Furazan and furoxan sulfonamides are strong α-carbonic anhydrase inhibitors and potential antiglaucoma agents

Chegaev, Konstantin; Lazzarato, Loretta; Tamboli, Yasinalli; Boschi, Donatella; Blangetti, Marco; Scozzafava, Andrea; Carta, Fabrizio; Masini, Emanuela; Fruttero, Roberta; Supuran, Claudiu T.; Gasco, Alberto

doi:10.1016/j.bmc.2014.06.016

Cited by 32 publications

(18 citation statements)

References 27 publications

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“…Phenylsulfonylfuroxan 45 is less selective and possesses strong inhibitory activity against three isoforms (hCA II, IX, and XII). Moreover, hybrids 44 b , c , despite their different inhibitory potential toward hCA II/XII isoforms, showed stronger activity in lowering intraocular pressure than the reference drug dorzolamide …”

Section: Synthesis No‐donor Properties and Pharmacological Activitmentioning

confidence: 98%

“…The nitro group in compound 41 was substituted with phenoxy and phenylsulfonyl moieties, with subsequent oxidation of sulfur in hybrid 42 b to the phenylsulfonyl subunit (Scheme ). Sulfonamide derivatives 42 a – c were found to be strong and selective hCA XII isoform inhibitors, while the inhibitory potential of these structures toward the hCA I, II, and IX isoforms is rather weak …”

Section: Synthesis No‐donor Properties and Pharmacological Activitmentioning

confidence: 99%

“… Synthesis of furoxan sulfonamide hybrids . Reagents and conditions : a) ClSO 3 H, 0 °C, then RT, 4 h, 34 %; b) 32 % NH 3 , THF, RT, 30 min, 67 %; c) PhOH, NaOH, acetone/H 2 O, RT, 6 h, 84 %; d) PhSH, NaOH, acetone/H 2 O, RT, 6 h, 91 %; e) KMnO 4 , AcOH, RT, 85 %.…”

Section: Synthesis No‐donor Properties and Pharmacological Activitmentioning

confidence: 99%

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Molecular Hybridization Tools in the Development of Furoxan‐Based NO‐Donor Prodrugs

Ферштат

Махова

2017

ChemMedChem

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The molecular hybridization of different compounds with known pharmacological activity is a particularly prominent approach for the design of potential drugs with improved pharmacokinetic profiles. Much attention over the last decade has been focused on the synthesis of hybrid structures with a nitric oxide (NO)-donor framework, as NO is a ubiquitous and crucial regulator of cellular metabolism, affecting various physiological and pathophysiological processes. 1,2,5-Oxadiazole 2-oxides (furoxans), which are capable of exogenous NO release in the presence of thiol cofactors, are an important class of prospective NO donors. As such, a wide range of hybrid compounds that combine a furoxan ring with various pharmacologically active structures have been created. This review focuses on recent results in the synthesis and pharmacological activity of furoxan-based hybrids. Special attention is given to chemo- and regioselective methods used in the preparation of these hybrid structures, and the role of synergistic effects on their pharmacological activity, associated with the furoxan fragment.

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Section: Synthesis No‐donor Properties and Pharmacological Activitmentioning

confidence: 98%

Section: Synthesis No‐donor Properties and Pharmacological Activitmentioning

confidence: 99%

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Molecular Hybridization Tools in the Development of Furoxan‐Based NO‐Donor Prodrugs

Ферштат

Махова

2017

ChemMedChem

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“…Up to now, 16 different α‐CA isoenzymes have been identified in human body, which are dissimilar by molecular properties, oligomeric arrangement, cellular localization, distribution tissue and organs, expression levels, kinetic features, and response to different classes of inhibitors . Some of these isozymes are cytosolic (CA I, II, III, VII, and XIII), the others are membrane bound (CA IV, IX, XII, XIV, and XV), two are mitochondrial (CA VA and VB), and one is secreted (CA VI) that has been initially in bovine parotid gland, and then in human saliva and serum . Also, there are not catalytic three isoenzymes (CA VIII, X, and XI), functions of which are not yet fully understood.…”

