New 1,2,3-triazoles and their oxime derivatives: AChE/BChE enzyme inhibitory and DNA binding properties.

1,2,3-Triazole compounds (1a-3a) and their oxime derivatives (1b-3b) were synthesized. The structures of these synthesized compounds were characterized using common spectroscopic methods. Crystal structures of the compounds 3, 2b and 3b were determined by single crystal X-ray diffraction studies. The acetylcholinesteras (AChE) and butyrylcholinesterase (BChE) cholinesterase inhibitor (ChEI) and DNA/calf serum albumin (BSA) binding properties of the compounds were examined. DNA binding studies have shown that compounds interact with DNA through 1,2,3-triazole and oxime groups. When the binding constant Kb values were compared, it was revealed that compound 3b (Kb = 4.6 × 105 M-1) with oxime in its structure binds more strongly than the others. In addition, in vitro BSA binding studies showed that compounds 1b and 3b exhibited higher binding affinity. These results confirm that the quenching is due to the formation of a compound resulting from the static quenching mechanism, rather than being initiated by a dynamic mechanism. Likewise, when the enzyme activity of the compounds was examined, the compounds exhibited high inhibitory activity against AChE. The highest activity was observed for compounds 2b and 3b (8.6 ± 0.05 and 4.8 ± 0.052 µM). It was observed that the compounds were not selective with respect to BChE. Communicated by Ramaswamy H. Sarma.

Synthesis, DNA Binding Properties, Molecular Docking and ADME Studies of Schiff Base Compound Containing Pyridine-Propargyl Group.

The structure of the pyridine-based Schiff base compound containing the propargyl group was characterized by NMR spectroscopy. Binding of compound 2 with double-stranded fish sperm DNA (Fsds-DNA) was investigated using viscosity measurement studies and UV/VIS and fluorescence spectral techniques. Binding of compound 2 with Fsds-DNA results in minor hypochromism with no change in absorption maxima and fluorescence quenching with almost no shift in emission maxima, which can be attributed to the groove-binding mode of the interaction. The binding constant was found to be 4.7×104  M-1 . The Fsds-DNA viscosity measurement, KI quenching and NaCl quenching studies and the competitive interaction between compound 2 and ethidium bromide with DNA confirm the proposed binding mode. In addition, interactions between compound 2 and the DNA double helix were analysed by molecular docking study in order to determine the binding mode and binding affinity. As a result of molecular docking, the binding affinity of the 2-DNA complex, which has the most stable conformation -8.10 kcal/mol and it is located in its minor groove. In addition, molecular docking and ADME studies for compound 2 were also performed.

Investigation of photoluminescence and DNA binding properties of benzimidazole compounds containing benzophenone group.

The synthesis of benzimidazole compounds containing benzophenone group in accordance with the literature and the investigation of DNA binding properties of these compounds by using UV-vis and photoluminescence spectroscopy methods constitute the basis of this research. The structures of the compounds were determined by methods such as FT-IR, 1H, 13C NMR, UV-vis, Photoluminescence spectroscopy, and X-ray crystallography. By using methods such as UV-vis, Photoluminescence spectroscopy, and viscosity tests, information were collected about the binding types, binding mode, and binding energies of the compounds with DNA. In addition, the binding interactions of the compounds with DNA were investigated using the molecular docking technique. Using this information, calibration equations, correlation coefficients (r2), and DNA binding constants (Kb) were calculated for their compounds. The binding constants (Kb) calculated for substances A, B, and C were found to be 3.0 × 104, 7.0 × 104, and 3.0 × 104 M-1, respectively. UV-vis, EB competitive binding, and viscosity tests showed that the compounds tended to bind to the DNA structure via the groove binding mode. At the end of molecular docking studies, it was determined that compound B showed the best DNA binding activity in in vitro studies. Compared with the studies in the literature, it is thought that the synthesized compounds can take place in cancer drug research as DNA binding agents.Communicated by Ramaswamy H. Sarma.

Synthesis, in silico and in vitro studies of hydrazide-hydrazone imine derivatives as potential cholinesterase inhibitors.

A series of hydrazide-hydrazone imine derivative compounds (3a-k) were synthesized and their structures characterized using FTIR, 1 H, and 13 C (NMR) spectroscopic methods. In addition, molecular structures of compounds 3a, 3d, and 3g were elucidated by X-ray diffraction technique. In vitro inhibition activities of hydrazide-hydrazone imine derivatives against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were investigated. Compound 3i (IC50 = 2.01 µM) exhibited the best inhibitory activity against AChE, comparable to the control Galantamine (IC50 = 2.60 µM). Against BChE, compound 3h (IC50 = 2.83 µM) showed the best inhibitory property which is higher control Galantamine (IC50 = 3.70 µM). The Ki values of compound 3i (Ki = 0.63 µM) and compound 3h (Ki = 0.94 µM) that have the strongest inhibitory potential were determined against AChE and BChE, respectively. According to the docking result, the most stable conformation of AChE and compound 3i showed that it has a binding affinity of -10.82 kcal/moL. The binding affinity of the most stable conformation formed by BChE and compound 3h is -8.60 kcal/moL. Finally, in silico results and pharmacokinetic parameters of ADME showed that these compounds have good oral bioavailability properties.

Synthesis, characterization and docking studies of benzenesulfonamide derivatives containing 1,2,3-triazole as potential inhibitor of carbonic anhydrase I-II enzymes.

