Paving the way to conformationally unravel complex glycopeptide antibiotics by means of Raman optical activity

It is crucial for fundamental physical chemistry techniques to find their application in tackling real-world challenges. Hitherto, Raman optical activity (ROA) spectroscopy is one of the examples where a promising future within the pharmaceutical sector is foreseen, but has not yet been established. Namely, the technique is believed to be able to contribute in investigating the conformational behaviour of drug candidates. We, herein, strive towards the alignment of the ROA analysis outcome and the pharmaceutical expectations by proposing a fresh strategy that ensures a more complete, reliable, and transferable ROA study. The strategy consists of the treatment of the conformational space by means of a principal component analysis (PCA) and a clustering algorithm, succeeded by a thorough ROA spectral analysis and a novel way of estimating the contributions of the different chemical fragments to the total ROA spectral intensities. Here, vancomycin, an antibiotic glycopeptide, has been treated; it is the first antibiotic glycopeptide studied by means of ROA and is a challenging compound in ROA terms. By applying our approach we discover that ROA is capable of independently identifying the correct conformation of vancomycin in aqueous solution. In addition, we have a clear idea of what ROA can and cannot tell us regarding glycopeptides. Finally, the glycopeptide class turns out to be a spectroscopically curious case, as its spectral responses are unlike the typical ROA spectral responses of peptides and carbohydrates. This preludes future ROA studies of this intriguing molecular class.

Raman optical activity tackles the complex conformational space of glycopeptide antibiotics.     

Novel Indole‐Quinazolinone Based Amides as Cytotoxic Agents

Indole‐quinazolinone hybrids with active amides were synthesized, characterized, and assessed for their cytotoxicity. Two molecules displayed substantial activity in sulphorhodamine B assay method.     

New Report of Triterpenoid Betulinic Acid along with Oleanolic Acid from Achyranthes aspera by Reversed-Phase—Ultra Flow Liquid Chromatographic Analysis and Confirmation Using High-Performance Thin-Layer Chromatographic and Fourier Transform—Infrared Spectroscopic Techniques

JPC – Journal of Planar Chromatography – Modern TLC - Triterpenoid betulinic acid (BA) was detected, quantified, and reported for the first time from leaf extract of Achyranthes aspera...     

New Catalysts for Asymmetric Oxidation of Prochiral Sulfides Based on Vanadium Complexes with Levopimaric Acid Derivatives

Kinetics and Catalysis - The formation of vanadium complexes with synthesized enantio- and diastereomerically pure polydentate tetrahydrosalicylidene ligands of the diterpene series was studied...     

On the decay process of turbulence at large Reynolds and Peclet numbers

When fluctuating temperature field is considered to be super imposed on a general field of eddy turbulence, the early period decay phenomena in regard to velocity, temperature and velocity-temperature are guided by three dynamical equations that are obtained here in a straightforward manner. The equations so obtained are simplified for the case of homogeneous turbulence and subsequently for the case of homogeneous and isotropic turbulence.     

In vivo anticancer and histopathology studies of Schiff bases on Ehrlich ascitic carcinoma cells: 1st Cancer Update

Three Schiff bases in two different concentrations were evaluated for their anti-tumor activity against Ehrlich ascites carcinoma (EAC) bearing Swiss albino mice. The in vivo anti-tumor potency of Schiff bases was assessed by measuring the increase in mean survival time of the drug treated over untreated control mice and treated standard (cisplatin) mice. Their toxicity was assessed in vivo in normal, standard, and EAC-bearing mice by measuring the drug-induced changes in biochemical as well as hematological parameters. The histopathology studies to assess the toxicity of these compounds on vital organs also have been studied. Among the three Schiff bases studied, 4-({[3-(4-fluorophenyl)-1H-pyrazol-4-yl]methylene}amino)-5-[(2-methylphenoxy)methyl]-1,2,4-triazole-3-thiol (SB-3) at an optimal dose of 100 mg/kg body weight was found to enhance the mean survival time of infected mice. Deviated hematological parameters and mean survival time in tumor bearing mice were found to be significantly restored towards normal after treatment with SB-3 100 mg/kg body weight of mice. The ALP and SGOT values were found to approach the normal range. A:G ratios also did not deviate from normal on treatment with SB-3. The histopathology studies revealed only mild hepatotoxicity and nephrotoxicity when compared to the normal and standard. The splenic cellularity also did not show much variation from normal. SB-3 at a prime dose of 100 mg has shown promising anticancer activity in vivo against EAC when compared to standard drug with minimum toxic effects.     

