排序方式: 共有60条查询结果,搜索用时 31 毫秒
21.
Wenbin Liu KBS Institute of Mathematics Statistics The University of Kent Canterbury CT NF Engl Wei Gong Ningning Yan LSEC 《计算数学(英文版)》2009,(1):97-114
In this paper, we study numerical methods for an optimal control problem with pointwise state constraints. The traditional approaches often need to deal with the deltasingularity in the dual equation, which causes many difficulties in its theoretical analysis and numerical approximation. In our new approach we reformulate the state-constrained optimal control as a constrained minimization problems only involving the state, whose optimality condition is characterized by a fourth order elliptic variational inequality. Then direct numerical algorithms (nonconforming finite element approximation) are proposed for the inequality, and error estimates of the finite element approximation are derived. Numerical experiments illustrate the effectiveness of the new approach. 相似文献
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Pacchiano F Aggarwal M Avvaru BS Robbins AH Scozzafava A McKenna R Supuran CT 《Chemical communications (Cambridge, England)》2010,46(44):8371-8373
4-Substituted-ureido benzenesulfonamides showing inhibitory activity against carbonic anhydrase (CA, EC 4.2.1.1) II between 3.3-226 nM were crystallized in complex with the enzyme. Hydrophobic interactions between the scaffold of the inhibitors in different hydrophobic pockets of the enzyme were observed, explaining the diverse inhibitory range of these derivatives. 相似文献
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Winum JY Maresca A Carta F Scozzafava A Supuran CT 《Chemical communications (Cambridge, England)》2012,48(66):8177-8179
Pazopanib, a new, multi-targeted tyrosine kinase inhibitor (TKI) used clinically for the treatment of several types of tumors, incorporates a primary sulfonamide moiety normally associated with the inhibition of the metallo enzyme carbonic anhydrase (CA, EC 4.2.1.1). Here we show that pazopanib and related sulfonamides such as indisulam, acetazolamide or ureido-substituted peptidomimetic benzenesulfonamides are low nanomolar inhibitors of many of the fifteen human isoforms hCA I-XIV. These data indicate that in addition to the TK inhibitory action, pazopanib may exert antitumor/antimetastatic effects also due to the potent inhibition of the tumor-associated, hypoxia-inducible enzymes CA IX and XII. 相似文献
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Carta F Aggarwal M Maresca A Scozzafava A McKenna R Supuran CT 《Chemical communications (Cambridge, England)》2012,48(13):1868-1870
The zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1) is inhibited by several classes of zinc-binders (sulfonamides, sulfamates, and sulfamides) as well as by compounds which do not interact with the metal ion (phenols, polyamines and coumarins). Here we report a new class of potent CA inhibitors which bind the zinc ion: the dithiocarbamates (DTCs). They coordinate to the zinc ion from the enzyme active site in monodentate manner and establish many favorable interactions with amino acid residues nearby. Several low nanomolar CA I, II and IX inhibitors were detected. 相似文献
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A Divalent PAMAM‐Based Matrix Metalloproteinase/Carbonic Anhydrase Inhibitor for the Treatment of Dry Eye Syndrome 下载免费PDF全文
V. Baldoneschi Prof. S. Burgalassi Dr. D. Vullo Dr. A. Akdemir Dr. E. Dragoni A. Louka M. Mamusa Dr. D. Monti Prof. D. Berti Prof. E. Novellino Prof. G. De Rosa Prof. C. T. Supuran Prof. C. Nativi 《Chemistry (Weinheim an der Bergstrasse, Germany)》2016,22(5):1714-1721
Synthetic sulfonamide derivatives are a class of potent matrix metalloproteinase inhibitors (MMPI) that have potential for the treatment of diseases related to uncontrolled expression of these enzymes. The lack of selectivity of the large majority of such inhibitors, leading to the inhibition of MMPs in tissues other than the targeted one, has dramatically reduced the therapeutic interest in MMPIs. The recent development of efficient drug delivery systems that allow the transportation of a selected drug to its site of action has opened the way to new perspectives in the use of MMPIs. Here, a PAMAM‐based divalent dendron with two sulfonamidic residues was synthesized. This nanomolar inhibitor binds to the catalytic domain of two MMPs as well as to the transmembrane human carbonic anhydrases (hCAs) XII, which is present in the eye and considered an antiglaucoma target. In the animal model of an experimental dry eye, no occurrence of dotted staining in eyes treated with our inhibitor was observed, indicating no symptoms of corneal desiccation. 相似文献
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A Combined Crystallographic and Theoretical Study Explains the Capability of Carboxylic Acids to Adopt Multiple Binding Modes in the Active Site of Carbonic Anhydrases 下载免费PDF全文
Dr. Katia D'Ambrosio Dr. Melissa D'Ascenzio Dr. Simone Carradori Dr. Simona M. Monti Prof. Claudiu T. Supuran Dr. Giuseppina De Simone 《Chemistry (Weinheim an der Bergstrasse, Germany)》2016,22(1):97-100
Carboxylates are the least investigated class of inhibitors of carbonic anhydrases (CAs). Here we explain the versatility of binding of these molecules to CAs by examining a new adduct of hCA II with N‐carboxymethyl‐saccharin. 相似文献
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Parkkila S Vullo D Maresca A Carta F Scozzafava A Supuran CT 《Chemical communications (Cambridge, England)》2012,48(29):3551-3553
Acetoacetic acid and R-3-hydroxy-butyric acid (BHB) are "ketone bodies", metabolites produced during the ketogenic diet. We discovered that they inhibit in the submicromolar-micromolar range several carbonic anhydrase (CA, EC 4.2.1.1) isoforms involved in relevant physiologic processes such as lipogenesis and tumorigenesis. The BHB fragment is also present in the molecules of most statins, widely used drugs for inhibiting cholesterol biosynthesis through the 3-hydroxy-3-methyl-glutaryl-CoA reductase pathway. Three such statins, atorvastatin, fluvastatin and rosuvastatin, showed submicromolar-low nanomolar inhibition of the fifteen human isoforms hCA I-XIV. Our data point out that in addition to their cholesterol lowering properties, these drugs may exert a therapeutic effect by inhibiting lipogenesis through mitochondrial CA inhibition. The statins are also low nanomolar inhibitors of the tumor-associated isoforms CA IX and XII. Based on the BHB/statin scaffolds, antiepileptic, antiobesity and antitumor compounds with higher affinity for the various CA isoforms involved in epileptogenesis (CA VA, VB, VII), lipogenesis (CA III, CA VA, CA VB) and tumorigenesis (CA IX and CA XII) may be designed. 相似文献
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Felipe Raposo Passos Mansoldo Fabrizio Carta Andrea Angeli Veronica da Silva Cardoso Claudiu T. Supuran Alane Beatriz Vermelho 《Molecules (Basel, Switzerland)》2020,25(22)
Chagas disease still has no effective treatment option for all of its phases despite being discovered more than 100 years ago. The development of commercial drugs has been stagnating since the 1960s, a fact that sheds light on the question of how drug discovery research has progressed and taken advantage of technological advances. Could it be that technological advances have not yet been sufficient to resolve this issue or is there a lack of protocol, validation and standardization of the data generated by different research teams? This work presents an overview of commercial drugs and those that have been evaluated in studies and clinical trials so far. A brief review is made of recent target-based and phenotypic studies based on the search for molecules with anti-Trypanosoma cruzi action. It also discusses how proteochemometric (PCM) modeling and microcrystal electron diffraction (MicroED) can help in the case of the lack of a 3D protein structure; more specifically, Trypanosoma cruzi carbonic anhydrase. 相似文献