Burak Barut

Investigation of DNA binding, DNA photocleavage, topoisomerase I inhibition and antioxidant activities of water soluble titanium(IV) phthalocyanine compounds

The binding mode of water soluble peripherally tetra-substituted titanium(IV) phthalocyanine (Pc) compounds Pc1, Pc2 and Pc3 with calf thymus (CT) DNA was investigated by using UV-Vis spectroscopy and thermal denaturation studies in this work. The results of DNA binding constants (Kb) and the changes in the thermal denaturation profile of DNA with the addition of Pc compounds indicated that Pc1, Pc2 and Pc3 are able to bind to CT-DNA with different binding affinities. DNA photocleavage studies of Pc compounds were performed in the absence and presence of oxidizing agents such as hydrogen peroxide (H2O2), ascorbic acid (AA) and 2-mercaptoethanol (ME) using the agarose gel electrophoresis method at irradiation 650 nm. According to the results of electrophoresis studies, Pc1, Pc2 and Pc3 cleaved of supercoiled pBR322 DNA via photocleavage pathway. The Pc1, Pc2 and Pc3 compounds were examined for topoisomerase I inhibition by measuring the relaxation of supercoiled pBR322 DNA. The all of Pc compounds inhibited topoisomerase I at 20 μM concentration. A series of antioxidant assays, including 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, superoxide radical scavenging (SOD) assay and metal chelating effect assay were performed for Pc1, Pc2 and Pc3 compounds. The results of antioxidant assays indicated that Pc1, Pc2 and Pc3 compounds have remarkable superoxide radical scavenging activities, moderate 2,2-diphenyl-1-picrylhydrazyl activities and metal chelating effect activities. All the experimental studies showed that Pc1, Pc2 and Pc3 compounds bind to CT-DNA via minor groove binding, cleave of supercoiled pBR322 DNA via photocleavage pathway, inhibit topoisomerase I and have remarkable superoxide radical scavenging activities. Thanks to these properties the Pc1, Pc2 and Pc3 compounds are suitable agents for photo dynamic therapy.

Electrochemical and spectroelectrochemical properties of thiadiazole substituted metallo-phthalocyanines

4-Thiadiazole substituted phthalonitrile and peripherally tetra-substituted phthalocyanine Cu(II), Fe(II) and Ti(IV)O complexes have been synthesized for the first time. Electrochemical properties of these complexes were determined with voltammetric and in situ spectroelectrochemical measurements. CuPc has redox inactive Cu(2+) center, therefore it gave three Pc based reduction and two Pc based oxidation processes. TiOPc and FePc complexes gave metal based redox processes in addition to Pc based redox reactions due to the redox activity of Ti(4+)O and Fe(2+) metal centers. Although FePc also gave three reduction and two oxidation reactions, peak potentials of these processes are different than those of CuPc due to the different assignments of the redox reactions. TiOPc went to five reduction and one oxidation reactions. Assignments of the redox processes were carried out with in situ spectroelectrochemical measurements. Spectra and color of the electrogenerated redox species of the complexes were also determined with in situ spectroelectrochemical and in situ electrocolorimetric measurements. Distinct color differences between the electrogenerated redox species were observed, which indicated their possible electrochromic usages.

α-Glucosidase inhibitory effect of Potentilla astracanica and some isoflavones: Inhibition kinetics and mechanistic insights through in vitro and in silico studies

α-Glucosidase enzyme inhibitors are clinically used for the treatment of Type 2 diabetes mellitus. We tested α-glucosidase inhibitory effects of Potentilla astracanica Jacq. extracts (1, 2), two compounds isolated from these extracts, prunetin 5-O-β-glucopyranoside (3) and genistein 5-O-β-glucopyranoside (4), and their aglycon forms (5 and 6). All the tested materials possessed remarkable α-glucosidase inhibitor activity compared to the positive control, acarbose. Genistein (6) showed the highest activity with an IC50 value of 1.47 (±0.11) μg/ml. An enzyme kinetics analysis revealed that 3 and 6 were uncompetitive, 5 was noncompetitive, and 4 was competitive inhibitors. Using molecular modeling techniques we tried to provide insight into molecular mechanisms of their activity and how allosteric binding of 6 affected binding interactions between the agonist (maltose) and the enzyme.

