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Various Vinca species have been traditionally used for their antihypertensive, sedative, and hemostatic properties, as well as for treating diabetes. In this study, some flavonoids, phenolic acids and iridoids were isolated from an endemic Vinca species, Vinca soneri for the first time. α-Glucosidase inhibitory effects of the isolates were tested and kaempferol-3-O-α-rhamnopyranosyl (1→6) β-galactopyranoside (1) was found to be the most active one with an IC 50 value of 285.73 ±7.35 μM. Enzyme kinetic assay revealed that it inhibited α-glucosidase in competitive manner. Molecular geometry of 1 was predicted and Frontier molecular orbital analysis was performed using Density Functional Theory (DFT) calculations. Molecular docking and MM-GBSA calculations predicted good fit for 1 in the enzyme active site and key interactions with the catalytic residues. As a result, current study identifies 1 as a promising competitive α-glucosidase inhibitor to be developed as a potential antidiabetic drug candidate., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

This study aimed to evaluate and compare the antioxidant capacity and enzyme inhibitory activity of extracts, sub-extracts, and fractions prepared from the aerial parts and roots of A. pseudocartalinica. The phytochemical content of the active extracts was also analyzed. According to the results, ellagic acid (38.42 mg/g) was the major compound in the aerial part methanol extract and catechin (185.30 mg/g) in the root methanol extract. The DPPH inhibition activity of all fractions was monitored, with the most active one (Fr B) reaching an IC 50 value of (4.92±0.59 μg/mL). All the fractions prepared from the aerial parts' water sub-extract showed higher a-glucosidase inhibitory activity than the positive control acarbose. In the tyrosinase assay, Fr B (58.81±7.50 μg/mL) exhibited the highest inhibitory actions among all fractions. The structure of the major substances of the most active fraction were elucidated as quercetin 7-O-β-glucopyranosyl-3-O-β-glucuronopyranoside- (1), and α-[(2-formyl-5-hydroxymethyl)pyrrol-1-yl]aspartic acid (2)., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Type 2 diabetes (T2DM) is a progressive metabolic disease associated with high blood sugar levels that affects 537 million people worldwide. This study aim is to investigate the potential for use in the treatment of T2DM by examining the in vitro glucosidase inhibitory effects of novel synthesized metallophthalocyanines. For this reason, we have synthesized cobalt(II), copper(II) phthalocyanines (3PY-ON-CoQ, 3PY-ON-CuQ) that are both water-soluble and do not aggregate in water. These compounds were characterized by using various spectroscopic methods. The α-glucosidase inhibitory properties of 3PY-ON-CoQ and 3PY-ON-CuQ were carried out using the spectrophotometric method. Then, Lineweaver-Burk and Dixon plots were examined to determine the inhibitory type and constant (K i ). The IC 50 values of 3PY-ON-CoQ and 3PY-ON-CuQ were 6.85 ± 1.25 μM and 55.09 ± 2.64 μM, respectively. Both compounds displayed mixed inhibitory effects on α-glucosidase according to Lineweaver-Burk plots. The K i values of 3PY-ON-CoQ and 3PY-ON-CuQ were calculated as 6.30 ± 1.55 μM and 54.25 ± 1.20 μM, respectively. The results of this work may lead to the discovery of new compounds for the treatment of T2DM., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier Inc.)

This study aimed to evaluate the potential of Hedera colchica as an alternative to Hedera helix species for the treatment of mild inflammatory conditions of the upper respiratory tract and chronic inflammatory bronchial diseases. The H. colchica extract with the highest saponin content ( C3S ; 468.19 ± 16.01 mg HE/g dry weight) and the extract with the highest total phenol content ( C1F ; 108.60 ± 5.61 mg GAE/g dry weight). Chemical analysis and standardisation of the extract with the highest selective COX-2 inhibitory effect was performed using the LC-MS/MS technique. It was determined that the substances found in the highest ratio in the C1F extract were quinic acid (45.909 µg/g extract) and hesperidin (37.077 µg/g extract). As a result, secondary metabolites, in addition to saponins, found in Hedera species may also contribute to the extract's effectiveness, more potent extracts can be obtained compared to the total extract-containing preparations available in the market.

