Murat Çelik

N-Acylsulfonamides strongly inhibit human carbonic anhydrase isoenzymes I and II.

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.

9,10-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.

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.

Synthesis and Chemistry of Endoperoxides Derived from 3,4-Dihydroazulen-1(2H)-one: An Entry to Cyclopentane-Anellated Tropone Derivatives

Reduction of trienone 1 and subsequent treatment with acid in MeOH furnished 1-methoxy-1,2,3,4-tetrahydroazulene (13). Photo-oxygenation of 13 provided the two bicyclic endoperoxides 14 and 15. Pyrolysis of 14 and 15 gave the corresponding bis-epoxides 17 and 18, which have been synthesized also upon treatment with a catalytic amount of CoTPP (TPP=tetraphenylporphyrin). That an unusual endoperoxide-endoperoxide rearrangement has not been observed strongly supports the assumption that the carbonyl group in 2 – 4 is responsible for this unprecedented endoperoxide-endoperoxide rearrangement. Treatment of the endoperoxides 14 and 15 with a catalytic amount of Et3N at 0° provided the azulenones 22 and 23 in high yield. Attempted cleavage of the O−O peroxide linkage in 14 and 15 with thiourea resulted, contrary to our expectation, in the formation of 22 and 23. That thiourea acts as a base instead of a reducing reagent has been observed for the first time in peroxide chemistry.

The human carbonic anhydrase isoenzymes I and II inhibitory effects of some hydroperoxides, alcohols, and acetates

Abstract The carbonic anhydrases (CAs, EC 4.2.1.1) represent a superfamily of widespread enzymes, which catalyze a crucial biochemical reaction, the reversible hydration of carbon dioxide to bicarbonate and protons. Human CA isoenzymes I and II (hCA I and hCA II) are ubiquitous cytosolic isoforms. In this study, a series of hydroperoxides, alcohols, and acetates were tested for the inhibition of the cytosolic hCA I and II isoenzymes. These compounds inhibited both hCA isozymes in the low nanomolar ranges. These compounds were good hCA I inhibitors (Kis in the range of 24.93–97.99 nM) and hCA II inhibitors (Kis in the range of 26.04–68.56 nM) compared to acetazolamide as CA inhibitor (Ki: 34.50 nM for hCA I and Ki: 28.93 nM for hCA II).

Synthesis of a new class of aminocyclitol analogues with the conduramine D-2 configuration.

Summary A new class of aminocyclitol derivatives with the bicyclo[4.2.0]octane skeleton was synthesized starting from cyclooctatetraene. Photooxygenation of trans-7,8-diacetoxy- and cis-7,8-dichlorobicyclo[4.2.0]octa-2,4-diene afforded the bicyclic endoperoxides. Reduction of the latter with thiourea followed by a Pd(0) catalyzed ionization/cyclization reaction gave the corresponding oxazolidinone derivatives. Oxidation of the double bond with KMnO4 or OsO4 followed by acetylation gave the acetate derivatives, the exact configuration of which was determined by spectroscopic methods. Hydrolysis of the oxazolidinone rings and removal of the acetate groups furnished the desired aminocyclitols.

Intermolecular amination of allylic and benzylic alcohols leads to effective inhibitions of acetylcholinesterase enzyme and carbonic anhydrase I and II isoenzymes

In this study, we aimed to determine the inhibition effects of novel synthesized sulfamates (2a–g), sulfonamides (3b–f), carbonyl sulfonamides (3h and i), and carbonyl sulfamates (4h and 4i), which were tested against two human cytosolic carbonic anhydrase I and II isozymes (hCA I and II) and acetylcholinesterase (AChE) enzyme. For inhibition properties of allylic sulfamates, the half maximal inhibitory concentration (IC50) and inhibition constant (Ki) were calculated for each novel compounds. The allylic sulfamates showed that Ki values are in the range of 187.33–510.31 pM for hCA I, 104.22–290.09 pM against hCA II, and 12.73–103.63 pM against AChE. The results demonstrated that all newly synthesized compounds had shown effective inhibition against hCA I and II isoenzymes and AChE enzyme.

Novel sulfamate derivatives of menthol: Synthesis, characterization, and cholinesterases and carbonic anhydrase enzymes inhibition properties

Sulfamates have a large spectrum of biological activities including enzyme inhibition. Eight sulfamates derived from menthol (2a–h) were synthesized. Also, in the other section of this study, novel sulfamate derivatives of menthol were tested against some metabolic enzymes including acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and carbonic anhydrase I and II enzymes (hCAs I and II). The newly synthesized novel menthol sulfamate and menthol carbonyl sulfamate derivatives showed Ki values in the range of 34.37 ± 8.17 to 53.40 ± 10.61 nM against hCA I, 12.91 ± 4.57 to 38.67 ± 6.22 nM against hCA II, 111.17 ± 52.36 to 522.86 ± 120.08 nM against AChE, and 50.01 ± 11.73 to 109.63 ± 50.08 nM against BChE. As a result, the novel menthol sulfamate and menthol carbonyl sulfamate derivatives can be promising Alzheimers disease drug candidates and novel hCA I and hCA II enzymes inhibitors.

Synthesis of 4-hydroxy-4-methylcyclohex-2-en-1-one

4-Hydroxy-4-methylcyclohex-2-en-1-one was synthesised from 4-methylanisole. The key step is the regioselective reaction of singlet oxygen with 4-methylcyclohex-3-en-1-one.