Novel water soluble morpholine substituted Zn(II) phthalocyanine: Synthesis, characterization, DNA/BSA binding, DNA photocleavage and topoisomerase I inhibition

In this study, novel peripherally tetra 3-morpholinophenol substituted zinc(II) phthalocyanine (4) and its water soluble form quaternized zinc(II) phthalocyanine (ZnQ) were synthesized for the first time. These novel compounds were characterized by a combination of different spectroscopic techniques such as FT-IR, 1H NMR, 13C NMR, UV-vis and mass. The DNA binding of ZnQ was investigated using UV-vis absorption titration, competitive ethidium bromide, thermal denaturation and viscosity experiments that the ZnQ bound to CT-DNA via intercalation mode. ZnQ indicated photocleavage activity on supercoiled pBR322 plasmid DNA via formation of singlet oxygen under irradiation at 700nm. Besides, the topoisomerase I inhibitory effect experiments showed that ZnQ inhibited topoisomerase I enzyme in a concentration-dependent manner. The bovine serum albumin (BSA) binding experiments indicated that ZnQ bound to proteins through a static quenching mechanism. All of these results claim that ZnQ has potential agent for photodynamic therapy owing to its nucleic acid interactions and photobiological or photochemical properties.

Potential of Potentilla inclinata and its polyphenolic compounds in α-glucosidase inhibition: Kinetics and interaction mechanism merged with docking simulations

In the present study we aimed to identify the α-glucosidase enzyme inhibitory potential of Potentilla inclinata Vill. MeOH and n-BuOH extracts which possessed remarkable α-glucosidase enzyme inhibitory effects with IC50 values of 1.06±0.02 and 0.93±0.01μg/ml respectively, compared to that of acarbose (IC50 31.92±0.17). Thus, BuOH extract was chosen for further phytochemical investigations. A phenolic acid, six flavonol glycosides, and two hydrolysable tannins were isolated from the most active n-BuOH extract of the title plant. Structures of the isolated compounds were elucidated by 1D- and 2D-NMR experiments. All the compounds exhibited remarkable α-glucosidase inhibitory activity compared to the positive control, acarbose. Rutin (2) showed the highest activity with an IC50 value of 26.31±0.02μg/ml. An enzyme kinetics analysis revealed that compounds 5 and 7 were competitive, 4 and 6 noncompetitive, and 3 was uncompetitive inhibitors of α-glucosidase enzyme. Molecular docking studies were performed to get insights into inhibition mechanisms of the isolates considering their inhibition type using various binding sites of the enzyme model we previously reported.

Discovery of potent α-glucosidase inhibitor flavonols: Insights into mechanism of action through inhibition kinetics and docking simulations

Beside other pharmaceutical benefits, flavonoids are known for their potent α-glucosidase inhibition. In the present study, we investigated α-glucosidase inhibitory effects of structurally related 11 flavonols, among which quercetin-3-O-(3″-O-galloyl)-β-galactopyranoside (8) and quercetin 3-O-(6″-O-galloyl)-β-glucopyranoside (9) showed significant inhibition compared to the positive control, acarbose, with IC50 values of 0.97 ± 0.02 and 1.35 ± 0.06 µM, respectively. It was found that while sugar substitution to C3-OH of C ring reduced the α-glucosidase inhibitory effect, galloyl substitution to these sugar units increased it. An enzyme kinetics analysis revealed that 7 was competitive, whereas 1, 2, 8, and 9 were uncompetitive inhibitors. In the light of these findings, we performed molecular docking studies to predict their inhibition mechanisms at atomic level.

Synthesis of Some Novel 2-Substitutedbenzyl-(4)7-phenyl-1H-benzo[d]imidazoles in Mild Conditions as Potent Anti-Tyrosinase and Antioxidant Agents.

Novel 2‐substitutedbenzyl‐4(7)‐phenyl‐1H‐benzo[d]imidazole compounds were synthesized and characterized. Although 2a and 2b were reported previously in the literature, 11 compounds were synthesized (nine of them were newly synthesized) and the tyrosinase inhibitory effects and antioxidant activities of these compounds were studied for the first time. All of the synthesized compounds displayed certain inhibitory effects on tyrosinase, with IC50 values ranging from 37.86 ± 0.24 to 75.81 ± 2.49 μM. Among the compounds, 2j exhibited similar tyrosinase inhibitory effect (IC50 = 37.86 ± 0.24 µM) to the positive control, kojic acid (IC50 = 21.93 ± 0.11 µM). Kinetic studies revealed it to act as non‐competitive tyrosinase inhibitor with a Ki value of 50.2 µM. The antioxidant activities of the compounds were investigated by using in vitro antioxidant assays, including 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP). All of these results indicated that the compounds might have potential application as tyrosinase inhibitors.

