Yakup Budak

Synthesis, characterization, anticancer, antimicrobial and carbonic anhydrase inhibition profiles of novel (3aR,4S,7R,7aS)-2-(4-((E)-3-(3-aryl)acryloyl) phenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione derivatives

In the present study, a series of new hybrid compounds containing chalcone and methanoisoindole units 7a-n ((3aR,4S,7R,7aS)-2-(4-((E)-3-(3-aryl)acryloyl) phenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione) were synthesized, characterized and investigated for their anticancer activity against C6 gliocarcinoma cell in rats, and antimicrobial activity against some human pathogen microorganisms. The compounds 7e, 7h, 7j, 7k, 7L and 7n showed very high anticancer activity with the inhibition range of 80.51-97.02% compared to 5-FU. Some of the compounds exhibited anti-microbial activity. Also, they evaluated for inhibition effects against human carbonic anhydrase I, and II isoenzymes (hCA I and II) with Ki values in the range of 405.26-635.68pM for hCA I, and 245.40-489.60pM for hCA II, respectively. These results demonstrated that 3aR,4S,7R,7aS)-2-(4-((E)-3-(3-aryl)acryloyl)phenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione derivatives could be used in different biomedical applications.

Synthesis of chalcone-imide derivatives and investigation of their anticancer and antimicrobial activities, carbonic anhydrase and acetylcholinesterase enzymes inhibition profiles

Abstract The new 1-(4-(3-(aryl)acryloyl)phenyl)-1H-pyrrole-2,5-diones (5a–g) were prepared from 4′-aminchalcones (3a–g) and screened for biological activities. All compounds (3a–g and 5a–g), except 3d and 3e displayed good cytotoxic activities with IC50 values in the range of 7.06–67.46 μM. IC50 value of 5-fluorouracil (5-FU) was 90.36 μM. Moreover, most of compounds 5a–g showed high antibacterial activity with 8–20 mm of inhibition zone (19–25 mm of Sulbactam-Cefoperazone (SCF)). In addition, they showed good inhibitory action against acetylcholinesterase (AChE), and human carbonic anhydrase I, and II (hCA I and hCA II) isoforms. Also, these compounds demonstrated effective inhibition profiles with Ki values of 426.47–699.58 nM against hCA I, 214.92–532.21 nM against hCA II, and 70.470–229.42 nM against AChE. On the other hand, acetazolamide, clinically used drug, showed a Ki value of 977.77 ± 227.4 nM against CA I, and 904.47 ± 106.3 nM against CA II, respectively. Also, tacrine inhibited AChE showed a Ki value of 446.56 ± 58.33 nM.

Synthesis and Carbonic Anhydrase Inhibition of Tetrabromo Chalcone Derivatives

In the present study, human carbonic anhydrase (hCA) enzyme was purified and characterized from fresh blood human red cells by Sepharose‐4B‐l‐tyrosine‐sulfanilamide affinity gel chromatography. Secondly, a series of new tetrabromo chalcone derivatives containing 4,7‐methanoisoindol‐1,3‐dione (2a–i) were synthesized from the addition of Br2 to related chalcone derivatives (1a–i). The structures of the new molecules (2a–i) were confirmed by means of 1H NMR, 13C NMR and elemental analysis. Finally, the inhibitory effects of 2a–i on CA activities were investigated using the esterase method under in vitro conditions. The compounds 2a–i exhibited excellent inhibitory effects, in the low nanomolar range, with Ki values in the range of 11.30–21.22 nM against hCA I and in the range of 8.21–12.86 nM against hCA II. Our findings suggest that the new compounds 2a–i have superior inhibitory effect over acetazolamide (AZA), which is used as clinical CA inhibitor, with obtained Ki values of 34.50 and 28.93 nM against the hCA I and II isozymes, respectively. In addition to the inhibition assays, molecular modeling approaches were implemented for prediction of the binding affinities of compounds 2a and 2c, which had the highest inhibition effects, against the hCA I and II isozymes.

Synthesis and investigation of antibacterial activities and carbonic anhydrase and acetyl cholinesterase inhibition profiles of novel 4,5-dihydropyrazol and pyrazolyl-thiazole derivatives containing methanoisoindol-1,3-dion unit

ABSTRACT Novel 4,5-dihydropyrazole derivatives (3a–i), 3-(4-((3aR,4S,7R,7aS)-1,3-dioxo-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindol-2(3H)-yl)phenyl)-5-phenyl-4,5-dihydro-1H-pyrazole-1-carbothio amide, were obtained by the addition of thiosemicarbazide (2) to the chalcones (1a–i). The addition–cyclization of 2,4′-dibromoacetophenone (4) to pyrazole derivatives (3a–i) gave the new pyrazolyl-thiazole derivatives (5a–i), (3aR,4S,7R,7aS)-2-(4-(1-(4-(4-bromophenyl)thiazol-2-yl)-5-phenyl-4,5-dihydro-1H-pyrazol-3-yl)phenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione. Antibacterial and acetylcholinesterase (AChE) enzyme and human carbonic anhydrase (hCA) I, and II isoform inhibitory activities of the compounds 3a–i and 5a–i were investigated. Some of the compounds showed promising antibacterial activity. In addition, the hCA II and I were effectively inhibited by the lately synthesized derivatives, with Ki values in the range of 18.90 ± 2.37 −58.25 ± 13.62 nM for hCA II and 5.72 ± 0.98 −37.67 ± 5.54 nM for hCA I. Also, the Ki parameters of these compounds for AChE were obtained in the range of 25.47 ± 11.11 − 255.74 ± 82.20 nM. Also, acetazolamide, clinical molecule, was used as a CA standard inhibitor that showed Ki value of 70.55 ± 12.30 nM against hCA II, and 67.17 ± 9.1 nM against hCA I, and tacrine inhibited AChE showed Ki value of 263.67 ± 91.95. GRAPHICAL ABSTRACT