α-Glycosidase inhibition is one of the main approaches to treat Diabetes mellitus. Polyphenolic moieties are known to be responsible for yielding exhibit potent α-glycosidase inhibitory effects. In addition, compounds containing benzothiazole and Schiff base functionalities were previously reported to show α-glycosidase inhibition. In this paper, the synthesis of seven new phloroglucinol-containing benzothiazole Schiff base derivatives through the reaction of 6-substituted-2-aminobenzothiazole compounds with 2,4,6-trihydroxybenzaldehyde using acetic acid as a catalyst was reported. The synthesized compounds were characterized using spectroscopic methods such as FT-IR, 1 H NMR, 13 C NMR, and elemental analysis. The synthesized compounds were evaluated for their inhibitory effects on α-glycosidase, compounds 3f and 3g were found to show significant inhibitory properties when compared to the positive control. The IC 50 values of 3f and 3g were calculated as 24.05 ± 2.28 and 18.51 ± 1.19 µM, respectively. Kinetic studies revealed that compounds 3f and 3g exhibited uncompetitive mode of inhibition against α-glycosidase. Molecular modeling predicted druglikeness for the title compounds and underpinned the importance of phloroglucinol hydroxyls for interacting with the key residues of α-glycosidase., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Alzheimer's disease (AD), one of the main causes of dementia, is a neurodegenerative disorder. Cholinesterase inhibitors are used in the treatment of AD, but prolonged use of these drugs can lead to serious side effects. Drug repurposing is an approach that aims to reveal the effectiveness of drugs in different diseases beyond their clinical uses. In this work, we investigated in vitro and in silico inhibitory effects of 11 different drugs on cholinesterases. The results showed that trimebutine, theophylline, and levamisole had the highest acetylcholinesterase inhibitory actions among the tested drugs, and these drugs inhibited by 68.70 ± 0.46, 53.25 ± 3.40, and 44.03 ± 1.20%, respectively at 1000 µM. In addition, these drugs are bound to acetylcholinesterase via competitive manner. Molecular modeling predicted good fitness in acetylcholinesterase active site for these drugs and possible central nervous system action for trimebutine. All of these results demonstrated that trimebutine was determined to be the drug with the highest potential for use in AD., (© 2024 The Authors. Drug Development Research published by Wiley Periodicals LLC.)

In this work, the phytochemical characterization, biological activity, and cytotoxic mechanism of aerial and rhizome methanol extracts (SME and RME) of Epimedium pubigerum were investigated to demonstrate its potential usage in the treatment of lung cancer. LC-HRMS analysis, total phenolic/flavonoid content assay, DPPH radical scavenging assay, DNA interaction, cytotoxicity, and western blotting were investigated using different methods. Fumaric acid was found to be the most abundant compound in both extracts. SME and RME were cytotoxic on A549 cells concentration-dependently. Also, in vitro scratch assay showed that SME and RME led to a significant anti-migratory effect at 1 mg/mL. Cytochrome c, p53, and caspase 3 expression significantly increased in the presence of RME compared to the control. All of these results claimed that RME might be suggested as a theoretically more effective phytotherapeutic agent for lung cancer compared to the effect seen with the SME., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Azoles, which have been used for antifungal chemotherapy for decades, have recently been of interest for their efficacy against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). There is little known about the potential of azoles against BChE, however there is none regarding their inhibitory effects against mutants of BChE. In the current study, an azole library of 1-aryl-2-(1H-imidazol-1-yl)ethanol/ethanone oxime esters were tested against AChE and BChE, which yielded derivates more potent than the positive control, galantamine, against both isoforms. Kinetic analyses were performed for wildtype and mutant (A328F and A328Y) inhibition for the two most potent BChE inhibitors, pivalic and 3-bezoylpropanoic acid esters of 2-(1H-imidazol-1-yl)-1-(2-naphthyl)ethanol, which were found to have great affinity to the wildtype and mutant BChE types with K i values as low as 0.173 ± 0.012 µM. The compounds were identified to show linear competitive or mixed type inhibition. Molecular modeling confirmed these kinetic data and provided further insights regarding molecular basis of BChE inhibition by the active derivatives. Thus, current study suggests new azole derivatives with promising cholinesterase inhibitory effects and reveals the first set of information to promote our understanding for the inhibitory behavior of this class against the mutant BChE forms., (© 2023 The Authors. Drug Development Research published by Wiley Periodicals LLC.)