Antioxidant capacity, anti-acetylcholinesterase activity and inhibitory effect on lipid peroxidation in mice brain homogenate of Achillea millefolium

Abstract Objective: Achillea millefolium (A. millefolium) is a traditional herbal medicine that contains natural compounds with antioxidant activities and is used for a wide range of conditions among people. The aim of our study was to investigate antioxidant and anti-acetylcholinesterase activities of A. millefolium extracts to determine its potential therapeutic usage in Alzheimer’s disease (AD). Methods: Methanol extracts (ME) and ethanol extracts (EE) of A. millefolium were prepared to determine (a) in vitro antioxidant activities, (b) the effects on acetylcholinesterase kinetics (by using a colorimetric spectroscopic method) and (c) the effects on sodium nitroprusside (SNP)-induced lipid peroxidation in mice brain homogenate. Results: ME had higher antioxidant activities compared to EE. Both extracts displayed a competitive inhibition of acetylcholinesterase; however, the inhibitory activity of ME was higher than EE. The inhibitory constant (Ki) values of ME and EE were found to be 28.43 and 68.47 μg/mL, respectively. Both extracts caused a significant concentration-dependent decrease in malondialdehyde (MDA) contents in mice brain homogenate, indicating a strong inhibition of lipid peroxidation. Conclusions: Our results showed that A. millefolium has a high antioxidant capacity and anti-acetylcholinesterase activity due to its phenolic compounds, suggesting a potential use as adjuvant therapy in neurodegenerative conditions such as AD.

Synthesis of Novel Pyrazolines, Their Boron-Fluorine Complexes, and Investigation of Antibacterial, Antioxidant, and Enzyme Inhibition Activities.

New 3,5‐disubstituted‐2‐pyrazoline derivatives (4–6), their boron‐fluorine complexes (boron (3‐(2′‐aminophenyl),5‐(2′‐/3′‐/4′‐pyridyl)pyrazoline, BOAPPY) (7–9) and boron 1,2′‐diazaflavone complex (BODAF) (11) were synthesized starting from azachalcones (1–3) to diazaflavone (10), respectively. Biological evaluation of compounds 4–9 and 11 showed remarkable antioxidant, antibacterial, and acetylcholinesterase and tyrosinase enzyme inhibition activities. All newly synthesized compounds 4–9 and 11 showed respectable antibacterial effect with minimum inhibitory concentrations in the range of 4.7–150 μg/mL.

Comparison of phenolic profiles and antioxidant activity of three Ornithogalum L. species

Abstract Background Aboveground parts and bulbs of Ornithogalum species are consumed as food and used in traditional medicine in worldwide. Objective It is aimed to report the antioxidant capacity and phenolic compounds content of Ornithogalum sigmoideum, Ornithogalum orthophyllum and Ornithogalum oligophyllum for the first time. Materials and methods Antioxidant activity of the crude methanol extracts of the aerial parts and the bulbs of the species were determined with 1,1-diphenyl-2-picryl-hydrazyl, superoxide radical scavenging, ferrous ion-chelating effect, phosphomolybdenum-reducing antioxidant power and ferric-reducing antioxidant power assay. The ethylacetate, diethylether and water subextracts from leaf and flower were analyzed to quantify selected phenolic compounds by HPLC-UV. Results Among the six extracts, the methanol extract of the aerial parts of O. orthophyllum contained the highest amount of phenolic compounds (GAE, 11.0 mg/g extract). The aerial parts of O. orthophyllum showed higher DPPH and SOD activities than the other extracts with the SC50 values of 0.39±0.05 mg/mL and 0.44±0.08 mg/mL, respectively. Protocatechuic acid, p-hydroxybenzoic acid, vanillic acid and p-coumaric acid were the most abundant compounds at all the subextracts. Conclusion The antioxidant activity is found to be in accordance with the levels of phenolic content in the extracts.