Aryl sulfonamides are a widely used drug class for the inhibition of carbonic anhydrases. In the context of our program of photochromic pharmacophores we were interested in the exploration of azobenzene-containing sulfonamides to block the catalytic activity of human carbonic anhydrase II (hCAII). Herein, we report the synthesis and in vitro evaluation of a small library of nine photochromic su...

Ever since my days as a graduate student in Berkeley, John Edsall provided a model for scientific rigor. In the 1960s, the authoritative volume by Edsall and Wyman, Biopyhsical Chemistry, was one of the rare books that covered a wide range of the topics of interest in this discipline, and its authors took on the aura of founding fathers. In addition, my thesis adviser, Howard Schachman, often r...

The oxidation of some cyanocycloheptatrienes with CrO3 and pyridine was investigated and a few new nitrile functionalised benzotropone derivatives were obtained. Photooxygenation reaction of these products was also studied. The structures of the formed products were determined on the basis of NMR spectroscopy and the formation mechanism of unusual products was discussed. Human carbonic anhydras...

Cu(II) complexes of 1-[4-(3-ethyl-piperidine-2,6-dione)-3-yl]-phenyl-2,4,6-trisubstituted pyridinium perchlorates, containing alkyl, aryl and combinations of these two types of moieties in their molecule were synthesized and characterized by elemental analysis, spectroscopy, magnetic, thermogravimetric and conductimetric measurements. In these complexes, Cu(II) ions are in octahedral geometry w...

A series of ethylene bis-imidazoles was synthesized via a novel microwave-mediated synthesis. Biological testing on eight isozymes of carbonic anhydrase (CA) present in the human brain revealed compounds with nanomolar potency against CA VA and CA VII, also displaying excellent selectivity against other CA isozymes present in this organ.

CO2 H2O^ HCO3 H (Eq. 1) The first carbonic anhydrase was purified from erythrocytes in 1933 (1) followed by the characterization of several mammalian isozymes that dominated research on carbonic anhydrase until recently. Although it has been known since the 1940s that carbonic anhydrase is ubiquitous in plants (2), where it is essential for CO2 fixation, relatively few studies had been reported...

Thiazide diuretics are widely used to treat hypertension, but their use is associated with impaired glucose tolerance. We propose that the diabetogenic action of thiazides may be due to their ability to open calcium-activated potassium (KCa) channels in pancreatic beta-cells.

Inhibition of renal carbonic anhydrase reduces proximal reabsorption and activates tubuloglomerular feedback (TGF). The TGF response is saturable, with highest gain focused near the natural flow rate. Therefore, any large change imposed on ambient tubular flow should reduce the TGF response to subequent flow perturbations. However, TGF tends to align with ambient flow regardless of the rate of ...

The aim of this study was to investigate the relationship between several parameters of saliva and erosive wear in adolescents. (Un-)stimulated saliva was collected from 88 adolescents with erosion and 49 controls (age 16 ± 1 years). Flow rate, pH and buffer capacity were determined immediately. Total protein content, carbonic anhydrase VI, amylase, albumin, calcium, phosphate, urea, sodium, ch...

Cells of a high CO(2)-requiring mutant (E(1)) and wild type of Synechococcus PCC7942 were incubated with COS in the light, then suspended in COS-free medium and their CO(2) exchange was measured using an open gas-analysis system under the conditions where photosynthetic CO(2) fixation is inhibited. When the suspension of cells untreated with COS was illuminated, the rate of CO(2) uptake was hig...