Murat Güney

Oxidation of cyanobenzocycloheptatrienes: Synthesis, photooxygenation reaction and carbonic anhydrase isoenzymes inhibition properties of some new benzotropone derivatives.

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 (2.51-4.06μM). The best hCA I inhibition was observed in 5H-benzocycloheptene-7-carbonitrile (Ki: 2.88±0.86μM). On the other hand, 5-oxo-5H-benzocycloheptatriene-7-carbonitrile showed the powerful inhibitory effect against hCA II (Ki: 2.51±0.34μM).

Simple methanesulfonates are hydrolyzed by the sulfatase carbonic anhydrase activity

The possible sulfatase activity of several carbonic anhydrase (CA, EC 4.2.1.1) isoforms have been investigated with a series of synthesized methanesulfonate derivatives of phenols. Four α-CA isozymes, i.e. hCA I, hCA II, hCA IV and hCA VI (h = human isoform), were included in the study. We evidenced that the original sulfonate esters are being hydrolyzed effectively to the corresponding phenols which there after act as CA inhibitors. The KI-s of these compounds ranged from 10.24 to 4012 µM against hCA I, 0.10 to 35.42 µM against hCA II, 0.49 to 45.06 µM against hCA IV and 3.27 to 608 µM against CA VI, respectively. The relevant sulfatase activity of CA with these esters is amazing considering the fact that 4-nitrophenyl-sulfate, an activated ester, is not a substrate of these enzymes.

Novel eugenol derivatives: Potent acetylcholinesterase and carbonic anhydrase inhibitors

Eugenol was used as starting material to obtain some phenolic compounds. The synthesis of these phenolic compounds was performed in a two-step procedure. The structures of the formed products (novel eugenol derivatives 1-6) have been determined on the basis of NMR spectroscopy and other spectroscopic methods. The compounds were tested in terms of carbonic anhydrase (CA) inhibition potency. Carbonic anhydrases (CAs, EC 4.2.1.1) are metalloenzymes, which catalyse the reaction between carbon dioxide (CO2) and water (H2O), to generate bicarbonate (HCO3-) and protons (H+). CO2, HCO3- and H+ are essential molecules and ions for many important physiologic processes occurring in all living organisms. Acetylcholinesterase (AChE, E.C.3.1.1.7) is found in high concentrations in the red blood cells and brain. Novel eugenol derivatives (1-6) were tested for the inhibition of two cytosolic CA isoforms I, and II (hCA I, and II) and AChE. These compounds demonstrated effective inhibitory profiles with Ki values in ranging of 113.48-738.69nM against hCA I, 92.35-530.81nM against hCA II, and 90.10-379.57nM against AChE, respectively. On the other hand, acetazolamide clinically used as CA inhibitor, shoed Ki value of 594.11nM against hCA I, and 120.68nM against hCA II, respectively. Also, AChE was inhibited by tacrine as an AChE inhibitor at the 71.18nM level.

Synthesis and carbonic anhydrase inhibitory properties of novel uracil derivatives.

Carbonic anhydrase (CA) inhibitors are valuable molecules based on several therapeutic applications, including antiglaucoma activity. In the present study, inhibition of two human cytosolic carbonic anhydrase isozymes I and II with some uracil derivatives (3-9) were investigated. Compounds 3-9 showed KI values in the range of 10.83-464 μM for hCA I and of 28.88-778.5 μM against hCA II, respectively. Kinetic investigations showed that similarly to classical CA inhibitors, all investigated natural compounds act as competitive inhibitors with 4-NPA as substrate. Uracil derivatives investigated here are promising agents which may be used as lead molecules in order to derivative novel carbonic anhydrase inhibitors that might be useful in medical applications.

Low and high temperature bromination of 2,3-dicarbomethoxy and 2,3-dicyano benzobarrelene: unexpected substituent effect on bromination

The bromination of 2,3-dicarbomethoxy benzobarrelene yielded the dibromide regio- and stereospecifically arising from the aryl shift where the bromine exclusively attacks the double bond from the exo face of the double bond. High temperature bromination of this compound yielded aryl-shift products. From the low temperature bromination of 2,3-dicyano benzobarrelene, non-rearranged products were obtained along with the rearranged products. Surprisingly, we observed that the yield of non-rearranged products decreased on increasing the temperature. A possible role of the substituent was discussed using DFT calculations on model compounds.

Synthesis and Diels-Alder cycloaddition reaction of norbornadiene and benzonorbornadiene dimers

Summary Dimeric forms of norbornadiene and benzonorbornadiene were synthesized starting with known monobromide derivatives. The Diels–Alder cycloaddition reaction of dimers with TCNE and PTAD was investigated and new norbornenoid polycyclics were obtained. All compounds were characterized properly using NMR spectroscopy.

Effects of aryl methanesulfonate derivatives on acetylcholinesterase and butyrylcholinesterase: ZILBEYAZ et al.

There is a dire need for new treatments for Alzheimers disease (AD). Principal drugs have reached maturity, and the number of people affected by AD is growing at a rapid rate. After years of research and many clinical trials, only symptomatic treatments are available. An effective disease‐modifying drug for AD needs to be discovered. The research presented in this paper aims to facilitate in the discovery of new potential targets that could help in the ongoing AD research. Aryl methanesulfonate derivatives were screened for their acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities. IC50 values between 0.660 and 3.397 µM against AChE and 0.885 and 2.596 µM against BuChE were obtained.

Biological evaluation of some uracil derivatives as potent glutathione reductase inhibitors

Discovery of glutathione reductase (GR) inhibitors has become very popular recently due to antimalarial and anticancer activities. In this study, GR inhibitory capacities of some uracil derivatives (UDCs) (1-4) were reported. Some commercially available molecules (5-6) were also tested for comparison reasons. The novel UDCs were obtained in high yields using simple chemical procedures and exhibited much potent inhibitory activities against GR at low nanomolar concentrations with IC50 values ranging from 2.68 to 166.6 nM as compared with well-known agents.