Synthesis of novel bis-sulfone derivatives and their inhibition properties on some metabolic enzymes including carbonic anhydrase, acetylcholinesterase, and butyrylcholinesterase.

In this study, a series of novel bis-sulfone compounds (2a-2j) were synthesized by oxidation of the bis-sulfides under mild reaction conditions. The bis-sulfone derivatives were characterized by 1 H-NMR, 13 C-NMR, Fourier-transform infrared spectroscopy, and elemental analysis techniques. Nuclear Overhauser effect experiments were performed to determine the orientation of the sulfonyl groups in bis-sulfone derivatives. Here, we report the synthesis and testing of novel bis-sulfone compound-based hybrid scaffold of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors for the development of novel molecules toward the therapy of Alzheimer's disease. The novel synthesized bis-sulfone compounds demonstrated Ki values between 11.4 ± 3.4 and 70.7 ± 23.2 nM on human carbonic anhydrase I isozyme (hCA I), 28.7 ± 6.6 to 77.6 ± 5.6 nM on human carbonic anhydrase II isozyme (hCA II), 18.7 ± 2.61 to 95.4 ± 25.52 nM on AChE, and 9.5 ± 2.1 to 95.5 ± 1.2 nM on BChE enzymes. The results showed that novel bis-sulfone derivatives can have promising drug potential for glaucoma, leukemia, epilepsy, and Alzheimer's disease, which are associated with the high enzymatic activity of hCA I, hCA II, AChE, and BChE enzymes.

Monodisperse Ag/Pd core/shell nanoparticles assembled on reduced graphene oxide as highly efficient catalysts for the transfer hydrogenation of nitroarenes.

Addressed herein is a facile seed-mediated synthesis of Ag/Pd core/shell nanoparticles (NPs) and their assembly on reduced graphene oxide (rGO) to catalyze the transfer hydrogenation of nitroarenes to anilines using ammonia borane (AB) as a hydrogen donor under ambient conditions. Monodisperse Ag/Pd core/shell NPs with controllable Pd shell-thickness were synthesized by the means of thermal decomposition of palladium(II) bromide over as-prepared Ag NPs in the mixture of oleylamine and oleic acid at 220°C. As-synthesized Ag/Pd core/shell NPs were characterized by TEM, HR-TEM, XRD, XPS, UV-Vis spectroscopy and ICP-MS and then they were assembled on reduced graphene oxide (rGO). Next, rGO@Ag/Pd catalysts were tested in the transfer hydrogenation of nitroarenes in which ammonia borane (AB) was used as a hydrogen donor at room temperature. It was demonstrated that the thickness of the Pd shell has a significant effect on the catalytic activity of rGO@Ag/Pd catalysts and the 1.75nm Pd shell provided the highest performance in the transfer hydrogenation reactions. The rGO@Ag/Pd catalyzed transfer hydrogenation reactions were tested over a variety of nitroarenes (total 16 examples) and they were all converted to the corresponding aniline derivatives with high yields in 5-15min under ambient conditions.

The synthesis of some ß-lactams and investigation of their metal-chelating activity, carbonic anhydrase and acetylcholinesterase inhibition profiles.

ß-Lactam antibiotics are a broad class of antibiotics, consisting of all antibiotic agents that contain a ß-lactam ring in their molecular structures. Synthesis of ß-lactam analogs, which are containing dichloride atoms and N-methyl, N-aromatic rings, was achieved by Schiff bases and dichloroketene compounds. All the synthesized imines and ß-lactam analogs were tested against two physiologically relevant carbonic anhydrase isozymes (hCA I and II) and acetylcholinesterase (AChE). They demponstrated effective inhibitory profiles with Ki values in ranging of 3.22-11.18 nM against hCA I, 3.74-10.41 nM against hCA II, and 0.50-1.57 nM against AChE. On the other hand, acetazolamide and dorzolamide clinically used as CA inhibitors, showed Ki value of 170.34 and 129.26 nM against hCA I, and 115.43 and 135.67 nM against hCA II, respectively. Also, tacrine used as standard AChE inhibitor showed Ki value of 5.70 nM against AChE.

The synthesis of (Z)-4-oxo-4-(arylamino)but-2-enoic acids derivatives and determination of their inhibition properties against human carbonic anhydrase I and II isoenzymes.