Tyrosinase is a key enzyme in the biosynthesis of melanin, which is responsible for the browning of foods as well as many skin disorders. In order to develop new anti-browning agents with dual antioxidant and anti-tyrosinase capacities, a series of 30 thiazolyl hydrazone derivatives were synthesized. Among the molecules prepared, 6 and 30 were found to be the most potent tyrosinase inhibitors with IC 50 values ​​comparable to that of kojic acid. Interestingly, 6 also has the highest radical scavenging activity among the prepared molecules. The inhibition kinetics study indicated that 6 is a non-competitive inhibitor while 30 inhibits tyrosinase competitively. The anti-browning assay of fresh-cut potato slices revealed that 6 and 30 are potent anti-browning agents with a capacity as high as kojic acid. The mechanisms of free radical scavenging and tyrosinase inhibition have been fully investigated in silico using computational kinetics, molecular docking, and molecular dynamics simulations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Turkey is the world's leading producer of figs, a typical Mediterranean fruit. The fig, Ficus carica L. (Moraceae), has been widely cultivated since ancient times due to the nutritional value of its fruits. It was aimed to investigate the phytochemical characterization and biological properties of F. carica leaf extracts in order to determine their potential for use in the treatment of various diseases. F. carica leaves were extracted in 70% methanol at 40 °C under reflux. To obtain extracts of different polarities, the crude extract was fractionated with n -hexane, dichloromethane, and n -butanol. Phenolic content was determined using liquid chromatography-high resolution mass spectrometry (LC-HRMS). 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and antityrosinase activities of all extracts were investigated using spectrophotometric methods. Furthermore, the DNA-damage protective properties of extracts were investigated using electrophoretic methods. The n -butanol extract was found to have the highest total phenolic content, with 72.58 ± 4.52 mg GAE/g dry weight. According to LC-HRMS analysis, rutin (40.13 g/kg) was the most abundant compound in the n -butanol extract. The n -butanol extract, which was found to have the highest tyrosinase inhibitory effects among the extracts, demonstrated radical scavenging activity of 37.01 ± 1.15% and 82.57 ± 0.88% at 80 and 200 μg/mL, respectively. The n -butanol extract had the highest protective effects against Fenton's reagent, UV radiation, and singlet oxygen. Given these findings, it is possible to argue that F. carica leaves can be evaluated for developing products that could be used to treat various diseases., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© TÜBİTAK.)

In this study, some novel mono- and di- O -β-D-glycopyranosyl chalcone analogs were designed, synthesized, and characterized. The chalcone derivatives were synthesized with good yields by base-catalyzed Claisen-Schmidt condensation in EtOH solution. Then these chalcones were reacted with TAGBr (2,3,4,6-tetra-O-acetyl-α-D-glucopyranosylbromide) in dry acetone under the anhydrous condition at 0-5 °C. Deacylated was carried out by the Zemplen's method with NaOCH 3 in dry methanol results in substituted chalcone- O -glycosides (mono- and di- O -β-D-glycopyranosyl chalcone analogs). The chemical structures of all synthesized compounds were elucidated based on IR, NMR spectral data, and mass spectrometry. Further, the compounds ( 7a-c, 8a-c, 12a-c, 16a-c, and 17a-c ) were tested for their enzyme inhibition activity against α-glycosidase, tyrosinase, and AChE with in vitro and in silico analysis. Amongst them, compounds 12a-c, 16a-c, and 17a-c displayed moderate or less enzyme inhibition activity against α-glycosidase while other compounds 7a-c and 8a-c ) were not active. Remarkably interesting enzyme inhibition effects, with IC 50 values below 30.59 ± 0.30 μM were recorded with 7c (IC 50 =11.07 ± 0.55 μM) against tyrosinase., Competing Interests: Conflict of interest The authors declare no conflict of interest or personal relationship for the contents and writing of the paper., (© TÜBİTAK.)

