Brasiliensic and isobrasiliensic acids: isolation from Calophyllum brasiliense Cambess. and anti-Helicobacter pylori activity

The occurrence of chromanone derivatives has been noticed as a distinctive feature of the genus Calophyllum (Calophyllaceae). Previous studies have demonstrated that the extract of the stem bark of Calophyllum brasiliense and its chromanone-rich fractions show anti-ulcer activity in murine gastric ulcer models. In this work, brasiliensic and isobrasiliensic acids, the two main compounds of the n-hexane extract of the stem bark extract of C. brasiliense, were isolated by flash chromatography using silica gel impregnated with silver nitrate and their structures were elucidated by NMR techniques and mass spectrometry. ¹³C NMR data is available for the first time for both compounds. Brasiliensic and isobrasiliensic acids showed good in vitro bacteriostatic activity against Helicobacter pylori, and are responsible, at least in part, for the bacteriostatic anti-H. pylori activity of the n-hexane extract of the stem bark of C. brasiliense.     

Ferrocene/ferrocenium ion as a catalyst for the photodecomposition of chloroform

Irradiation (λ > 320 nm) of ferrocene in chloroform causes decomposition of chloroform and the accumulation of HCl, CCl₃OOH, and C₂Cl₆. This appears to occur initially through a cycle in which (a) ferrocene is oxidized to ferrocenium and tetrachloroferrate ions, (b) FeCl₄ ⁻ undergoes photodissociation, and (c) ferrocenium reoxidizes the chloroferrate(II) species. On extended photolysis, the concentrations of CCl₃OOH and FeCl₄ ⁻ build up and a competing cycle in which FeCl₄ ⁻ is restored through oxidation of the chloroferrate(II) species by CCl₃OOH accelerates the decomposition rate.     

Cytotoxicity and physico-chemical evaluation of acetylated and pegylated cellulose nanocrystals

The high hydrophilicity of cellulose nanocrystals (CNC) may result in poor dispersion in some matrices and solvents. So in this work, two different methodologies were used to reduce the hydrophilicity of CNC. In the first methodology, CNC were acetylated (CNC-Ac) in a mixture of acetic and hydrochloric acid, and in the second methodology, polyethylene glycol (PEG) was adsorbed onto CNC surface (CNC-PEG) under stirring in aqueous solution. CNC obtained by both methods were characterized by transmission electron microscopy (TEM), infrared spectroscopy (FTIR), X-ray diffraction (XRD), dynamic light scattering (DLS), zeta potential, and thermogravimetric analysis (TGA). Images of TEM showed that the intrinsic morphology of cellulose was preserved after both treatments. FTIR confirmed acetylation reaction by the presence of a new band at 1732 cm^?1 (acetate groups) and the consumption of OH groups. XRD showed a reduction in the crystallinity index for both applied methodologies. DLS showed reduced stability in water for CNC-Ac and CNC-PEG. Values of zeta potential changed after acetylation, from ??45 mV (CNC) to ??1 mV (CNC-Ac), and after adsorption of PEG, to ??26.7 mV (CNC-PEG). TGA showed a reduction in the thermal stability after both treatments and a change in the main degradation behavior for CNC-PEG. MTT assays showed that both proposed functionalizations induce cell proliferation, being even more evident for acetylation because, in addition to viability increase with time, it increased with the sample concentration.     

Diversity of P450 enzymes in the biosynthesis of natural products

Covering: 1985 to 2012Diverse oxygenation patterns of natural products generated by secondary metabolic pathways in microorganisms and plants are largely achieved through the tailoring reactions catalysed by cytochrome P450 enzymes (P450s). P450s are a large family of oxidative hemoproteins found in all life forms from prokaryotes to humans. Understanding the reactivity and selectivity of these fascinating C-H bond-activating catalysts will advance their use in generating valuable pharmaceuticals and products for medicine, agriculture and industry. A major strength of this P450 group is its set of established enzyme-substrate relationships, the source of the most detailed knowledge on how P450 enzymes work. Engineering microbial-derived P450 enzymes to accommodate alternative substrates and add new functions continues to be an important near- and long-term practical goal driving the structural characterization of these molecules. Understanding the natural evolution of P450 structure-function should accelerate metabolic engineering and directed evolutionary approaches to enhance diversification of natural product structures and other biosynthetic applications.     

Application and Modification of Cyclometalated Ruthenium(II) Complex [Ru(o-C6H4-2-C5H4N)- (MeCN)4]PF6 for Atom Transfer Radical Polymerization

Polymerizations of n-butyl acrylate (BA), methyl methacrylate (MMA) and styrene (St) were promoted by the Ru(II) cyclometalated complex with labile MeCN ligand in the presence of Al(OiPr)₃. The polymerization proceeds via radical mechanism and requires the loss of MeCN ligand. The poor control over the polymerizations can be explained in terms of the traditional ATRP scheme. However, the controllability may be significantly improved by addition of reducing SnCl₂. Mechanism of the process is proposed.     