The synthesis of (Z)-4-oxo-4-(arylamino)but-2-enoic acid (4) derivatives containing structural characteristics that can be used for the synthesis of several active molecules, is presented. Some of the butenoic acid derivatives (4a, 4c, 4e, 4i, 4j, 4k) are synthesized following literature procedures and at the end of the reaction. In addition, structures of all synthesized derivatives (4a-4m) were determined by (1)H-NMR, (13)C-NMR and IR spectroscopy. Carbonic anhydrase is a metalloenzyme involved in many crucial physiologic processes as it catalyzes a simple but fundamental reaction, the reversible hydration of carbon dioxide to bicarbonate and protons. Significant results were obtained by evaluating the enzyme inhibitory activities of these derivatives against human carbonic anhydrase hCA I and II isoenzymes (hCA I and II). Butenoic acid derivatives (4a-4m) strongly inhibited hCA I and II with Kis in the low nanomolar range of 1.85 ± 0.58 to 5.04 ± 1.46 nM against hCA I and in the range of 2.01 ± 0.52 to 2.94 ± 1.31 nM against hCA II.

Secondary/tertiary benzenesulfonamides with inhibitory action against the cytosolic human carbonic anhydrase isoforms I and II.

Carbonic anhydrase inhibitors of primary sulfonamide type, RSO(2)NH(2), have clinical applications as diuretics, antiglaucoma, antiepileptic, antiobesity and antitumor drugs. Here we investigated inhibition of two human cytosolic isozymes, hCA I and II, with a series of secondary/tertiary sulfonamides, incorporating tosyl moieties (CH(3)C(6)H(4)SO(2)NR1R2). Most compounds inhibited both isoforms in low micromolar range, with inhibition constants between 0.181-6.01 µM against hCA I, and 0.209-0.779 µM against hCA II, respectively. These findings point out that substituted benzenesulfonamides may be used as leads for generating interesting CAIs probably possessing a distinct mechanism of action compared to primary sulfonamides. Indeed, classical RSO(2)NH(2) inhibitors bind in deprotonated form to the Zn(II) ion from the CA active site and participate in many other favorable interactions with amino acid residues lining the cavity. The secondary/tertiary sulfonamides cannot bind to the zinc due to steric hindrance and probably are accommodated at the entrance of the active site, in coumarin binding-site.

Sulfapyridine-like benzenesulfonamide derivatives as inhibitors of carbonic anhydrase isoenzymes I, II and VI.

The inhibition of two human cytosolic carbonic anhydrase (hCA, EC 4.2.1.1) isozymes I, II and human serum isozyme VI, with a series of tosylited aromatic amine derivatives was investigated. The K(I) ranges of compounds 1-14 and acetazolamide against hCA I ranged between 1.130 and- 448.2 µM, against hCA II between 0.103 and- 14.3 µM, and against hCA VI ranged between 0.340 and- 42.39 µM. Tosylited aromatic amine derivatives are thus interesting hCA I, II and VI inhibitors, and might be used as leads for generating enzyme inhibitors eventually targeting other isoforms which have not been assayed yet for their interactions with such agents.

A novel and one-pot synthesis of new 1-tosyl pyrrol-2-one derivatives and analysis of carbonic anhydrase inhibitory potencies.

Here we propose a novel one-pot synthesis of new tosyl-pyrrole derivatives. By means of the new developed method, pyrrole derivatives were synthesized at room temperature in a single step, and a useful method is proposed for the synthesis of similar compounds. Moreover, inhibitions of two human cytosolic carbonic anhydrase (hCA, EC 4.2.1.1) isozymes I and II by 1-tosyl-pyrrole and 1-tosyl-pyrrol-2-on derivatives were investigated. 1-Tosyl-pyrrole, 1-tosyl-1H-pyrrol-2(5H)-one, 5-hydroxy-1-tosyl-1H-pyrrol-2(5H)-one and 5-oxo-1-tosyl-2,5-dihydro-1H-pyrrol-2-yl acetate showed inhibitory action with K(i) values in the range of 14.6-42.4 microM for hCA I and 0.53-37.5 microM for hCA II, respectively. All pyrrole derivatives were competitive inhibitors with 4-nitrophenylacetate as substrate. Some new synthesized pyrrole derivatives showed very effective hCA II inhibitory effects, in the same range as the clinically used sulfonamide acetazolamide, and might be used as leads for generating enzyme inhibitors targeting other CA isoforms.