Polydatin or piceid, is the 3-O-glucoside of resveratrol and is found abundantly in grapes, peanuts, wine, beer, and cacao products. Although anticancer activity of polydatin was reported before, and potential antiproliferative mechanisms of polydatin have been proposed, its direct effects on DNA and inhibitory potential against topoisomerase enzymes have remained unknown. In this study we aimed to reveal the link between polydatin's effects on DNA and DNA-topoisomerases and its antiproliferative promise. For this purpose, we evaluated the effects of polydatin on DNA and DNA topoisomerase using in vitro and in silico techniques. Polydatin was found to protect DNA against Fenton reaction-induced damage while not showing any hydrolytic nuclease effect. Further, polydatin inhibited topoisomerase II but not topoisomerase I. According to molecular docking studies, polydatin preferably showed minor groove binding to DNA where the stilbene moiety was important for binding to the DNA-topoisomerase II complex. As a result, topoisomerase II inhibition might be another anticancer mechanism of polydatin., (© 2022 Wiley-VHCA AG, Zurich, Switzerland.)

Cholinesterase inhibition is of great importance in the fight against neurodegenerative disorders such as Alzheimer's disease. Azole antifungals have come under the spotlight with recent discoveries that underline the efficacy and potential of miconazole and its derivatives against cholinesterase enzymes. In this study, we evaluated a library of azoles against acetylcholinesterase and butyrylcholinesterase using in vitro and in silico methods to identify potent inhibitors. Low micromolar IC 50 values were obtained for imidazole derivatives, which were further tested and found potent competitive cholinesterase inhibitors via enzyme kinetics study. The active derivatives showed negligible toxicity in in vitro cytotoxicity tests. Molecular modeling studies predicted that these derivatives were druglike, could penetrate blood-brain barrier, and tightly bind to cholinesterase active site making key interactions via the imidazole moiety at protonated state. Thus, current study identifies potent and competitive cholinesterase inhibitor azoles with minor toxicity and potential to pass into the central nervous system., (© 2022 Wiley-VHCA AG, Zurich, Switzerland.)

Nafimidone is known for its clinical antiepileptic effects and alcohol derivatives of nafimidone were reported be potent anticonvulsants. These compounds are structurally similar to miconazole, which is known to inhibit cholinesterases, protect neurons, and ameliorate cognitive decline. Herein, we aimed to reveal the potential of three nafimidone alcohol esters (5 g, 5i, and 5 k), which were previously reported for their anticonvulsant effects, against co-morbidities of epilepsy such as inflammatory and neuropathic pain, cognitive and behavioral deficits, and neuron death, and understand their roles in related pathways such as γ-butyric acid type A (GABA A ) receptor and cholinesterases using in vitro, in vivo and in silico methods. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test was used for cytotoxicity evaluation, hippocampal slice culture assay for neuroprotection, formalin test for acute and inflammatory pain, sciatic ligation for neuropathic pain, Morris water maze and open field locomotor tasks for cognitive and behavioral deficits, radioligand binding for GABA A receptor affinity, spectrophotometric methods for cholinesterase inhibition in vitro, and molecular docking in silico. The compounds were non-toxic to fibroblast cells. 5 k was neuroprotective against kainic acid-induced neuron death. 5i reduced pain response of mice in both the acute and the inflammatory phases. 5i improved survival upon status epilepticus. The compounds showed no affinity to GABA A receptor but inhibited acetylcholinesterase, 5 k also inhibited butyrylcholinesterase. The compounds were predicted to interact mainly with the peripheric anionic site of cholinesterase enzymes. The title compounds showed neuroprotective, analgesic, and cholinesterase inhibitory effects, thus they bear promise against certain co-morbidities of epilepsy with neurological insults., (© 2021 Wiley Periodicals, LLC.)

