Biomedical subjects

Sanjay K Singh

Publications and source records attributed to Sanjay K Singh.

6 recordsLinked to original sources

PubMed2003

Regioselective enzyme-catalyzed synthesis of sophorolipid esters, amides, and multifunctional monomers.

Novel enzyme-mediated synthetic routes were developed to provide a new family of sophorolipid derivatives and glycolopid-based amphiphilic monomers. These compounds are of great interest for their potential use in immunoregulation, as well as for other biological properties. In the present work, an efficient lipase-catalyzed conversion of sophorolipid ethyl ester to (a) the 6'-monoacylated derivatives using Novozym 435, (b) 6' '-monoacylated derivatives using Lipase PS-C, (c) secondary amide derivatives using Novozym 435, and (d) 6',6' '-diacylated amide derivatives using Novozym 435 in an one-pot reaction and (e) the regioselective monoacylation of an amide derivative at the 6'- and 6' '-positions using Novozym 435 and Lipase PS-C, respectively, are described. The ethyl ester produced by esterification of the sophorolipid mixture with sodium ethoxide was subjected to acylation catalyzed by Novozym 435 in dry tetrahedrofuran (THF) with vinyl acetate and vinyl methacrylate to produce 6'-monoacylated derivatives. In contrast, Lipase PS-C catalyzed acylations of sophorolipid ethyl ester in dry THF with vinyl acetate and vinyl methacrylate to give the corresponding 6'-monoacylated derivatives. Novozym 435 mediated amidation of sophorolipid ethyl ester in dry THF with phenethylamine, tyramine, p-methoxyphenethylamine, 2-(p-tolyl)ethylamine, and p-fluorophenethylamine generated the corresponding secondary amides but not tertiary amides. The formation of diacyl derivatives of amides was achieved by their treatment with vinyl acetate and vinyl methacrylate in dry THF using Novozym 435 as catalyst. The conversion of sophorolipid ethyl ester to the same diacyl derivatives of amide (i.e., both amidation and acylation) in high yield was also demonstrated in dry THF by a one-pot reaction using Novozym 435. Furthermore, regioselective monoacylation of a sophorolipid amide at 6' and 6' ' in dry THF with vinyl acetate and vinyl methacrylate using Novozym 435 and Lipase PS-C was also demonstrated.

Acylation↗

PubMed2003

Synthesis, characterization and in vitro anti-invasive activity screening of polyphenolic and heterocyclic compounds.

Invasion is the hallmark of malignant tumors, and is responsible for the bad prognosis of the untreated cancer patients. The search for anti-invasive treatments led us to screen compounds of different classes for their effect in an assay for invasion. Thirty-nine new compounds synthesized in the present study along with 56 already reported compounds belonging mainly to the classes of lactones, pyrazoles, isoxazoles, coumarins, desoxybenzoins, aromatic ketones, chalcones, chromans, isoflavanones have been tested against organotypic confronting cultures of invasive human MCF-7/6 mammary carcinoma cells with embryonic chick heart fragments in vitro. Three of them (a pyrazole derivative, an isoxazolylcoumarin and a prenylated desoxybenzoin) inhibited invasion at concentrations as low as 1 microM; instead of occupying and replacing the heart tissue within 8 days, the MCF-7/6 cells grew around the heart fragments and left it intact, when treated with these compounds. At the anti-invasive concentration of 1 microM, the three compounds did not affect the growth of the MCF-7/6 cells, as shown in the sulforhodamine B assay. Aggregate formation on agar was not stimulated by any of the three anti-invasive compounds, making an effect on the E-cadherin/catenin complex improbable. This is an invasion suppressor that can be activated in MCF-7/6 cells by a number of other molecules. Our data indicate that some polyphenolic and heterocyclic compounds are anti-invasive without being cytotoxic for the cancer cells.

Antineoplastic Agents↗

PubMed2003

Two reactions of Haloferax volcanii RNA splicing enzymes: joining of exons and circularization of introns.

Archaeal RNA splicing involves at least two protein enzymes, a specific endonuclease and a specific ligase. The endonuclease recognizes and cleaves within a characteristic bulge-helix-bulge (BHB) structure formed by pairing of the regions near the two exon-intron junctions, producing 2',3'-cyclic phosphate and 5'-hydroxyl termini. The ligase joins the exons and converts the cyclic phosphate into junction phosphate. The ligated product contains a seven-base hairpin loop, in which the splice junction is in between the two 3' terminal residues of the loop. Archaeal splicing endonucleases are also involved in rRNA processing, cutting within the BHB structures formed by pairing of the 5' and 3' flanking regions of the rRNAs. Large free introns derived from pre-rRNAs have been observed as stable and abundant circular RNAs in certain Crenarchaeota, a kingdom in the domain Archaea. In the present study, we show that the cells of Haloferax volcanii, a Euryarchaeote, contain circular RNAs formed by 3',5'-phosphodiester linkage between the two termini of the introns derived from their pre-tRNAs. H. volcanii ligase, in vitro, can also circularize both endonuclease-cleaved introns, and non-endonuclease-produced substrates. Exon joining and intron circularization are mechanistically similar ligation reactions that can occur independently. The size of the ligated hairpin loop and position of the splice junction within this loop can be changed in in vitro ligation reactions. Overall, archaeal RNA splicing seems to involve two sets of two symmetric transesterification reactions each.

