Carbonic anhydrase inhibitors. Inhibition of cytosolic isozyme XIII with aromatic and heterocyclic sulfonamides: a novel target for the drug design

Lehtonen, Jonna; Parkkila, Seppo; Vullo, Daniela; Casini, Angela; Scozzafava, Andrea; Supuran, Claudiu T.

doi:10.1016/j.bmcl.2004.04.106

Cited by 38 publications

(39 citation statements)

References 26 publications

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“…While the present study demonstrates variations in intrarenal P t O 2 associated with healthy kidneys in an acute situation, future studies will need to explore changes in tissue PO 2 within chronic disease. The Clark type O 2 electrodes measure O 2 through the consumption of O 2 at the tip of the electrode (11,19,20,25) and are limited by the need for penetration of the kidney capsule; however, they are considered to be a reference standard for assessment of tissue oxygenation (10). Recent advances in polymer biomaterials may offer a promising coating that may improve future sensor biocompatibility.…”

Section: Discussionmentioning

confidence: 99%

Regional decreases in renal oxygenation during graded acute renal arterial stenosis: a case for renal ischemia

Warner

Gomez

Bolterman

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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. Regional decreases in renal oxygenation during graded acute renal arterial stenosis: a case for renal ischemia. Am J Physiol Regul Integr Comp Physiol 296: R67-R71, 2009. First published October 29, 2008 doi:10.1152/ajpregu.90677.2008.-Ischemic nephropathy describes progressive renal failure, defined by significantly reduced glomerular filtration rate, and may be due to renal artery stenosis (RAS), a narrowing of the renal artery. It is unclear whether ischemia is present during RAS since a decrease in renal blood flow (RBF), O 2 delivery, and O2 consumption occurs. The present study tests the hypothesis that despite proportional changes in whole kidney O 2 delivery and consumption, acute progressive RAS leads to decreases in regional renal tissue O 2. Unilateral acute RAS was induced in eight pigs with an extravascular cuff. RBF was measured with an ultrasound flow probe. Cortical and medullary tissue oxygen ͑P t O 2 ͒ of the stenotic kidney was measured continuously with sensors during baseline, three sequentially graded decreases in RBF, and recovery. O 2 consumption decreased proportionally to O2 delivery during the graded stenosis (19 Ϯ 10.8, 48.2 Ϯ 9.1, 58.9 Ϯ 4.7 vs. 15.1 Ϯ 5, 35.4 Ϯ 3.5, 57 Ϯ 2.3%, respectively) while arterial venous O 2 differences were unchanged. Acute RAS produced a sharp reduction in O 2 efficiency for sodium reabsorption (P Ͻ 0.01). Cortical ͑P t O 2 ͒ decreases are exceeded by medullary decreases during stenosis (34.8 Ϯ 1.3%). Decreases in tissue oxygenation, more pronounced in the medulla than the cortex, occur despite proportional reductions in O 2 delivery and consumption. This demonstrates for the first time that hypoxia is present in the early stages of RAS and suggests a role for hypoxia in the pathophysiology of this disease. Furthermore, the notion that arteriovenous shunting and increased stoichiometric energy requirements are potential contributors toward ensuing hypoxia with graded and progressive acute RAS cannot be excluded.ischemia; renal tissue oxygenation; renal blood flow; pig THE TERM "ISCHEMIC NEPHROPATHY" has been used to describe progressive renal failure, defined by a significantly reduced glomerular filtration rate (GFR) or loss of renal parenchyma due to renal artery stenosis, a narrowing of one or more of the renal arteries. Ischemia, however, results from a rate of blood flow that is insufficient to satisfy metabolic demands, thereby leading to tissue hypoxia. There is little evidence to suggest that ischemic nephropathy is accompanied by renal tissue hypoxia (24). In fact, the kidney has a high blood flow relative to its weight (3), which results in very small arterial-venous differences in oxygenation, suggesting a large O 2 supply and limited O 2 consumption. Importantly, Nielsen et al. (15) found in patients with significant unilateral renal artery stenosis that O 2 consumption decreased with limited blood flow, suggesting that a decrease in O 2 supply is not enough to cause ischemic renal disease (22). Moreover, the reduced O 2 supply and demand s...

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Section: Discussionmentioning

confidence: 99%

Regional decreases in renal oxygenation during graded acute renal arterial stenosis: a case for renal ischemia

Warner

Gomez

Bolterman

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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“…However, it is interesting to record here that mCAXIII plays an important role in pH regulation in the reproductive tract of both females and males. Such a potential of mCA is recently recognized 30,31 .…”

Section: Introductionmentioning

confidence: 97%

“…The reasons for such an extensive study being CAs are involved in crucial physiological processes. Consequent to the important role of CAs, their inhibition by carbonic anhydrase inhibitors may be explored for designing useful drugs in the management and prevention of many diseases [20][21][22][23][24][25][26][27][28][29][30][31] . The isozymes mCAXIII, which show a cytosolic sub cellular localization, is one among to 15 isozymes presently known in humans.…”

Section: Introductionmentioning

confidence: 99%

“…Recently Supuran has reported 31 inhibition of mCAXIII with aromatic and heterocyclic sulfonamides. Out of the 32 inhibitors used by Supuran only 14 could be tested for mCA XIII.…”

Section: Introductionmentioning

confidence: 99%

“…This is the main reason to carry out the first QSAR study on mCA XIII inhibitor. In the present study, therefore, we have used mCAXIII data with 14 sulfonamides 30,31 , the structural details of these sulfonamides are given in Table 1. The topological indices, including Balaban and Balaban type indices were used and their calculation was made using DRAGON software 32 .…”

Section: Introductionmentioning

confidence: 99%

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QSAR study on murine recombinant isozyme mCAXIII: topological vs structural descriptors

Singh¹,

Singh²,

Thakur³

et al. 2006

Arkivoc

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The paper describes a first novel QSAR study on murine recombinant isozyme mCAXIII. A comparative study on modeling of inhibition of this isozyme is made using a series of topological, structural descriptors as well as their combinations. The results have shown that distance-based topological indices yield significantly better models than the structural descriptors and the combination of topological and structural descriptors. In all the three cases the Balaban type indices played a dominating role.

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Advances in the Inhibitory and Structural Investigations on Carbonic Anhydrase Isozymes XIII and XV

Hilvo

Simone

Supuran

et al. 2009

Drug Design of Zinc‐Enzyme Inhibitors

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Carbonic anhydrase inhibitors. Inhibition of cytosolic isozyme XIII with aromatic and heterocyclic sulfonamides: a novel target for the drug design

Cited by 38 publications

References 26 publications

Regional decreases in renal oxygenation during graded acute renal arterial stenosis: a case for renal ischemia

Regional decreases in renal oxygenation during graded acute renal arterial stenosis: a case for renal ischemia

QSAR study on murine recombinant isozyme mCAXIII: topological vs structural descriptors

Advances in the Inhibitory and Structural Investigations on Carbonic Anhydrase Isozymes XIII and XV

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