Synthesis of new 1,2,4-triazolines and 1,3,4-thiadiazolines from bithioureas

2,4-Disubstituted thiosemicarbazides 1 react with acyl isothiocyanates to give bithioureas 2 , which by the action of sodium ethanolate cyclize to 1,2,4-triazoline-3-thiones 3 and 5 , respectively. Treatment of 2 with methyl iodide yields 1,3,4-thiadiazoline-2-imines 8 isomeric with 3 . Compound 8d undergoes a thermal induced DIMROTH rearrangement to give 3d in good yield.     

Aqueous-phase synthesis of di-(η5-cyclopentadienyl)salicylato- anddi-(η5-cyclopentadienyl)phthalatotitanium(IV) complexes

Di-(⁵-cyclopentadienyl)dichlorotitanium(IV) reacts with salicylic acid or some of its ring-substituted derivatives in aqueous medium in the presence of alkali carbonate, giving (substituted) di-(⁵-cyclopentadienyl)-salicylatotitanium(IV) complexes(3). Analogously, although less efficaciously, the dichlorotitanium compound reacts with phthalic acid to give the phthalato complex(5), and with dipicolinic acid to yield the pyridinedicarboxylato compound(7). Meticulous control of the experimental conditions is necessary to minimize hydrolytic side reactions. The product complexes(3) and(5) can be recrystallized from chloroform, in which they dissolve completely when freshly prepared; prolonged storage at ambient temperature causes reductions in solubility. I.r. and n.m.r. spectroscopic features of the product complexes are presented.     

Active learning of constraints for weighted feature selection

Advances in Data Analysis and Classification - Pairwise constraints, a cheaper kind of supervision information that does not need to reveal the class labels of data points, were initially suggested...     

Screening for antioxidants in complex matrices using high performance liquid chromatography with acidic potassium permanganate chemiluminescence detection

The use of high performance liquid chromatography with acidic potassium permanganate chemiluminescence detection to screen for antioxidants in complex plant-derived samples was evaluated in comparison with two conventional post-column radical scavenging assays (2,2-diphenyl-1-picrylhydrazyl radical (DPPH) and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS(+))). In this approach, acidic potassium permanganate can react with readily oxidisable compounds (potential antioxidants), post-column, to produce chemiluminescence. Using flow injection analysis, experimental parameters that afforded the most suitable permanganate chemiluminescence signal for a range of known antioxidants were studied in a univariate approach. Optimum conditions were found to be: 1×10(-3)M potassium permanganate solution containing 1% (w/v) sodium polyphosphates adjusted to pH 2 with sulphuric acid, delivered at a flow rate of 2.5 mL min(-1) per line. Further investigations showed some differences in detection selectivity between HPLC with the optimised post-column permanganate chemiluminescence detection and DPPH and ABTS(+) assays towards antioxidant standards. However, permanganate chemiluminescence detection was more sensitive. Moreover, screening for antioxidants in green tea, cranberry juice and thyme using potassium permanganate chemiluminescence offers several advantages over the traditional DPPH and ABTS(+) assays, such as faster reagent preparation and superior stability; simpler post-column reaction manifold; and greater compatibility with fast chromatographic separations using monolithic columns.     

Separation of chitosan by degree of acetylation using simple free solution capillary electrophoresis

Chitosan is a biopolymer of increasing significance, as well as a renewable and sustainable material. Its main molecular characteristics are molar mass and degree of acetylation (composition). Precise average degrees of acetylation were measured by quantitative ¹H solution-state NMR spectroscopy. While number-average degrees of acetylation had already been determined by ¹H NMR spectroscopy, weight-average degrees of acetylation are also determined and may be more relevant for some properties, such as mechanical properties. We report the first separation of chitosan according to its degree of acetylation using free solution capillary electrophoresis. Capillary electrophoresis separates chitosan in the ‘critical conditions’: the molar mass plays little role and the separation is by the degree of acetylation. It characterises the heterogeneity of chitosan samples in terms of composition (dispersity of the distribution of degrees of acetylation). This heterogeneity (broad distribution of degrees of acetylation) cannot be neglected contrary to a common assumption found in the literature. This fast and easy separation will allow establishing a structure–property relationships.

Design,Synthesis and Biological Evaluation of Novel Pyrazolo[1,2,4]triazolopyrimidine Derivatives as Potential Anticancer Agents

Three novel pyrazolo-[4,3-e][1,2,4]triazolopyrimidine derivatives (1, 2, and 3) were designed, synthesized, and evaluated for their in vitro biological activity. All three compounds exhibited different levels of cytotoxicity against cervical and breast cancer cell lines. However, compound 1 showed the best antiproliferative activity against all tested tumor cell lines, including HCC1937 and HeLa cells, which express high levels of wild-type epidermal growth factor receptor (EGFR). Western blot analyses demonstrated that compound 1 inhibited the activation of EGFR, protein kinase B (Akt), and extracellular signal-regulated kinase (Erk)1/2 in breast and cervical cancer cells at concentrations of 7 and 11 µM, respectively. The results from docking experiments with EGFR suggested the binding of compound 1 at the ATP binding site of EGFR. Furthermore, the crystal structure of compound 3 (7-(4-bromophenyl)-9-(pyridin-4-yl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine) was determined by single crystal X-ray analysis. Our work represents a promising starting point for the development of a new series of compounds targeting EGFR.     

Diversity-oriented, one-pot, multi-component synthesis of substituted uracil derivatives

Abstract  

With the emergence of high throughput screening of bioactive molecules, there is constant need for the development of new strategies for diversity-oriented synthesis. We describe here a novel one-pot multicomponent reaction for the synthesis of uracil derivatives using easily available starting materials. This new synthetic strategy provides easy access to diverse uracil derivatives in moderate to good yields.     

Stability of various PLGA and lipid nanoparticles in temperature and in time and new technology for the preparation of liposomes for anticancer and antibiotic loading

Journal of Thermal Analysis and Calorimetry - The stabilizer, which is used during the preparation of Poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs), is of great importance for particle...