Carbonic anhydrase inhibitors: Inhibition of the human transmembrane isozyme XIV with a library of aromatic/heterocyclic sulfonamides

Ozensoy, Ozen; Nishimori, Isao; Vullo, Daniela; Puccetti, Luca; Scozzafava, Andrea; Supuran, Claudiu T.

doi:10.1016/j.bmc.2005.06.022

Cited by 22 publications

(13 citation statements)

References 35 publications

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“…pH and Carbon Dioxide Concentration. CA has showed the excellent performance at neutral pH (Supuran et al 1999;Özensoy et al 2005;Innocenti et al 2009). Reports indicated that the carbon dioxide conversion to bicarbonate ions using CA as catalyst is a strong pH depending reaction process due to the pH effect on the activity of CA (Trachtenberg and Bao 2005).…”

Section: Carbon Dioxide Sequestrationmentioning

confidence: 98%

Carbon Capture and Storage

2015

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is a leading geoscientist of his generation, venture capitalist, and a significant figure in the politics of Colorado. In this article he reviews some inconvenient truths about the timely implementation of CCS projects in the US, some of which may resonate in other countries seeking CO 2 reduction measures.T he greatest challenge to carbon capture and storage (CCS) is likely to be economic rather than technical. A September 2008 McKinsey report estimated that the first commercial scale CCS projects, potentially to be built soon after 2020, would cost €35-50 per metric ton of CO 2 abated. They assume that if 500+ projects were built by 2030, the cost might fall to €25-40 per ton. About two-thirds of that cost is for CO 2 capture.It is interesting to consider those costs on a global scale. A study by Pacala and Socolow implies that we need to cut a cumulative 25 Gton of CO 2 over the next 50 years just to cap the CO 2 concentration in the atmosphere at a modest 500 ppm (we are now at 390 ppm). If all of our solutions cost €25 per ton, the economic impact would be €625 billion ($833 billion) over the next 50 years.Reducing CO 2 is a global issue, but the US creates 20% of the problem. It also offers an interesting case study on the difficulty of finding practical solutions in a challenging political and economic environment. Hopefully along the way the reader will discover opportunities as well as pitfalls to avoid.According to the US Department of Energy's Energy Information Administration (DOE-EIA), 98% of America's human-generated CO 2 comes from energy use, with 40% of that from electricity (coal and natural gas) and 33% from transportation (mostly petroleum). Coal produces 45% of America's electricity and natural gas produces 23% (see Figure 1).McKinsey's study notes that 'Retrofitting of existing power plants is likely to be more expensive than new installations, and economically feasible only for relatively new plants (with high efficiencies).' But according to the DOE-EIA, over the past 20 years coal contributed only 3.7% of total added US capacity while natural gas accounted for 88%. Few modern, efficient US coal plants have been added in the past 20 years.'Efficiency' is a term used to define the conversion of the theoretical energy content of a fuel into electricity. The McKinsey report notes that the energy required for the CCS CO 2 capture process increases the amount of coal that must be burned per MW-hour delivered, and estimates a CCS 'efficiency penalty' of 10%. This means that if a future coal plant could be built to achieve a 50% thermal efficiency, CCS would decrease that efficiency to 40%. Such a plant would be burning 50/40=1.25 times as much coal per MW-hour. And burning 25% more coal would also increase harmful emissions since CCS captures only about 90% of CO 2 and none of the other pollutants.CCS also faces storage challenges, such as site selection, CO 2 transportation costs, pipeline and CCS site permits, and uncertainties in monitoring CO 2 sequestration. Leakage of just 0.5% per year w...

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Section: Carbon Dioxide Sequestrationmentioning

confidence: 98%

Carbon Capture and Storage

2015

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“…Because CA XIII is an active isozyme predominantly expressed in salivary glands, kidney, brain, lung, gut, uterus and testis, where it probably plays an important role in pH regulation, it was concluded that its inhibition by sulfonamides may lead to novel therapeutic applications for this class of pharmacological agents [43]. The inhibition of the last human isozyme (hCA XIV) discovered up until now has been investigated for the first time with a series of sulfonamides, including the clinically used derivatives mentioned above (but also including zonisamide 16), as well as the sulfamate topiramate 9 [44,45]. The full-length hCA XIV was showed to be an enzyme with a medium-low catalytic activity, quite similar to that of hCA XII, with the following kinetic parameters at 20°C and pH 7.5, for the CO 2 hydration reaction: k cat = 3.12 x 10 5 s -1 and k cat /K M = 3.9 x 10 7 M -1 s -1 .…”

Section: Sulfonamide Sulfamate and Sulfamide Inhibitorsmentioning

confidence: 98%

“…Thus, a large variety of such compounds were either tested for the first time for inhibition of isoforms not investigated up until now (e.g., for example, hCA IV, hCA VB, hCA VII, hCA XII, mCA XIII, hCA XIV and some of the β-or γ-class enzymes [39][40][41][42][43][44][45][46]) or they were designed de novo in the search of compounds with special properties or with selectivity/specificity for some physiologically relevant isozymes, such as CA II, VA, VB, VII, IX, XII, XIII and XIV).…”

Section: Sulfonamide Sulfamate and Sulfamide Inhibitorsmentioning

confidence: 99%

Carbonic anhydrase inhibitors and activators and their use in therapy

Scozzafava¹,

Mastrolorenzo

Supuran³

2006

Expert Opinion on Therapeutic Patents

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“…Except topiramate and zonisamide that exhibited low inhibitory properties (micromolar range), as well as dichlorophenamide that showed a K I of 345 nM against hCA XIV, all other compounds tested showed similar inhibitory potency with low-nanomolar K I for this isozyme ranging from 24 to 43 nM (Table 12.3). The same group reported in 2005 an inhibition study with a library of aromatic and heteroaromatic sulfonamides (19). Among all the investigated compounds, we just report here the most active ones for the inhibition of hCA XIV with inhibition constants of the same order of magnitude as the clinically used drugs 12.1-12.6 ( Figure 12.3).…”

Section: Inhibition Of Hca XIVmentioning

confidence: 94%

Carbonic Anhydrase XIV: Structure, Functions, and Potential Medical Applications

Winum

2015

Carbonic Anhydrases as Biocatalysts

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Carbonic anhydrase inhibitors: Inhibition of the human transmembrane isozyme XIV with a library of aromatic/heterocyclic sulfonamides

Cited by 22 publications

References 35 publications

Carbon Capture and Storage

Carbon Capture and Storage

Carbonic anhydrase inhibitors and activators and their use in therapy

Carbonic Anhydrase XIV: Structure, Functions, and Potential Medical Applications

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