New pyranosyl cembranoid diterpenes from Sarcophyton trocheliophorum

During our continual searching programme for novel bioactive metabolites from Sarcophyton trocheliophorum, collected from Red Sea, we describe herein the isolation and structural elucidation of further two new pyrane-based cembranoid diterpenes: 9-hydroxy-7,8-dehydro-sarcotrocheliol (1) and 8,9-expoy-sarcotrocheliol acetate (2), along with the well-known sarcotrocheliol acetate (3), (+)-sarcophine (4), (+)-sarcophytoxide (5) and (-)-sarcophytoxide (6). The chemical structures of compounds 1 and 2 were determined on the basis of 1D and 2D NMR (¹H, ¹³C, ¹H–¹H COSY, HMQC, HMBC and NOE), mass spectra (ESI and HR-ESIMS) and by comparison with related structures. The antimicrobial activities of the reported compounds 1–6 were investigated. According to the molecular docking study of compounds 1–6 using 3D structure of α,β tubulin in complex with taxol (PDB code 1JFF) and epothilone A (PDB code 1TVK), sarcophine (4) displayed the highest affinity towards both crystal structures, followed by 5 and 6, meanwhile pyrane-based cembranoid diterpenes (1–3) showed less affinity.     

Synthesis and spectroscopic studies of methoxy-substituted phenylthienylnicotinamidines

Abstract

Five thienylnicotinamidine derivatives 5a–e were prepared from their corresponding nicotinonitriles 3a–e on treatment with lithium trimethylsilylamide [LiN(TMS)₂] followed by hydrolysis using ethanolic/HCl (gas). The nicotinonitriles 3a–e were prepared via Suzuki coupling reaction of bromothienyl derivative 1 with the appropriate phenylboronic acids 2a–e. The DFT calculation was used to optimize the geometric structure of the newly synthesized nicotinamidines. The comparison of DFT/B3LYP calculated spectral data (¹H-NMR and ¹³C-NMR) with the experimental data showed acceptable agreement. Mass fragmentation patterns of 3,4-dimethoxyphenyl, 3,5-dimethoxyphenyl, and 3,4,5-trimethoxyphenyl thienylnicotinamidine derivatives were investigated.     

Baclofen impurities: Facile synthesis and novel environmentally benign chromatographic method for their simultaneous determination in baclofen

An efficient, economic and high yielding method was described for the synthesis of baclofen (BAC) pharmacopoeial impurities (impurity A and impurity B) which can be used for gram‐scale synthesis. Furthermore, a novel ecofriendly thin‐layer chromatographic TLC–densitometric method was established and validated for the determination of BAC and its synthesized impurities. The developed TLC–densitometric method is based on the chromatographic separation using TLC plates (60 F₂₅₄) using a green mobile phase of ethyl acetate–methanol–ammonia solution, 33% (8:2:0.1, by volume) with UV scanning at 220 nm. The proposed method was validated with respect to International Conference on Harmonization guidelines. The validated method was successfully applied for determination of BAC in pure form and in its commercial dosage form. Additionally, the greenness profile of the developed method was evaluated and compared with those of the reported chromatographic methods. The developed method was found to be superior to the published methods, being environmentally benign.     

Interaction in the geometro-differential conception of extended particles and the Galilei semigroup of trajectories

Along the lines of a previous work, the geometrical structure of Hibert bundles describing extended quantum free particles is repeated with Galilei external and internal independent symmetries. Then, in order to introduce the interaction, this structure is extended by replacing configuration and momentum spaces by the socelled spaces of trajectories and extended velocity boosts, respectively. These provide representations giving the probability amplitudes for the particle to follow certain trajectories. The interaction can be introduced in the transformation law from functions on the space of trajectories (free dynamics) to functions on spacetime (intracting dynamics). This transformation law, which makes use of a universal distribution, is seen as a functional in our work according to a quantum functional theory which generalizes the ideas of de Broglie. Intertwining of induced representations gives the free propagator in the space of trajectories and, henceforth, the propagator with interaction in space-time for the extended particle.     