Potassium–Tertiary Butoxide–Assisted Addition of Thioglicolic Acid to Chalcone Derivatives Under Solvent-Free Conditions

A series of chalcone derivatives containing thioglicolic acid (4a–j) was prepared by addition of thioglicolic acid to the chalcones (3a–j) in the presence of KOt-Bu under solvent-free conditions. The mechanistic pathway of the reaction can be explained by the Michael-type addition of thioglicolic acid to chalcone derivatives (3a–j).

Iodine-Catalyzed Addition of Methyl Thioglycolate to Chalcones

Abstract A series of novel β-mercapto carbonyl compounds (3a–z), methyl 2-(3-oxo-1,3-diarylpropylthio)acetate, were synthesized and characterized via iodine-catalyzed addition of methyl thioglycolate to chalcones (1a–z). Supplemental materials are available for this article. Go to the publishers online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file. GRAPHICAL ABSTRACT

Cyclohexenones Through Regioselective Addition of 1,3-Dicarbonyl Compounds to Terpenoid-Like Bischalcones

Abstract Terpenoid-like bischalcones (3 and 4) were synthesized from the reaction of α- and β-ionones and benzaldehydes in excellent yields. The Michael addition of 1,3-dicarbonyl compounds to bischalcones (3 and 4) resulted in the formation of cyclohexenones derivatives (10a–d and 14a, b) via regioselective addition of 1,3-dicarbonyls and then cyclization.

Purification of glutathione S-transferase enzyme from quail liver tissue and inhibition effects of (3aR,4S,7R,7aS)-2-(4-((E)-3-(aryl)acryloyl)phenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione derivatives on the enzyme activity

The use of quail meat and eggs has made this animal important in recent years, with its low cost and high yields. Glutathione S‐transferases (GST, E.C.2.5.1.18) are an important enzyme family, which play a critical role in detoxification system. In our study, GST was purified from quail liver tissue with 47.88‐fold purification and 12.33% recovery by glutathione agarose affinity chromatography. The purity of enzyme was checked by SDS‐PAGE method and showed a single band. In addition, inhibition effects of (3aR,4S,7R,7aS)‐2‐(4‐((E)‐3‐(aryl)acryloyl)phenyl)‐3a,4,7,7a‐tetrahydro‐1H‐4,7methanoisoindole‐1,3(2H)‐dion derivatives (1a–g) were investigated on the enzyme activity. The inhibition parameters (IC50 and Ki values) were calculated for these compounds. IC50 values of these derivatives (1a–e) were found as 23.00, 15.75, 115.50, 10.00, and 28.75 μM, respectively. Ki values of these derivatives (1a–e) were calculated in the range of 3.04 ± 0.50 to 131.50 ± 32.50 μM. However, for f and g compounds, the inhibition effects on the enzyme were not found.

Synthesis of 1-phenyl -1, 2-cyclohexadiene and 1-(2-bromocyclohex-2-en-1-yl)benzene and Wurtz-like condensation products in the reaction of 1-(2,3-dibromocyclohex-1-en-1-yl) benzene with zinc

The base-catalysed elimination of 1-(2-bromocyclohex-2-en-1-yl)benzene 1 and the zinc-catalysed elimination of 1-(2,3-dibromocyclohex-1-en-1-yl)benzene 9 have been used for the synthesis of 1-phenyl-1,2-cyclohexadiene 2; reaction of 9 with zinc in THF resulted in the formation of two isomeric Wurtz-like condensation products 3 and 4, but the reaction of 1 with t-BuOK gave the allene 2.

Synthesis, characterization, and investigations of antimicrobial activity of 6,6-dimethyl-3-aryl-3′,4′,6,7-tetrahydro-1′H,3H-spiro[benzofuran-2,2′-naphthalene]-1′,4(5H)-dione

ABSTRACT Chalcone-like compounds 3a–l, 2-(benzylidene)-3,4-dihydronaphthalen-1(2H)-one, were synthesized from the addition of different benzaldehyde derivatives (2a–l) to 1,2,3,4-tetrahydro-1-napthalone (1) in basic medium. Mn(OAc)3-mediated addition of dimedone (4) to chalcone-like compounds gave the spirobenzofuran derivatives (5a-l), 6,6-dimethyl-3-aryl-3′,4′,6,7-tetrahydro-1′H,3H-spiro[benzofuran-2,2′-naphthalene]-1′,4 (5H)-dione, in good yields. The structures of synthesized compounds 5a–l were elucidated on basis of spectral data (NMR, IR) and elemental analysis. In addition, their antibacterial activities were screened against some human pathogenic microorganisms. GRAPHICAL ABSTRACT