Carbonic Anhydrases (CAs) are an important family of metalloenzymes that contain zinc (Zn2+) ions in their active site and catalyze the conversion of carbon dioxide to bicarbonate and proton and found in all living organisms. Sulfonamides are well-known inhibitors of CAs isoenzymes. In this study, a series of benzenesulfonamide derivatives (9a-h) containing 1,2,3-triazole-moiety were designed, synthesized and their structures were characterized by spectroscopic methods. In addition, molecular structures of compounds 5a, 5 b, 9e and 9f were elucidated by X-ray diffraction technique. To investigate drug similarity of 9a-h compounds, Lipinski's five rules (ADMET: absorption, distribution, metabolism, excretion and toxicity) were carried out by in silico studies. According to results, the compounds showed drug-like properties. Docking studies were applied to determine the scores, interactions and binding modes of compounds 9a-h against hCA I and hCA II enzymes. Compound 9c (-5.13 kcal/mol docking score) against hCA I enzyme and 9 h (-5.32 kcal/mol docking score) against hCA II enzyme showed potent inhibitory properties. The binding interactions of the compounds with the carbonic anhydrases were examined by docking studies.Communicated by Ramaswamy H. Sarma.

Synthesis, Biological Evaluation and Docking Study of Mono- and Di-Sulfonamide Derivatives as Antioxidant Agents and Acetylcholinesterase Inhibitors.

Mono(M1-M5)- and di(DM1-DM5)-sulfonamide derivatives were synthesized by the reaction of 4-iodobenzenesulfonyl chloride compound and aniline derivatives in basic medium. The structures of sulfonamide derivatives were characterized by spectroscopic and X-ray diffraction methods. All compounds were screened for acetylcholinesterase (AChE) inhibitory studies and 2,2-diphenyl-1-picrylhydrazil (DPPH) radical scavenging activities. Among the compounds tested, compound M1 showed the best activity against both AChE (IC50 =42.09 µg/mL for AChE) and DPPH (IC50 =9.94 µg/mL for DPPH). By placing compounds at the active site of AChE, their binding energies and modes were determined. Docking studies were performed in order to investigate binding interaction between the synthesized compounds and AChE. The most active M1 compound showed its low CDOCKER energy (-65,834 kcal/mol).

Enzyme Inhibition Properties and Molecular Docking Studies of 4-Sulfonate Containing Aryl α-Hydroxyphosphonates Based Hybrid Molecules.

In this study, a series of new hybrid molecules containing two important functional groups on the same skeleton were designed. 4-Hydroxybenzaldehyde and its two different derivatives were converted into their respective sulphonates by interacting with tosylchloride and methanesulfonyl chloride. Then, the desired molecules were synthesized by adding diethoxyphosphonate to the aldehyde group. Also, novel synthesis of hybrid compounds (4a-c and 5a-c) were tested toward some metabolic enzymes like carbonic anhydrase I and II isoenzymes (hCA I and hCA II) and acetylcholinesterase (AChE) enzyme. The synthesis of hybrid compounds (4a-c and 5a-c) showed Ki values of in range of 25.084±4.73-69.853±15.19 nM against hCA I, 32.325±1.67-82.761±22.73 nM against hCA II and 1.699±0.25 and 3.500±0.91 nM against AChE. For these compounds, compound 4c showed maximum inhibition effect against hCA I and hCA II isoenzymes and compound 5b showed maximum inhibition effect against AChE enzyme. By performing docking studies of the most active compounds for their binding modes and interactions were determined.

N-substituted benzenesulfonamide compounds: DNA binding properties and molecular docking studies.

Benzenesulfonamide-based imine compounds 5-8 were prepared and screened for their binding properties to the FSdsDNA. The structures of synthesized compounds were elucidated by the spectroscopic and analytical methods. Compounds 5-8 were screened for their interactions with the FSdsDNA. Compound 8 showed the highest binding affinity to the FSdsDNA with intrinsic binding constant of 3.10 × 104 M-1. The compounds caused the quenching of the DNA-EB emission indicating displacement of EB (ethidium bromide) from the FSdsDNA. Finally, the binding interactions between the DNA and binder molecules 5-8 were examined by the molecular docking studies. The compounds locate approximately same region of the minor groove of DNA via hydrogen bonding contacts between the sulfonamide oxygen atoms and the DG10/DG16 nucleotides of DNA.Communicated by Ramaswamy H. Sarma.

A novel Schiff base: Synthesis, structural characterisation and comparative sensor studies for metal ion detections.

A novel Schiff base ligand was synthesized by the condensation reaction of 2,6-diformylpyridine and 4-aminoantipyrine in MeOH and characterised by its melting point, elemental analysis, FT-IR, (1)H, (13)C NMR and mass spectroscopic studies. Molecular structure of the ligand was determined by single crystal X-ray diffraction technique. The electrochemical properties of the Schiff base ligand were studied in different solvents at various scan rates. Sensor ability of the Schiff base ligand was investigated by colorimetric and fluorometric methods. Visual colour change of the ligand was investigated in MeOH solvent in presence of various metal ions Na(+), Mg(2+), Al(3+), K(+), Cr(3+), Mn(2+), Fe(3+), Co(2+), Ni(2+), Cu(2+), Zn(2+), Cd(2+), Hg(2+) and Pb(2+). Upon addition of Al(3+) ion into a MeOH solution of the ligand, an orange colour developed which is detectable by naked eye. Fluorescence emission studies showed that the ligand showed single emission band at 630-665nm upon excitation at 560nm. Addition of metal ions Na(+), Mg(2+), K(+), Cr(3+), Mn(2+), Fe(3+), Co(2+), Ni(2+), Cu(2+), Zn(2+), Cd(2+), Hg(2+) and Pb(2+) (1:1M ratio) cause fluorescence quenching, however addition of Al(+3) resulted in an increase in fluorescence intensity. No significant variation was observed in the fluorescence intensity caused by Al(3+) in presence of other metal ions. Therefore, the Schiff base ligand can be used for selective detection of Al(3+) ions in the presence of the other metal ions studied.