Chromatographic analysis of ledipasvir and sofosbuvir: New treatment for chronic hepatitis C infection with application to human plasma

Sofosbuvir (SOF) and ledipasvir (LED) are recently approved and coformulated as directly acting antiviral agents used for treatment of hepatitis C virus (HCV). A reversed phase high performance liquid chromatography - diode array detector (RP-HPLC/DAD) method was developed and validated for the first time for the analysis of newly formulated anti-HCV combination, in pure form, pharmaceutical formulation and in human plasma. In the developed method, separation was performed on Zorbax® Eclipse C18 column using a gradient mixture of acetonitrile–water as a mobile phase and scanning was performed at 260?nm (for SOF) and 330?nm (for LED). The two drugs were completely separated from each other and from plasma, where plasma peak appeared at 2.76?±?0.05?min, SOF at 4.25?±?0.05, and LED at 7.35?±?0.05. The developed method showed high sensitivity, the drugs showed linearity in the range of 1–45?µg/mL for both pure form and spiked human plasma. Three freeze–thaw cycles were performed separately at two different temperatures, ?8 and ?20°C. No significant loss of the studied drugs were observed during repeated thawing and freezing. Validation parameters such as accuracy, precision, robustness, and ruggedness were tested in compliance with USP recommendations, where acceptable results were obtained. Applying to pharmaceutical formulation showed no interference from tablet excipients.     

Classification of Nilpotent Malcev Algebras of Small Dimensions Over Arbitrary Fields of Characteristic not 2

The paper is devoted to classify all of the nilpotent Malcev algebras of dimension ≤ 6 over an arbitrary base field ?? of characteristic not 2. We also classify all 7-dimensional non-Lie nilpotent Malcev algebras which are not metabelian over any field of characteristic not 2.     

Synthesis and QSAR Study of Some Novel Heterocyclic Derivatives as In Vitro Cytotoxic Agents

2,3‐Diaryloxirane‐2,3‐dicarbonitriles have employed in heterocyclic synthesis in many organic reactions. Authors highlight its use as intermediate in the synthesis of various organic compounds through the reaction with different nitrogen nucleophiles as methyl hydrazine, thiourea, thiosemicarbazide, methylglycinate, and others to furnish new heterocyclic derivatives. They are also used as key starting materials to construct some important heterocycles. Structures of all newly synthesized products are substantiated by studying their micro analytical and spectral data. Some of newly synthesized compounds were evaluated for their in vitro cytotoxic effects against a panel of three human tumor cell lines, namely, Hep‐G2, Hela, and MCF‐7. Most of the newly synthesized compounds ( 1a , 2a , 2d , 3 , 4 , 5 , 6a , 6c , 6d , 7a , and 7b ) inhibited cell proliferation with IC₅₀ values in range of 0.52–5.21 μΜ. For activity against HepG2 cell line, compounds 5 , 6a , 6d , and 7b emerged as the most active members. The Hela cell line showed highest sensitivity toward compounds 2a , 2d , and 6c whereas compounds 2d and 6c showed the highest inhibitory activity against MCF‐7 cell line.     

Induced secondary metabolites from the endophytic fungus Aspergillus versicolor through bacterial co-culture and OSMAC approaches

Two new cryptic 3,4-dihydronaphthalen-(2H)-1-one (1-tetralone) derivatives, aspvanicin A (1) and its epimer aspvanicin B (2), as well as several known cryptic metabolites (3–8), were obtained from the ethyl acetate extract of the co-culture of the endophytic fungus Aspergillus versicolor KU258497 with the bacterium Bacillus subtilis 168 trpC2 on solid rice medium. When A. versicolor was cultured axenically in liquid Wickerham medium supplemented with 3.5% DMSO, an additional three known secondary metabolites (9–11) were isolated that were lacking when the fungus was fermented on rice medium. The structures of the new compounds were elucidated using one- and two-dimensional NMR spectroscopy as well as HRESIMS. The relative and absolute configurations of 1 and 2 were determined by the combination of NMR and electronic circular dichroism (ECD) analysis aided by DFT conformational analysis and TDDFT-ECD calculations. The ECD calculations revealed that although the sign of the blue-shifted overlapping n-π¹ ECD transition follows the helicity rule of cyclic aryl ketones, the calculation of low-energy conformers and ECD spectra was necessary to determine the stereochemistry. All metabolites were assessed for their antibacterial and cytotoxic activities; one of the new diastereomers, compound 2, showed moderate cytotoxic activity against the mouse lymphoma cell line L5178Y.     

新开花粉蛋白的盐酸胍去折叠过程

本文利用荧光光谱和园二色光谱了新开花粉蛋白的盐酸胍去折叠过程。结果显示：新开花粉蛋白的盐酸胍去折叠是一个只包含天然蛋白和变性终态的二态过程,与已经报道的天花粉蛋白的盐酸胍去折叠的过程不同。