Exons↗

PubMed2002

Method for efficient fast spin echo Dixon imaging.

In order to satisfy the Carr-Purcell-Meiboom-Gill (CPMG) condition, echo shift as dictated in fast-spin-echo (FSE)-based Dixon imaging was previously achieved by applying a time shift to the readout gradient and the data acquisition window. Accordingly, interecho spacing is increased, which entails increased image blurring and, in multislice imaging, a significant reduction in the slice coverage for a given imaging time. In this work, a new method is developed by which the echo shift is induced by "sandwiching" in time the readout gradient with a pair of small gradients of equal area and of opposite polarity. While data with non-zero phase shifts between water and fat signals are collected as fractional echoes, no increase in echo spacing is necessary with the modified acquisition strategy, and increased time efficiency is therefore achieved. In order to generate separate water-only and fat-only images in data processing, a set of low-resolution images are first reconstructed from the central symmetric portion (either 128 x 128 or 64 x 64) of the acquired multipoint Dixon data. High-resolution images using all the acquired data, including some partial Fourier-reconstructed images, are then phase demodulated using the phase errors determined from the low-resolution images. The feasibility of the technique is demonstrated using a water and fat phantom as well as in clinical patient imaging.

Adipose Tissue↗

PubMed2002

The Willgerodt-Kindler reaction on lupenone: unusual oxidative dimerization.

In continuation of our interest in chemical modification of triterpenoids, the Willgerodt-Kindler reaction of a lupane type triterpenoid lupenone provided a novel dimerized product 2. Formation of 2 is associated with an unusual oxidative dimerization of lupenone under Willgerodt-Kindler reaction conditions. The structure 2 was confirmed by extensive analysis of spectroscopic data including ES-MS and 2D-NMR.

Dimerization↗

PubMed2002

MR imaging of leptomeningeal metastases: comparison of three sequences.

BACKGROUND AND PURPOSE: Recent work has shown that fluid-attenuated inversion recovery (FLAIR) imaging with contrast enhancement is highly sensitive for detecting subarachnoid space disease. We hypothesized that contrast-enhanced FLAIR imaging has superior sensitivity to contrast-enhanced T1-weighted MR imaging in detecting leptomeningeal metastases. METHODS: Sixty-eight patients referred for suspected leptomeningeal metastases underwent 74 MR imaging studies. The patients had either temporally related cytologic proof of leptomeningeal metastases or negative results of clinical follow-up confirming absence of leptomeningeal metastases. The MR imaging examinations included unenhanced and contrast-enhanced FLAIR images and contrast-enhanced T1-weighted MR images that were independently reviewed by two neuroradiologists blinded to the results of cytology. Each of the three sequences was reviewed individually and separately and was assigned a score of positive or negative for leptomeningeal metastases. Discrepancies were settled by consensus. RESULTS: Of the 17 studies of patients with cytology-proven leptomeningeal metastases, two were positive based on unenhanced FLAIR images, seven were positive based on contrast-enhanced FLAIR images, and 10 were positive based on contrast-enhanced T1-weighted MR images. Of the 57 studies of patients without leptomeningeal metastases, 53 were negative based on unenhanced FLAIR images, 50 were negative based on contrast-enhanced FLAIR images, and 53 were negative based on contrast-enhanced T1-weighted MR images. The sensitivity and specificity of unenhanced FLAIR images for detecting leptomeningeal metastases were 12% (two of 17) and 93% (53 of 57), respectively. The sensitivity and specificity for contrast-enhanced FLAIR images for detecting leptomeningeal metastases were 41% (seven of 17) and 88% (50 of 57), respectively. The sensitivity and specificity of contrast-enhanced T1-weighted MR images for detecting leptomeningeal metastases were 59% (10 of 17) and 93% (53 of 57), respectively. CONCLUSION: Contrast-enhanced fast FLAIR sequences are less sensitive than standard contrast-enhanced T1-weighted MR sequences in detecting intracranial neoplastic leptomeningeal disease.

Adolescent↗