Syntheses and structure-activity relationships of novel 3′-difluoromethyl and 3′-trifluoromethyl-taxoids

A series of novel 3′-difluoromethyl-taxoids and 3′-trifluoromethyl-taxoids with modifications at the C2 and C10 positions were synthesized and evaluated for their in vitro cytotoxicities against human breast carcinoma (MCF7-S, MCF7-R, LCC6-WT, LCC6-MDR), non-small cell lung carcinoma (H460) and colon adenocarcinoma (HT-29) cell lines. These second-generation fluoro-taxoids exhibited several times to more than 20 times better potency than paclitaxel against drug-sensitive cancer cell lines, MCF7-S, LCC6-WT, H460, and HT-29. These fluoro-taxoids also possess two orders of magnitude higher potency than paclitaxel against drug-resistant cancer cell lines, MCF7-R and LCC6-MDR. Structure-activity relationship study shows the importance of the C10 modification for increasing the activity against multidrug-resistant cancer cell lines. Effects of the C2-benzoate modifications on the potency in the 3′-difluoromethyl-taxoid series are very clear (i.e., F < MeO < Cl < N₃), while those in the 3′-trifluoromethyl-taxoid series are less obvious. Also, different trends in the sensitivity to the C2-substitution are observed between drug-sensitive cell lines and drug-resistant cancer cell lines that overexpress efflux pumps.     

Application of high-performance liquid chromatography-nuclear magnetic resonance coupling to the identification of limonoids from mahogany tree (Switenia macrophylla, Meliaceae) by stopped-flow 1D and 2D NMR spectroscopy

Separation and characterization of limonoids from Switenia macrophylla (Meliaceae) by HPLC-NMR technique has been described. Analyses were carried out using reversed-phase gradient HPLC elution coupled to NMR (600 MHz) spectrometer in stopped-flow mode. Separated peaks were collected into an interface unit prior to NMR measurements, which were performed with suppression of solvent signals by shaped pulses sequences. Structure elucidation of the limonoids was attained by data obtained from 1H NMR, TOCSY, gHSQC and gHMBC spectra without conventional isolation that is usually applied in natural products studies.     

Physical–chemical characterization of new anti-inflammatory agent (LPSF/GQ-130) and evaluation of its thermal compatibility with pharmaceutical excipients

LPSF/GQ-130 is a drug candidate, according to reports about its significant anti-inflammatory activity and non-toxicity demonstrated in an acute preclinical study. Despite this, knowledge of its physical–chemical properties is insufficient for the development of medicines. Thus, this work aimed to characterize the raw material at its molecular, particle, and agglomerate level as well as evaluate its thermal compatibility to pharmaceutical excipients. Through spectrometric techniques the molecular structure of the substance was confirmed. For thermal analysis its melting (171.3–176.5 °C) and degradation (238.3–297.4 °C) ranges, besides its purity (99.37 %), were determined. The kinetic non-isothermal degradation supplied the order of thermal reaction (0), the activation energy (96.14 kJ mol^?1) and the frequency factor (3.130 × 10^?7 min^?1). The diffraction of X-rays presented well defined signs in the angles 5.5°, 16.3°, and 44.18° 2θ, suggesting crystalline structure. Scanning electronic microscopy exhibited needle morphology. LPSF/GQ-130 presented Type-III isotherm adsorption/desorption, with a superficial area of 81.3529 m² g^?1 and water content calculated at 1 % using the Karl Fisher method. Laser granulometry calculated its granulometry between 11.65 and 13.10 μm, thus it was characterized as a very fine powder. The prototype was classified as insoluble in water (<0.0187 μg mL^?1) and soluble in acetone and acetonitrile, and exhibits instability in basic pH (100 %) and oxidative conditions (30–70 %). In thermal compatibility the excipients PVP K-30, Compritol^® 888 ATO, and MYRJ^® 59 seem to exercise a protective thermal activity for the prototype.     

Nanoaggregates of copper porphyrazine in floating layers and Langmuir-Schaefer films

Aggregation behavior of unsubstituted copper porphyrazine (CuPaz) on the water surface was studied by analysis of compression curves, Brewster angle microscopy (BAM), and optical spectroscopy. The structure and stability of the CuPaz aqua aggregates in the floating layers are determined by hydration degree that depends on initial surface concentration and surface pressure. Langmuir-Schaefer (LS) films of CuPaz were prepared by deposition of the variously structured floating layers and studied by X-ray scattering technique and optical spectroscopy. Stable and labile structures were detected and compared with the floating CuPaz aqua aggregates. Conditions of formation of the stable four-stacked nanoaggregates in LS films were determined. A model comprising both nucleation of CuPaz on the water surface and structural transformations in the solid films is proposed.