In this paper, we have prepared peripherally tetra-({6-[3-(diethylamino)phenoxy]hexyl}oxy substituted cobalt(II), copper(II), manganese(III) phthalocyanines ( 3, 4, 5) and their water-soluble derivatives ( 3a, 4a, 5a) . Then, in vitro α-glucosidase and cholinesterases inhibitory actions of the water-soluble 3a, 4a, 5a were examined using spectrophotometric methods. 4a had the highest inhibitory effects among the tested compounds against α-glucosidase due to IC 50 values. 4a and 5a had 40 fold higher inhibitory effects than the positive control. For cholinesterases, the compounds showed significant inhibitory actions that of galantamine which was used as a positive control. According to the SI value, 3a inhibited acetylcholinesterase enzyme selectively. In kinetic studies, 4a was a mixed inhibitor for α-glucosidase, 3a was a competitive inhibitor for AChE, and 4a was a mixed inhibitor for BuChE. The therapeutic potential of these compounds has been demonstrated by in vitro studies, but these data should be supported by further studies., (© TÜBİTAK.)

In this study, we tested tyrosinase and α-glucosidase effects of different extracts of Ziziphus jujuba fruits. The n -BuOH subextract inhibited both tyrosinase and α-glucosidase (IC 50  = 18.82 ± 1.13 and 25.03 ± 0.77 µg/mL, respectively) better than the positive controls kojic acid and acarbose (IC 50  = 58.26 ± 0.25 and 46.10 ± 2.3 µg/mL, respectively). Thus, the n -BuOH extract was selected for further phytochemical studies. Indole-3-lactic acid methylester, catechin, magnoflorine, kaempferol 3- O -α-rhamnopyranosyl-(1 → 6)-β-galactopyranoside, quercetin 3- O -α-rhamnopyranosyl-(1 → 6)-β-galactopyranoside, and procyanidin B4 were isolated from the extract. We tested α-glucosidase and tyrosinase inhibitory effects, as well as DNA nuclease effects of the isolated compounds. Procyanidin B4 exhibited the best activity against both tyrosinase and α-glucosidase (IC 50  = 60.25 ± 0.88 and 170.18 ± 5.60 µg/mL, respectively). The isolates did not show any nuclease effect at increasing concentrations. Molecular docking studies provided insights into inhibition mechanisms of the isolates against tyrosinase and α-glucosidase at the molecular level., Supplementary Information: The online version contains supplementary material available at 10.1007/s00217-021-03946-0., Competing Interests: Conflict of interestThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022.)

In this study, the synthesis of new monostyryl ( BDPY-2 ) and distyryl BODIPY dyes ( BDPY-4, BDPY-5 ) containing pyridine groups has been reported for the first time. The acetylcholinesterase from Electrophorus electricus (AChE), butyrylcholinesterase from equine serum (BuChE), α-glucosidase from Saccharomyces cerevisiae and DNA hydrolytic cleavage actions of BDPY-2 , BDPY-4 , BDPY-5 were investigated using various techniques. The results indicated that the compounds had varying inhibition properties against AChE, BuChE, and α-glucosidase. BDPY-4 was the most potent compound on AChE with IC 50 of 54.78 ± 4.51 µM, and Lineweaver-Burk plots indicated that the compound is bound to a site other than the active site as a noncompetitive inhibitor. The compound-protein binding experiment showed that BDPY-4 changed the microenvironment around AChE. On the other hand, the compounds showed lower α-glucosidase inhibition than the positive control. The DNA hydrolytic cleavage effects were not observed on supercoiled plasmid DNA in the presence of the compounds as compared to negative controls. These findings suggested that BDPY-4 might be a promising compound to treat Alzheimer's diseases., Competing Interests: CONFLICT OF INTEREST: none declared, (Copyright © 2021 The Author(s).)

