Synthesis and carbonic anhydrase inhibitory effects of new N-glycosylsulfonamides incorporating the phenol moiety.

Published on Aug 15, 2016in Bioorganic & Medicinal Chemistry Letters2.823
· DOI :10.1016/J.BMCL.2016.07.015
Leonardo Ezequiel Riafrecha7
Estimated H-index: 7
(UNLP: National University of La Plata),
Silvia Bua21
Estimated H-index: 21
(UniFI: University of Florence)
+ 1 AuthorsPedro A. Colinas15
Estimated H-index: 15
(UNLP: National University of La Plata)
Sources
Abstract
A small series of N-glycosylsulfonamides incorporating the phenol moiety has been prepared by Ferrier sulfonamidoglycosylation of d-glycals. N-Glycosides were tested for the inhibition of four isoforms of carbonic anhydrase. In this study, all compounds showed good inhibitory activity against hCA I and II, with selectivity against the cytosolic hCA II versus the tumor associated isozymes. These results confirm that attaching carbohydrate moieties to CA phenol pharmacophore improves and enhances its inhibitory activity.
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References24
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#1Anastasia Karioti (A.U.Th.: Aristotle University of Thessaloniki)H-Index: 29
#2Mariangela Ceruso (UniFI: University of Florence)H-Index: 28
Last. Claudiu T. Supuran (UniFI: University of Florence)H-Index: 155
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Carbonic anhydrases (CAs, EC 4.2.1.1) catalyze the fundamental reaction of CO2 hydration in all living organisms, being actively involved in the regulation of a plethora of patho/physiological conditions. They represent a typical example of enzyme convergent evolution, as six genetically unrelated families of such enzymes were described so far. The need to find selective CA inhibitors (CAIs) triggered the investigation of natural product libraries, which proved to be a valid source of agents wit...
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#1Joanna Ombouma (ENSCM: École nationale supérieure de chimie de Montpellier)H-Index: 5
#2Daniella Vullo (UniFI: University of Florence)H-Index: 8
Last. Jean-Yves Winum (ENSCM: École nationale supérieure de chimie de Montpellier)H-Index: 54
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A general approach for the synthesis of carbonic anhydrases glycoinhibitors belonging to an aminoxysulfonamide series is presented using a Ferrier sulfonamidoglycosylation reaction on glycals. All the compounds showed good in vitro inhibitory activity against four human carbonic anhydrase isoforms, with selectivity against the cytosolic (hCA II) vs the tumor associated (hCA IX and XII) enzymes.
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Introduction: The η-class of carbonic anhydrases (CAs, EC 4.2.1.1) was recently discovered as the sixth genetic family of this metalloenzyme superfamily, and seems to be present only in various Plasmodium species, the malaria-provoking pathogens. The present review through detailed biochemical, kinetic and phylogenetic studies afford a clear view regarding the differences between η- and the other CA families.Areas covered: In this review, the authors underlined as the η-CAs, like α-, γ- and δ-cl...
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#1Leonardo Ezequiel Riafrecha (UNLP: National University of La Plata)H-Index: 7
#2Daniela Vullo (UniFI: University of Florence)H-Index: 69
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Fil: Riafrecha, Leonardo Ezequiel. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Quimica. Laboratorio de Estudio de Compuestos Organicos; Argentina
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Abstract Ferrier sulfamidoglycosylation of glycals catalyzed by nitrosonium tetrafluoroborate allowed the preparation of hydroxysulfamide glycosides in good yields with a good α stereoselectivity. A variety of mono-saccharide derivatives was synthesized using this new methodology leading to selective and powerful glycoinhibitors of the tumor associated carbonic anhydrases (CA, EC 4.2.1.1) isoforms CA IX and CA XII.
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#1John L. MagnaniH-Index: 1
Complex carbohydrates contain dense structural information that is decoded in recognition processes among cells, their pathogens and products, as well as many other functional proteins and represent a new source of novel therapeutics. Native carbohydrate ligands, however, lack classic drug-like properties and in general suffer from poor pharmacokinetics, bioavailability, stability, and low affinity. One solution is to rationally design glycomimetic drugs based on the bioactive conformation of th...
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Introduction: Obesity is ranked as one of the top 10 global health problems and the major concern deriving from it is the exposure of the population to a vast array of chronic pathologies such as cardiovascular and musculoskeletal disorders, type 2 diabetes, cancer, such as colon, breast and endometrial cancer, together with psychological disorders derived from this condition. The discovery that the clinically used anticonvulsants topiramate (TPM) and zonisamide (ZNS) induced weight loss in obes...
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#1Fabrizio Carta (UniFI: University of Florence)H-Index: 52
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Introduction: The benzothiadiazines and high ceiling diuretics (hydrochlorothiazide, hydroflumethiazide, quinethazone, metolazone, chlorthalidone, indapamide, furosemide and bumetanide) contain primary sulfamoyl moieties acting as zinc-binding groups in the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). These drugs are widely used clinically and were recently shown to weakly inhibit isoforms CA I and II, but to possess stronger activity against isoforms involved in other important pathologie...
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Abstract We obtained a series of novel N-(2-iodo-2,3-dideoxy-2-en-glycopyranosides)-sulfonamides via the Aza-Ferrier rearrangement of protected-2-iodoglycals in good yields and high stereoselectivity. Their structure and conformation features were determined by NMR. Moreover, we report here the first in detail structure analysis by X-ray diffraction techniques of a 2-iodo-pseudoglycal.
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Carbonic anhydrases (CAs, EC 4.2.1.1) are widely distributed metalloenzymes in both prokaryotes and eukaryotes. They efficiently catalyze the reversible hydration of carbon dioxide to bicarbonate and H+ ions and play a crucial role in regulating many physiological processes. CAs are well-studied drug target for various disorders such as glaucoma, epilepsy, sleep apnea, and high altitude sickness. In the past decades, a large category of diverse families of CA inhibitors (CAIs) have been develope...
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ABSTRACTIntroduction: The enzyme carbonic anhydrase (CA, EC 4.2.1.1) is found in numerous organisms across the tree of life, with seven distinct classes known to date. CA inhibition can be exploited for the treatment of edema, glaucoma, seizures, obesity, cancer and infectious diseases. A myriad of CA inhibitor (CAI) classes and inhibition mechanisms have been identified over the past decade, mainly through structure-based drug design approaches. Five different CA inhibition mechanisms are prese...
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