Sürdürülebilir Kalkınma Amaçları
Yayınlar
- MakaleAçık Erişim20169,10-Dibromo-N-aryl-9,10-dihydro-9,10-[3,4]epipyrroloanthracene-12,14-diones: Synthesis and Investigation of Their Effects on Carbonic Anhydrase Isozymes I, II, IX, and XII
Göksu, Haydar; Topal, Meryem; Keskin, Ali; Gültekin, Mehmet S.; Çelik, Murat; Gülçin, Ilhami; Tanc, Muhammet; Supuran, Claudiu T.
N-substituted maleimides were synthesized from maleic anhydride and primary amines. 1,4-Dibromo-dibenzo[e,h]bicyclo-[2,2,2]octane-2,3-dicarboximide derivatives (4a-f) were prepared by the [4+2] cycloaddition reaction of dibromoanthracenes with the N-substituted maleimide derivatives. The carbonic anhydrase (CA, EC 4.2.1.1) inhibitory effects of the new derivatives were assayed against the human (h) isozymes hCA I, II, IX, and XII. All tested bicyclo dicarboximide derivatives exhibited excellent inhibitory effects in the nanomolar range, with Ki values in the range of 117.73-232.87 nM against hCA I and of 69.74-111.51 nM against hCA II, whereas they were low micromolar inhibitors against hCA IX and XII. A series of 9,10-dibromo-N-aryl-9,10-dihydro-9,10-[3,4]epipyrroloanthracene-12,14-diones (4a-f) were synthesized from N-substituted maleimide derivatives and 9,10-dibromoanthracene. Compounds 4a-f were assayed against human carbonic anhydrases (hCA) IX and XII, which are the two tumor-associated isozymes, and hCA I and II, which represent the most common off-targets for the development of selective anticancer CA inhibitors.
- MakaleAçık Erişim2016Investigation of the inhibitory properties of some phenolic standards and bee products against human carbonic anhydrase I and II
Aygul, Imdat; Yaylaci Karahalil, Fatma; Supuran, Claudiu T.
Polyphenols are important secondary products of plants with the potential to inhibit carbonic anhydrases. The aim of this study was to investigate the inhibition effects of various phenolic standards, honey, propolis, and pollen species on human carbonic anhydrase I and II. The inhibition values (IC50) of the phenolics (gallic acid, protocatechuic acid, quercetin, catechin, tannic acid, and chrysin) ranged from 0.009 to 0.32 μg/mL, tannic acid emerging as the best inhibitor. The inhibition values of three different types of honey, heather, rhododendron, and chestnut ranged between 2.32 and 25.10 μg/mL, the chestnut honeys exhibiting the best inhibition. The ethanolic extracts of pollen and propolis exhibited good inhibitory properties, with IC50 values between 0.486 and 3.320 μg/mL. In order to evaluate the phenolic composition of bee products, phenolic profiles and total phenolic contents (TFC) were also measured. The inhibition ranking among the natural products studied was phenolic standards > propolis > pollen > honeys, and inhibition was related to TFC.
- MakaleAçık Erişim2016Acetylcholinesterase and carbonic anhydrase isoenzymes I and II inhibition profiles of taxifolin
Gocer, Hulya; Topal, Fevzi; Topal, Meryem; Küçük, Murat; Teke, Dilek; Gülçin, Ilhami; Alwasel, Saleh H.; Supuran, Claudiu T.
Taxifolin, also known as dihydroquercetin, is a flavonoid commonly found in plants. Carbonic anhydrase (CA, EC 4.2.1.1) plays an important role in many critical physiological events including carbon dioxide (CO2)/bicarbonate (HCO3-) respiration and pH regulation. There are 16 known CA isoforms in humans, of which human hCA isoenzymes I and II (hCA I and II) are ubiquitous cytosolic isoforms. In this study, the inhibition properties of taxifolin against the slow cytosolic isoenzyme hCA I, and the ubiquitous and dominant rapid cytosolic isoenzyme hCA II were studied. Taxifolin, as a naturally bioactive flavonoid, has a K-i of 29.2nM against hCA I, and 24.2nM against hCA II. For acetylcholinesterase enzyme (AChE) inhibition, K-i parameter of taxifolin was determined to be 16.7nM. These results clearly show that taxifolin inhibited both CA isoenzymes and AChE at the nM levels.
- MakaleAçık Erişim2015N-Acylsulfonamides strongly inhibit human carbonic anhydrase isoenzymes i and II
Yildirim, Alper; Atmaca, Ufuk; Keskin, Ali; Topal, Meryem; Çelik, Murat; Gülçin, Ilhami; Supuran, Claudiu T.
Sulfonamides represent a significant class of biologically active compounds that inhibit carbonic anhydrase (CA, EC.: 4.2.1.1) isoenzymes involved in different pathological and physiological events. Sulfonamide CA inhibitors are used therapeutically as diuretic, antiglaucoma, antiobesity and anticancer agents. A series of new sulfonamides were synthesized using imides and tosyl chloride as starting materials. These N-acylsulfonamides efficiently inhibited the cytosolic human carbonic anhydrase isoenzymes I, and II (hCA I, and II), with nanomolar range inhibition constants ranging between 36.4 ± 6.0-254.6 ± 18.0 and 58.3 ± 0.6-273.3 ± 2.5 nM, respectively.
- MakaleAçık Erişim2014Oxidation of cyanobenzocycloheptatrienes: Synthesis, photooxygenation reaction and carbonic anhydrase isoenzymes inhibition properties of some new benzotropone derivatives
Güney, Murat; Coskun, Ahmet; Topal, Fevzi; Dastan, Arif; Gülçin, Ilhami; Supuran, Claudiu T.
The oxidation of some cyanocycloheptatrienes with CrO3 and pyridine was investigated and a few new nitrile functionalised benzotropone derivatives were obtained. Photooxygenation reaction of these products was also studied. The structures of the formed products were determined on the basis of NMR spectroscopy and the formation mechanism of unusual products was discussed. Human carbonic anhydrase isoenzymes I, and II (hCA I and hCA II) inhibition properties of nitrile functionalized new benzotropone derivatives were also studied. Both CA isozymes were inhibited in the low micromolar range by these nitrile functionalized benzotropone analogues. The newly synthesized benzotropone derivatives showed inhibition constants in the sub-micromolar range (2.51-4.06 mu M). The best hCA I inhibition was observed in 5H-benzocycloheptene-7-carbonitrile (K-1: 2.88 +/- 0.86 mu M). On the other hand, 5-oxo-5H-benzocycloheptatriene-7-carbonitrile showed the powerful inhibitory effect against hCA II (K-i: 2.51 +/- 0.34 mu M). (C) 2014 Elsevier Ltd. All rights reserved.
- MakaleAçık Erişim2011In vitro inhibition of α-carbonic anhydrase isozymes by some phenolic compounds
Öztürk Sarikaya, Sevim Beyza; Topal, Fevzi; Şentürk, Murat; Gülin, Ihami; Supuran, Claudiu T.
Carbonic anhydrase inhibitors (CAIs) are a class of pharmaceuticals used as antiglaucoma agents, diuretics, antiepileptics, in the management of mountain sickness, gastric and duodenal ulcers, neurological disorders or osteoporosis. We report here the inhibitory capacities of some phenolic compounds against three human CA isozymes (hCA I, hCA II, and hCA VI) and the gill carbonic anhydrase of the teleost fish Dicentrarchus labrax (European seabass) (dCA). The isozymes showed quite diverse inhibition profiles with these compounds. These data may lead to design novel CAIs with a diverse inhibition mechanism compared to sulfonamide/sulfamate inhibitors.