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 Erişim2016Antioxidant, antiradical, and anticholinergic properties of cynarin purified from the Illyrian thistle (Onopordum illyricum L.)
Topal, Meryem; Gocer, Hulya; Topal, Fevzi; Kalin, Pinar; Köse, Leyla Polat; Gulçin, Ilhami; Çakmak, Kader C.; Küçük, Murat; Durmaz, Lokman; Gören, Ahmet C.
Cynarin is a derivative of hydroxycinnamic acid and it has biologically active functional groups constituent of some plants and food. We elucidated the antioxidant activity of cynarin by using different in vitro condition bioanalytical antioxidant assays like DMPD•+, ABTS•+, DPPH• and H2O2 scavenging effects, the total antioxidant influence, reducing capabilities, Fe2+ chelating and anticholinergic activities. Cynarin demonstrated 87.72% inhibition of linoleic acid lipid peroxidation at 30 g/mL concentration. Conversely, some standard antioxidants like trolox, tocopherol, butylated hydroxytoluene (BHT), and butylated hydroxyanisole (BHA) exhibited inhibitions of 90.32, 75.26, 97.61, 87.30%, and opponent peroxidation of linoleic acid emulsion at the identical concentration, seriatim. Also, cynarin exhibited effective DMPD•+, ABTS•+, DPPH•, and H2O2 scavenging effects, reducing capabilities and Fe2+ chelating effects. On the contrary, IC50 and Ki parameters of cynarin for acetylcholinesterase enzyme inhibition were determined as 243.67 nM (r2: 0.9444) and 39.34 ± 13.88 nM, respectively. This study clearly showed that cynarin had marked antioxidant, anticholinergic, reducing ability, radical-scavenging, and metal-binding activities.
- 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.