Discovery of a Potent (4 R,5 S)-4-Fluoro-5-methylproline Sulfonamide Transient Receptor Potential Ankyrin 1 Antagonist and Its Methylene Phosphate Prodrug Guided by Molecular Modeling.

Transient receptor potential ankyrin 1 (TRPA1) is a non-selective cation channel expressed in sensory neurons where it functions as an irritant sensor for a plethora of electrophilic compounds and is implicated in pain, itch, and respiratory disease. To study its function in various disease contexts, we sought to identify novel, potent, and selective small-molecule TRPA1 antagonists. Herein we describe the evolution of an N-isopropylglycine sulfonamide lead (1) to a novel and potent (4 R,5 S)-4-fluoro-5-methylproline sulfonamide series of inhibitors.

First report of Rahnella aquatilis infection in crucian carp Carassius auratus in China.

Rahnella aquatilis infection is rare in aquaculture. Here, a Gram-negative rod-shaped bacterium was isolated from diseased crucian carp Carassius auratus in Xuzhou City, Jiangsu Province, eastern China. The isolate was tentatively named strain KCL-5, and subsequently identified as R.

[Two-Dimensional Hetero-Spectral Near-Infrared and Mid-Infrared Correlation Spectroscopy for Discrimination Adulterated Milk].

New approach for discriminant analysis of adulterated milk is proposed based on combining hetero-spectral two-dimensional (2D) near-infrared (NIR) and mid-infrared (IR) correlation spectroscopy along with multi-way partial least squares discriminant analysis (NPLS-DA). Firstly, 36 pure milk samples were collected and 36 adulterated milk with starch samples (0.01 to 1 g · L(-1)) were prepared by adding appropriate mass of starch into pure milk.

Multi-substituted N-phenyl-2, 2-dichloroacetamide analogues as anti-cancer drugs: design, synthesis and biological evaluation.

Our earlier research has shown that mono-substituted N-phenyl-2, 2-dichloroacetamide exhibited much higher anti-cancer activity than the lead compound sodium dichloroacetate (DCA). In this paper, a variety of multi-substituted N-phenyl-2, 2-dichloroacetamides were synthesized and biologically evaluated. The results showed that 3, 5-disubstituted N-phenyl-2, 2-dichloroacetamide analogues had satisfactory potency.

[Raman imaging based on morphological model for human breast cancer tissues].

Raman Mapping spectra were collected on the samples of the normal human breast duct epithelia and the infiltrating duct carcinoma with the excitation wavelength of 633 nm and fitted with the morphological model which was presented before by the author. The normalized coefficients were calculated and used to make Raman images. Examining these images, the authors find that they show quite clearly the distribution of the chemicals which the basis spectrum was mainly derived from and that the DNA coefficient image also indicates the positions and scales of the cell nucleus, while the bright DNA area is bigger and brighter for the infiltrating duct carcinoma than for the normal breast dust epithelia, suggesting the cell nucleus in cancer tissue are larger than those in normal tissue.

Protolimonoids from Melia toosendan.

Toosendanone A (1), a new euphane (tirucallane)-type triterpene bearing a five-membered ring in the side chain and the first cyclopentanyl protolimonoid, was isolated from the bark of Melia toosendan, along with two new tirucallanes, toosendanic acids A (2) and B (3). The structure and absolute configuration of compound 1 was elucidated by spectroscopic data interpretation and X-ray diffraction analysis. Compounds 1-3 were evaluated for cytotoxicity against a small panel of cancer cell lines.

3D-QSAR studies of boron-containing dipeptides as proteasome inhibitors with CoMFA and CoMSIA methods.

Three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were performed for a series of dipeptide boronate proteasome inhibitors using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) techniques. A training set containing 46 molecules served to establish the models. The optimum CoMFA and CoMSIA models obtained for the training set were all statistically significant with cross-validated coefficients (q(2)) of 0.

[Study on Raman linear model of human breast tissue].

A linear regression model for Raman spectra of human breast tissue was developed with 10 basis spectra which were derived from the spectra of fat, cell cytoplasm, collagen, beta-carotene, DNA and cholesterol etc. This model was tested statistically with more than 2 000 spectra collected from both normal and tumor breast tissue samples. The confidence of F-test for the model significance was 1 to all the spectra and the average of multiple determination coefficients measuring the fit goodness was 0.

Characterization and expression analysis of Paralichthys olivaceus voltage-dependent anion channel (VDAC) gene in response to virus infection.

Voltage-dependent anion channel (VDAC, also known as mitochondrial porin) is acknowledged to play an important role in stress-induced mammalian apoptosis. In this study, Paralichthys olivaceus VDAC (PoVDAC) gene was identified as a virally induced gene from Scophthalmus Maximus Rhabdovirus (SMRV)-infected flounder embryonic cells (FEC). The full length of PoVDAC cDNA is 1380 bp with an open reading frame of 852 bp encoding a 283 amino acid protein.

3D-QSAR study of 20 (S)-camptothecin analogs.

Aim: To build up a quantitative structure-activity relationship (QSAR) model of 20 (S)-camptothecin (CPT) analogs for the prediction of the activity of new CPT analogs for drug design.

Methods: A training set of 43 structurally diverse CPT analogs which were inhibitors of topoisomerase I were used to construct a quantitative structure-activity relationship model with a comparative molecular field analysis (CoMFA). The QSAR model was optimized using partial least squares (PLS) analysis.

Molecular characterisation and inductive expression of a fish protein arginine methyltransferase 1 gene in response to virus infection.

Protein arginine methyltransferase 1 (PRMT1) is currently thought as an effector to regulate interferon (IFN) signalling. Here Paralichthys olivaceus PRMT1 (PoPRMT1) gene was identified as a virally induced gene from UV-inactivated Scophthalmus maximus Rhabdovirus (SMRV)-infected flounder embryonic cells (FEC). PoPMRT1 encodes a 341-amino-acid protein that shares the conserved domains including post-I, motif I, II and III.

[Exploring relationship between traditional effects of traditional Chinese medicine and modern pharmacological activities by "co-effect compounds"].

The compound that distributes in the herbs with one common effect was named as "co-effect compound" (CEC). The CECs of three traditional Chinese medicine(TCM) effects, purgative, relieving pain and clearing heat, had been found and studied. A strong corresponding relationship was found between the pharmacological activities of CECs and the TCM effect they belong to.