Meliha Burcu Gürdere

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.

The synthesis and screening of the antimicrobial activity of some novel 3-(furan-2-yl)-1-(aryl)-3-(phenylthio) propan-1-one derivatives

A series of thiophenol adducts (3a–m) were prepared by addition of thiophenol to chalcones (1a–m) in the presence of a catalytic amount of KOt-Bu in solvent free conditions. In addition, the antibacterial and antifungal in vitro properties were tested against some human pathogenic microorganisms by employing the disk diffusion technique. A majority of compounds were remarkably active against several of the microorganisms. Compound 3i was determined to be the most active compound.

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).

Aluminum chloride–catalyzed C-alkylation of pyrrole and indole with chalcone and bis-chalcone derivatives

ABSTRACT The AlCl3-catalyzed alkylation of pyrrole (2) with chalcone (1a–i) at a ratio of 8:1 in the presence of 10 mol% AlCl3 gave the solely 2-alkyl pyrroles (3a–i) at room temperature for 12 in good yields. The same reaction was performed with pyrrole (2) and chalcone at a ratio of 1:3 in CH3CN at rt for 3 h to achieve 2,5-dialkyl pyrroles (4a–f). In addition, the reaction of the pyrrole (2) and indole (7) on 1,4-phenylene bis-chalcones (5a–g) at the ratio of 8:1 at rt for 24 h gave the double-addition products 6a–g and 8a–g in good yields, respectively. The structure of the products was confirmed by 1H and 13C NMR spectroscopy and elemental analysis. GRAPHICAL ABSTRACT

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, 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

Triethylamin-mediated addition of 2-aminoethanethiol hydrochloride to chalcones: Synthesis of 3-(2-aminoethylthio)-1-(aryl)-3-(thiophen-2-yl) propan-1-ones and 5,7-diaryl-2,3,6, 7-tetrahydro-1,4-thiazepines

ABSTRACT The triethylamin-mediated addition of 2-aminoethanethiol hydrochloride to chalcone analogs was investigated. This addition, bearing a 2-thienyl group at the 3-position, gave the only addition adduct at room temperature in 3 h, whereas the chalcones bearing the 2-furyl group at the 1-position gave an addition-cyclization product (1, 4-thiazepine) in the same conditions. The effect of the groups to the reaction was investigated by changing the 1- and 3-position groups. The chalcones bearing the 2-thienyl group at the 1-position and the others afforded the mixture of products in different ratio at rt for 0.5–24 h. Moreover, the addition–cyclization products (1,4-thiazepine) were obtained under reflux conditions in 36 h. The structures of the synthesized compounds were elucidated by 1H NMR, 13C NMR, infrared, and elemental analysis. GRAPHICAL ABSTRACT

Synthesis and Characterization of Some Novel Multisubstituted 6,7-Dihydro-5H-cyclopenta[b]pyridine Derivatives

Abstract In this study, we describe systematic preparation of a series of aryl-substituted pyridine derivatives. The 1,5-dicarbonyls (3a–i) were prepared in the solvent-free conditions starting from chalcone derivatives (1a–i). The target compounds, 4-aryl-2-(thiophen-3-yl)-6,7-dihydro-5H-cyclopenta[b]-pyridine derivatives (5a–i), were synthesized by a cyclization reaction of the 1,5-dicarbonyls (3a–i) with ammonium acetate (NH4OAc) in acetic acid. The characterization of synthesized compounds was proved by elemental analyses, infrared, mass spectrometry, and 1H and 13C NMR spectroscopy. [Supplementary materials are available for this article. Go to the publishers online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.] GRAPHICAL ABSTRACT