Browsing by Author "Supuran, Claudiu T."

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Evaluation of the Anticancer Potential of a Sulphonamide Carbonic Anhydrase Ix Inhibitor on Cervical Cancer Cells
(Taylor & Francis Ltd, 2019) Koyuncu, Ismail; Tuluce, Yasin; Qadir, Hewa Slahaddin; Durgun, Mustafa; Supuran, Claudiu T.
Cervical cancer is a common type of cancer. Carbonic anhydrase IX (CA IX) is an attractive target for tumour therapy, being overexpressed in many cancers. We investigated the anticancer properties of the aromatic sulphonamide S-1 as a CA IX inhibitor on cervical cancer cells (HeLa) positive for CA IX expression and normal prostate epithelial cell line (PNT1-A) negative for CA IX. We examined the cytotoxic, apoptosis, genotoxic, and oxidative stress activity of S-1 on HeLa and PNT1-A cell lines. S-1 induced significant reduction of cell viability, caused apoptosis, and up-regulated ROS production. This decrease in cell survival rate can be attributed to the high level of ROS and apoptosis, which has also been shown to arrest the cell cycle. Our findings indicated that S-1 is more effective on HeLa than PNT1-A. S-1 was able to induce apoptosis of cervical cancer cells and is a possible candidate for future anticancer studies.
Rosmarinic Acid Inhibits Some Metabolic Enzymes Including Glutathione S-Transferase, Lactoperoxidase, Acetylcholinesterase, Butyrylcholinesterase and Carbonic Anhydrase Isoenzymes
(Taylor & Francis Ltd, 2016) Gulcin, Ilhami; Scozzafava, Andrea; Supuran, Claudiu T.; Koksal, Zeynep; Turkan, Fikret; Cetinkaya, Songul; Alwasel, Saleh H.
Rosmarinic acid (RA) is a natural polyphenol contained in many aromatic plants with promising biological activities. Carbonic anhydrases (CAs, EC 4.2.1.1) are widespread and intensively studied metalloenzymes present in higher vertebrates. Acetylcholinesterase (AChE, E.C. 3.1.1.7) is intimately associated with the normal neurotransmission by catalysing the hydrolysis of acetylcholine to acetate and choline and acts in combination with butyrylcholinesterase (BChE) to remove acetylcholine from the synaptic cleft. Lactoperoxidase (LPO) is an enzyme involved in fighting pathogenic microorganisms, whereas glutathione S-transferases (GSTs) are dimeric proteins present both in prokaryotic and in eukaryotic organisms and involved in cellular detoxification mechanisms. In the present study, the inhibition effects of rosmarinic acid on tumour-associated carbonic anhydrase IX and XII isoenzymes, AChE, BChE, LPO and GST enzymes were evaluated. Rosmarinic acid inhibited these enzymes with K(i)s in the range between micromolar to picomolar. The best inhibitory effect of rosmarinic acid was observed against both AChE and BChE.
Synthesis and Biological Evaluation of Aminomethyl and Alkoxymethyl Derivatives as Carbonic Anhydrase, Acetylcholinesterase and Butyrylcholinesterase Inhibitors
(Taylor & Francis Ltd, 2017) Gulcin, Ilhami; Abbasova, Malahat; Taslimi, Parham; Huyut, Zubeyir; Safarova, Leyla; Sujayev, Afsun; Supuran, Claudiu T.
Compounds containing nitrogen and sulfur atoms can be widely used in various fields such as industry, medicine, biotechnology and chemical technology. Therefore, the reactions of aminomethylation and alkoxymethylation of mercaptobenzothiazole, mercaptobenzoxazole and 2-aminothiazole were developed. Additionally, the alkoxymethyl derivatives of mercaptobenzoxazole and 2-aminothiazole were synthesized by a reaction with hemiformals, which are prepared by the reaction of alcohols and formaldehyde. In this study, the inhibitory effects of these molecules were investigated against acetylcholinesterase (AChE), butyrylcholinesterase (BChE) enzymes and carbonic anhydrase I, and II isoenzymes (hCA I and II). Both hCA isoenzymes were significantly inhibited by the recently synthesized molecules, with Ki values in the range of 58-157 nM for hCA I, and 81-215 nM for hCA II. Additionally, the Ki parameters of these molecules for BChE and AChE were calculated in the ranges 23-88 and 18-78 nM, respectively.