A design of an inexpensive demountableX-ray tube

An inexpensive and simple demountable X-ray source, having facilities to excite X-rays either by bombardment of a target by electrons or by fluorescence, has been developed using a stainless steel chamber having six ports. A cathode assembly from a burnt out sealed off Machlett X-ray tube was carefully removed and reused in the present set-up after replacing the filament. A conventional vacuum system consisting of a rotary and diffusion pumps has been utilized for evacuating the chamber. The set-up can be conveniently utilized to carry out X-ray emission spectroscopic work.     

Subjective and objective verifications of the inverse functions of binaural room impulse responses

The binaural room impulse responses (BRIRs) can be applied to 3-D sound field reconstruction, virtual reality, noise control, et al. Because the BRIRs are non-minimum phase functions, it is difficult to find the exact inverse functions of the BRIRs, especially when there are two or more sources in a reverberant space. In this work, a method was proposed to find the inverse functions of BRIRs with two sound sources in a reverberant space. The concept of time delays and the method of weighted least squares were used to find the causal, however, approximate inverse functions. The accuracy of the inverse functions was first evaluated objectively by a dummy head system. The result shows that the distortion due to crosstalk and room reverberation can be improved by 16∼18 dB. The inverse functions were also verified subjectively by 20 students. The result of subjective evaluation also shows that the inverse functions can be used successfully to reduce the crosstalk effect and the room reverberation.     

Deuteron and triton production with high energy sulphur and lead beams

Proton and deuteron production has been observed in S+S and S+Pb collisions at 200 AGeV and in Pb+Pb reactions at 158 AGeV at the CERN SPS accelerator. For Pb+Pb triton production was also measured. The p and d spectra as well as the p and t spectra were observed in similar rapidity ranges and over similar ranges of transverse momenta per nucleon, making it possible to interpret the cross sections of the composite particles in terms of coalescence mechanisms. Volumes of homogeneity were extracted and compared to pion-pair HBT interferometry results. Special attention is given to the dependence on transverse mass, centrality and rapidity. Received: 23 July 2001 / Revised version: 16 November 2001 / Published online: 25 January 2002     

Feature extraction using molecular planes for fuzzy relational clustering of a flexible dopamine reuptake inhibitor

Six rigid-body parameters (Shift, Slide, Rise, Tilt, Roll, Twist) are commonly used to describe the relative displacement and orientation of successive base pairs in a nucleic acid structure. The present work adapts this approach to describe the relative displacement and orientation of any two planes in an arbitrary molecule-specifically, planes which contain important pharmacophore elements. Relevant code from the 3DNA software package (Nucleic Acids Res. 2003, 31, 5108-5121) was generalized to treat molecular fragments other than DNA bases as input for the calculation of the corresponding rigid-body (or "planes") parameters. These parameters were used to construct feature vectors for a fuzzy relational clustering study of over 700 conformations of a flexible analogue of the dopamine reuptake inhibitor, GBR 12909. Several cluster validity measures were used to determine the optimal number of clusters. Translational (Shift, Slide, Rise) rather than rotational (Tilt, Roll, Twist) features dominate clustering based on planes that are relatively far apart, whereas both types of features are important to clustering when the pair of planes are close by. This approach was able to classify the data set of molecular conformations into groups and to identify representative conformers for use as template conformers in future Comparative Molecular Field Analysis studies of GBR 12909 analogues. The advantage of using the planes parameters, rather than the combination of atomic coordinates and angles between molecular planes used in our previous fuzzy relational clustering of the same data set (J. Chem. Inf. Model. 2005, 45, 610-623), is that the present clustering results are independent of molecular superposition and the technique is able to identify clusters in the molecule considered as a whole. This approach is easily generalizable to any two planes in any molecule.