Gülşah Çelik

Salen and tetrahydrosalen derivatives act as effective inhibitors of the tumor-associated carbonic anhydrase XII—A new scaffold for designing isoform-selective inhibitors

Salen and tetrahydrosalen derivatives possess metal-chelating properties and have been used as ligands in organic synthesis and as scaffolds for developing therapeutic agents. Fourteen such compounds were synthesized in order to explore their ability to inhibit the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1). Human (h) isoforms hCA I, hCA II, hCA IX and hCA XII were included in the investigation. Several aliphatic and aromatic spacers were introduced between the two chelating groups from salen/tetrahydrosalen in order to explore a diverse chemical space for designing CA inhibitors, which incorporate both phenol and polyamine fragments in their molecule. Some of these compounds showed CA inhibitory activity in the low micromolar-nanomolar range and a pronounced selectivity for inhibiting an isoform over-expressed in hypoxic tumors, hCA XII, over hCA I, II and IX.

4-Functionalized 1,3-diarylpyrazoles bearing benzenesulfonamide moiety as selective potent inhibitors of the tumor associated carbonic anhydrase isoforms IX and XII.

A library of 4-functionalized 1,3-diarylpyrazoles (3a-3h, 5a-5g and 6a-6g) was designed, synthesized and evaluated against four human carbonic anhydrase (CA, EC 4.2.1.1) isozymes representing two cytosolic isozymes hCA I and hCA II, and two transmembrane tumor associated ones, hCA IX and hCA XII. All the twenty two tested compounds exhibited excellent CA activity profile against the four CA isozymes when compared to the reference drug acetazolamide. Six of the tested compounds (3a-3b, 3f, 3h, 6a and 6b) displayed low nanomolar affinity (Ki < 5 nM) for hCA IX whereas seven compounds (3a-3b, 3d-3f, 3h and 6f) displayed Ki < 10 nM against hCA XII. In addition, they acted as selective CA inhibitors of isoforms IX and XII over the physiological isoforms I and II.

Benzenesulfonamide bearing 1,2,4-triazole scaffolds as potent inhibitors of tumor associated carbonic anhydrase isoforms hCA IX and hCA XII.

Three series of novel heterocyclic compounds (3a-3g, 4a-4g and 5a-5g) containing benzenesulfonamide moiety and incorporating a 1,2,4-triazole ring, have been synthesized and investigated as inhibitors against four isomers of the α-class carbonic anhydrases (CAs, EC 4.2.1.1), comprising hCAs I and II (cytosolic, ubiquitous isozymes) and hCAs IX and XII (transmembrane, tumor associated isozymes). Against the human isozymes hCA I and II, compounds of two series (3a-3g and 4a-4g) showed Ki values in the range of 84-868 nM and 5.6-390 nM, respectively whereas compounds of series 5a-5g were found to be poor inhibitors (Ki values exceeding 10,000 nM in some cases). Against hCA IX and XII, all the tested compounds exhibited excellent to moderate inhibitory potential with Ki values in the range of 2.8-431 nM and 1.3-63 nM, respectively. Compounds 3d, 3f and 4f exhibited excellent inhibitory potential against all of the four isozymes hCA I, II, IX and XII, even better than the standard drug acetazolamide (AZA) whereas compound of the series 5a-5g were comparatively less potent but more selective towards hCA IX and XII.

Differential in vitro inhibition studies of some cerium vanadate derivatives on xanthine oxidase

Abstract In this preliminary study, a new series of some cerium vanadate derivatives have been investigated as new type of inhibitors of xanthine oxidase (XO; E.C 1.17.3.2). XO is a superoxide-producing enzyme found normally in serum and the lungs, and its activity is concerned with several important health problems such as gout, severe liver damage, vascular dysfunction and injury, oxidative eye injury and renal failure. In this study, we present a critical overview of the effects of these novel type agents on XO with comparing the efficacy and safety profiles of allopurinol, the efficient classical inhibitor of XO.

Fast microwave synthesis and characterization of MgTi2O5

Abstract Magnesium dititanate, MgTi2O5 was obtained via a microwave synthesis method. Powder X-ray diffraction, infrared spectroscopy and thermogravimetric/differantial thermal analysis measurements have been used to characterize the sample.

Hydrothermal Synthesis and Characterization of non‐Linear Optic Potassium Pentaborate(KB5)

Alkali metal borates having outstanding pyhsical properties have drawn much concern, both theoretically and experimentally. Potassium pentaborate stands out of such borates owing to usage of non‐linear optics(NLO) [1]. The reason why the alkali metal borates display non‐linear optical properties is the various coordination possibilities of boron atom [2]. In addition to NLO properties, KB5 can be also used as a film to prevent oxidation, cover fluxes, flame retardant and inhibition of cements [3]. KB5 can be synthesized more easily than the common NLO materials ADP and KDP [4,5]. A number of research articles have been published in the literature discussing the growth and NLO properties of KB5 crystals [6–10]. We synthesized potassium pentaborate tetrahydrate (ICDD: 25‐624) by hydrothermal method in a short time using KOH and H3BO3 as raw materials. The synthesized material was characterization by powder X‐ray powder diffraction (XRD), fourier transform infrared spectroscopy (FTIR) and thermo gravimetric/...