong fluorescence quenching observed for cyclic derivatives 10 and 12. Compound 11 showed decreasing fluorescence intensity for lower concentrations of ct-DNA, while increasing of fluorescence is observed for high excess of added ct-DNA. Correspondence: Grace Karminski-Zamola, Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev trg 20, HR-10000 Zagreb, Croatia.     

Use of an Octapeptide–Guanidiniocarbonylpyrrole Conjugate for the Formation of a Supramolecular β‐Helix that Self‐Assembles into pH‐Responsive Fibers

Peptides that adopt β‐helix structures are predominantly found in transmembrane protein domains or in the lipid bilayer of vesicles. Constructing a β‐helix structure in pure water has been considered difficult without the addition of membrane mimics. Herein, we report such an example; peptide 1 self‐assembles into a supramolecular β‐helix in pure water based on charge interactions between the individual peptides. Peptide 1 further showed intriguing transitions from small particles to helical fibers in a time‐dependent process. The fibers can be switched to vesicles by changing the pH value.