Design, synthesis, and biological evaluation of novel (1-thioxo-1,2,3,4-tetrahydro-β-carbolin-9-yl)acetic acids as selective inhibitors for AKR1B1.

New substituted (1-thioxo-1,2,3,4-tetrahydro-β-carbolin-9-yl)acetic acids were designed as the inhibitor of AKR1B1 based upon the structure of rhetsinine, a minor alkaloidal component of Evodia rutaecarpa, and twenty derivatives were synthesized and evaluated. The most active compound of the series was (2-benzyl-6-methoxy-1-thioxo-1,2,3,4-tetrahydro-β-carbolin-9-yl)acetic acid (7m), which showed comparable inhibitory activity for AKR1B1 (IC(50)=0.15μM) with clinically used epalrestat (IC(50)=0.

6,7-Dihydroxy-4-phenylcoumarin as inhibitor of aldose reductase 2.

We report the structure-activity relationship of a series of coumarins as aldose reductase 2 (ALR2) inhibitors and their suppressive effect on the accumulation of galactitol in the rat lens. We evaluated their ALR2 selectivity profile against sorbitol dehydrogenase and aldehyde reductase (ALR1). Our study revealed that substitutions in the C7 OH group enhanced the potency toward ALR2, while the C6 OH group interferes with ALR1 inhibition activity.

Analysis of amino acid sequences of penicillin-binding protein 2 in clinical isolates of Neisseria gonorrhoeae with reduced susceptibility to cefixime and ceftriaxone.

Neisseria gonorrhoeae strains with reduced susceptibility to cefixime and ceftriaxone, with minimum inhibitory concentrations (MICs) of cefixime of 0.125-0.25 microg/ml and ceftriaxone of 0.

In silico approach to identify the expression of the undiscovered molecules from microarray public database: identification of odorant receptors expressed in non-olfactory tissues.

Although both genomic sequencing and expression analysis are becoming indispensable for biological research, methods that can effectively survey large public gene expression repositories remain to be established. In this study, we developed an approach for the retrieval of tissue-specific expression information for certain genes from public databases; our approach was based on performance of a basic local alignment search tool search against probes on DNA microarray chips. To test the effectiveness of this approach, we examined the expression of human odorant receptors in non-olfactory tissues, as recent studies showed that such non-olfactory odorant receptors have physiological and pathophysiological significance.