Section: Introductionmentioning

confidence: 99%

Inhibition properties of some flavonoids on carbonic anhydrase I and II isoenzymes purified from human erythrocytes

Huyut

Beydemır

Gülçın

2017

J Biochem Mol Toxicol

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Carbonic anhydrases (CAs, E.C.4.2.1.1) play a critical role in many important physiological events and treatment of some diseases. Flavonoids or phenolic compounds have been discovered as novel CAs inhibitors instead of the traditional sulfonamides, with different binding to CAs, pro-drug activities, and new inhibition mechanisms. Here, we investigated the inhibition effects of some flavonoids including malvin, callistephin, oenin, pelargonin, silychristin, and 1-(4-methoxyphenyl)-2-methyl-3-nitro-1-H-indol-6-ol (ID-8) against hCA I and II, which purified from human erythrocytes by affinity column chromatography. Both hCA isoenzymes were inhibited by flavonoids, with IC and K values in the range of 2.34 nM to 346.5 μM and 51.01-99.55 μM for hCA I and 86.60-750.00 μM for hCA II, respectively. These results showed that flavonoids especially malvin and oenin effectively inhibited hCA I and II isoenzymes. Hence, they may be used as an effective CA inhibitor in medical applications for treatment of certain diseases such as glaucoma, in the future.

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“…Until now, 16 different a-CA isoenzymes have been identified in various tissues and organs with different expression levels, kinetic and molecular properties, and oligomeric rearrangements as well as various abilities to respond to different inhibitory classes 4,5 . There are 13 catalytic and three acatalytic isoforms of CArelated proteins (CARPs) 6 . According to the known cellular localisation, these isoenzymes are cytosolic (CA I, II, III, VII V and XIII), membrane-bound (CA IV, IX, XII, XIV and XV), mitochondrial (CA VA and VB) and salivary (CA VI) 7 .…”

Section: Introductionmentioning

confidence: 99%

Inhibitory effects of some phenolic compounds on the activities of carbonic anhydrase: fromin vivotoex vivo

Huyut

Beydemır

Gülçın

2015

Journal of Enzyme Inhibition and Medicinal Chemistry

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Carbonic anhydrase (CA) inhibitors have been used for more than 60 years for therapeutic purposes in many diseases table such as in medications against antiglaucoma and as diuretics. Phenolic compounds are a new class of CA inhibitor. In our study, we tested the effects of arachidonoyl dopamine, 2,4,6-trihydroxybenzaldehyde and 3,4-dihydroxy-5-methoxybenzoic acid on esterase and the CO 2 -hydratase activities of CA I and II isozymes purified from in vivo to ex vivo. The K i values of arachidonoyl dopamine, 2,4,6-trihydroxybenzaldehyde and 3,4-dihydroxy-5-methoxybenzoic acid were 203.80, 1170.00 and 910.00 mM, respectively for hCA I and 75.25, 354.00 and 1510.00 mM, respectively for hCA II. Additionally, IC 50 values from in vivo studies were found to be in the range of 173.25-1360.0 mM for CA I and II, respectively, using CO 2 -hydratase activity methods. These results demonstrated that phenolic compounds used in in vivo studies could be used in different biomedical applications to inhibit approximately 30% of the CO 2 -hydratase activity of the total CA enzyme of rat erythrocytes.

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Furazan and furoxan sulfonamides are strong α-carbonic anhydrase inhibitors and potential antiglaucoma agents

Cited by 32 publications

References 27 publications

Molecular Hybridization Tools in the Development of Furoxan‐Based NO‐Donor Prodrugs

Molecular Hybridization Tools in the Development of Furoxan‐Based NO‐Donor Prodrugs

Inhibition properties of some flavonoids on carbonic anhydrase I and II isoenzymes purified from human erythrocytes

Inhibitory effects of some phenolic compounds on the activities of carbonic anhydrase: fromin vivotoex vivo

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