New Estrone Oxime Derivatives: Synthesis,Cytotoxic Evaluation and Docking Studies

The interest in the introduction of the oxime group in molecules aiming to improve their biological effects is increasing. This work aimed to develop new steroidal oximes of the estrane series with potential antitumor interest. For this, several oximes were synthesized by reaction of hydroxylamine with the 17-ketone of estrone derivatives. Then, their cytotoxicity was evaluated in six cell lines. An estrogenicity assay, a cell cycle distribution analysis and a fluorescence microscopy study with Hoechst 3358 staining were performed with the most promising compound. In addition, molecular docking studies against estrogen receptor α, steroid sulfatase, 17β-hydroxysteroid dehydrogenase type 1 and β-tubulin were also accomplished. The 2-nitroestrone oxime showed higher cytotoxicity than the parent compound on MCF-7 cancer cells. Furthermore, the oximes bearing halogen groups in A-ring evidenced selectivity for HepaRG cells. Remarkably, the Δ^9,11-estrone oxime was the most cytotoxic and arrested LNCaP cells in the G₂/M phase. Fluorescence microscopy studies showed the presence of condensed DNA typical of prophase and condensed and fragmented nuclei characteristic of apoptosis. However, this oxime promoted the proliferation of T47-D cells. Interestingly, molecular docking studies estimated a strong interaction between Δ^9,11-estrone oxime and estrogen receptor α and β-tubulin, which may account for the described effects.     

Right triangular spherical dihedral f-tilings: the {\left(\frac{\pi}{2},\frac{\pi}{3},\frac{\pi}{5}\right)} , {\left(\frac{\pi}{2},\frac{2\pi}{5},\frac{\pi}{5}\right)} family

In this paper we classify all the dihedral f-tilings of the sphere whose prototiles are the right triangles of angles ${\left(\frac{\pi}{2},\frac{\pi}{3},\frac{\pi}{5}\right)}$ and ${\left(\frac{\pi}{2},\frac{2\pi}{5},\frac{\pi}{5}\right)}$ . Some combinatorial aspects of the structure of each f-tiling are given.     

Heuristic methods for the sectoring arc routing problem

The sectoring arc routing problem (SARP) is introduced to model activities associated with the streets of large urban areas, like municipal waste collection. The aim is to partition the street network into a given number of sectors and to build a set of vehicle trips in each sector, to minimize the total duration of the trips. Two two-phase heuristics and one best insertion method are proposed. In the two-phase methods, phase 1 constructs the sectors using two possible heuristics, while phase 2 solves a mixed capacitated arc routing problem (MCARP) to compute the trips in each sector. The best insertion method determines sectors and trips simultaneously. In addition to solution cost, some evaluation criteria such as imbalance, diameter and dispersion measures are used to compare algorithms. Numerical results on large instances with up to 401 nodes and 1056 links (arcs or edges) are reported and analysed.     

A study on red lead degradation in a medieval manuscript Lorvão Apocalypse (1189)

The mechanisms of red lead degradation were studied in a medieval Portuguese codex, Lorvão Apocalypse (1189), by Raman microscopy (µ‐Raman) and micro‐X‐ray diffraction (µ‐XRD). The range of pigments found for the illuminations is mainly limited to vermilion, orpiment and red lead. Micro‐Fourier transform infrared spectroscopy (µ‐FTIR) determined that the pigments were applied in a proteinaceous binding medium. In the red and orange colours, arsenic (As) was determined, by micro‐energy dispersive X‐ray fluorescence (µ‐EDXRF), to be ranging 1–4% (wt %). For those colours, lead white and calcium carbonate were found as fillers whereas orpiment was applied as a pure pigment. Raman microscopy identified, unequivocally, the degradation product of red lead as galena [lead (II) sulphide, PbS]. To determine the main factors affecting red lead degradation, a set of accelerating ageing experiments was designed to assess the influence of extenders and of the two other pigments, vermilion and orpiment. The experiments were followed by µ‐Raman, µ‐EDXRF and XRD. Raman microscopy results for the simulation of degradation of red lead, in the presence of orpiment, are in agreement to what was found in the Lorvão Apocalypse, galena being the main degradation product; also in common is a Raman band at ca. 810 cm⁻¹, which was attributed to a lead arsenate compound. It was concluded that in Lorvão Apocalypse, the degradation of red lead was a result of its reaction with orpiment. Copyright © 2009 John Wiley & Sons, Ltd.