Arylazopyrazole-Based Photoswitchable Inhibitors Selective for Escherichia coli Dihydrofolate Reductase.

Selective inhibitors of Escherichia coli dihydrofolate reductase (eDHFR) are crucial chemical biology tools that have widespread clinical applications. We developed a set of eDHFR-selective photoswitchable inhibitors by derivatizing the structure of our previously reported methotrexate (MTX) azolog, azoMTX. Substitution of the skeletal p-phenylene group of azoMTX with bulky bis-alkylated arylazopyrazole moieties significantly increased its selectivity toward eDHFR over human DHFR. Owing to the physical properties of arylazopyrazoles, the new ligands exhibited nearly complete Z-to-E photoconversion and high thermostability of Z-isomers. In addition, real-time photoreversible control of eDHFR activity was achieved by alternatively switching the illumination light wavelengths.

Consumption of H2S from Our Daily Diet: Determination by a Simple Chemosensing Method.

A unique method has been developed for comparative analysis of H2S produced from food samples from our daily diet, both qualitatively and quantitatively. The selective detection of H2S has been executed by introducing a simple chemodosimeter (PN-N 3 ) that gives response on the basis of intramolecular charge transfer. UV-vis, fluorimetric, and NMR titrations were performed to demonstrate the sensing mechanism and electronic environment of PN-N 3 in the presence of H2S. Density functional theory calculations were performed to validate the mechanism of azide (PN-N 3 ) reduction to amine (PN-NH 2 ) by the strong reducing power of H2S. The potentiality of this chemosensing method is that it could be treated as a simple, less-time-consuming, and cost-effective method for determining H2S in biological samples in the nanomolar range.

Serum metabolomics of Indian women with polycystic ovary syndrome using 1H NMR coupled with a pattern recognition approach.

Polycystic ovary syndrome (PCOS) is one of the most commonly occurring metabolic and endocrinological disorders affecting women of reproductive age. Metabolomics is an emerging field that holds promise in understanding disease pathophysiology. Recently, a few metabolomics based studies have been attempted in PCOS patients; however, none of them have included patients from the Indian population. The main objective of this study was to investigate the serum metabolomic profile of Indian women with PCOS and compare them with controls. Proton nuclear magnetic resonance (1H NMR) was used to first identify the differentially expressed metabolites among women with PCOS from the Eastern region of India during the discovery phase and further validated in a separate cohort of PCOS and control subjects. Multivariate analysis of the binned spectra indicated 16 dysregulated bins in the sera of these women with PCOS. Out of these 16 bins, 13 identified bins corresponded to 12 metabolites including 8 amino acids and 4 energy metabolites. Amongst the amino acids, alanine, valine, leucine and threonine and amongst the energy metabolites, lactate and acetate were observed to be significantly up-regulated in women with PCOS when compared with controls. The remaining 4 amino acids, l-glutamine, proline, glutamate and histidine were down-regulated along with 2 energy metabolites: glucose and 3-hydroxybutyric acid. Our findings showed dysregulations in the expression of different metabolites in the serum of women with PCOS suggesting the involvement of multiple pathways including amino acid metabolism, carbohydrate/lipid metabolism, purine and pyrimidine metabolism and protein synthesis.