Diabetes mellitus, a chronic disorder characterized by hyperglycemia, is considered a pandemic of modern times. α-Glucosidase inhibitors emerged as a promising class of antidiabetic drugs with better tolerability compared with its alternatives. Azoles, although widely preferred in drug design, have scarcely been investigated for their potential against α-glucosidase. In this study, we evaluated α-glucosidase inhibitory effects 20 azole derivatives selected out of an in-house collection via structure-based virtual screening (VS) with consensus scoring approach. Seven compounds were identified with better IC 50 values than acarbose (IC 50  = 68.18 ± 1.01 µM), a well-known α-glucosidase inhibitor drug, which meant 35% success for our VS methodology. Compound 52, 54, 56, 59, and 81 proved highly potent with IC 50 values in the range of 40-60 µM. According to the enzyme kinetics study, four of them were competitive, 56 was non-competitive inhibitor. Structure-activity relationships, quantum mechanical, and docking analyses showed that azole rings at ionized state may be key to the potency observed for the active compounds and modifications to shift the balance between the neutral and ionized states further to the latter could yield more potent derivatives., (© 2020 John Wiley & Sons A/S.)

Cancer has become an important public problem in worldwide since cancer incidence and mortality are growing rapidly. In this study, water soluble and non-aggregated silicon (IV) phthalocyanines and naphthalocyanines containing (3,5-bis{3-[3-(diethylamino)phenoxy]propoxy}phenyl)methoxy groups have been synthesized and characterized to investigate their anticancer potential. Their DNA binding/nuclease, topoisomerases inhibition were investigated using UV-Vis absorption, thermal denaturation and agarose gel electrophoresis. The in vitro cytotoxic properties of the compounds on human lung (A549), breast (BT-20), liver (SNU-398), prostate (DU-145), melanoma (SK-Mel 128) carcinoma and human fibroblast (HFC) normal cell lines were evaluated by using MTT assay. In order to determine the mechanism of cancer cell growth suppression, cell cycle analysis was carried out using flow cytometer on A549 cell line. The K b values of SiPc1a and SiNc2a were 6.85 ± (0.35) × 10 6 and 1.72 ± (0.16) × 10 4 M -1 and T m values of ct-DNA were calculated as 82.02 °C and 78.07 °C, respectively in the presence of both compounds. The Δ Tm values of SiPc1a and SiNc2a were calculated as 6.45 and 2.50 °C, respectively. The nuclease effects of SiPc1a and SiNc2a with supercoiled plasmid pBR322 DNA demonstrated that both compounds did not trigger any DNA nuclease effects at the lowest concentrations without irradiation whereas both compounds in the presence of activating agent (H 2 O 2 ) showed significant plasmid DNA nuclease actions under irradiation (22.5 J/cm 2 ). SiPc1a and SiNc2a inhibited to topoisomerase I on increasing concentrations whilst they had lower inhibition action toward topoisomerase II that of topoisomerase I. The in vitro cytotoxicity studies displayed that SiPc1a had the highest cytotoxic effects among the tested compounds against A549, SNU-398, SK-MEL128, DU-145, BT-20 and HFC cell lines with CC 50 values ranged from 0.49 to 2.99 µM. Furthermore, SiPc1a inhibited cell proliferation by cell cycle arrest in G 0 /G 1 phase. All of these results suggested that SiPc1a is a promising candidate as an anticancer agent., (Copyright © 2021 Elsevier Inc. All rights reserved.)

In this study, we investigated the in vitro potential of axially 1-morpholiniumpropan-2-ol disubstituted silicon (IV) phthalocyanine (SiPc) which was synthesized previously, on HCT-116 cells as a photodynamic therapy (PDT) agent. The singlet oxygen and photodegradation quantum yields of SiPc were calculated using UV-vis spectrophotometer. The cytotoxic and phototoxic effects of SiPc were evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. Annexin V-FITC/PI double staining kit, cell cycle kit, and mitochondria membrane potential (ΔΨm) assay kit with JC-1 were used to indicate the cell death pathway. Caspase-3 and β-catenin protein expressions were evaluated by western blotting. The singlet oxygen and photodegradation quantum yields of SiPc were calculated as 0.73 and 3.64 × 10 -4 in DMSO. The cell viability assays showed that IC 50 value of SiPc did not reach to 100 μM without irradiation. However, excellent phototoxicity was observed in the presence of SiPc upon light irradiation. The cells undergoing early/late apoptosis significantly increased in the presence SiPc at 5 μM upon light irradiation. Besides, the proportion of cells at S and G2/M phase increased. Moreover, mitochondria membrane potentials significantly decreased at 1 and 5 μM of SiPc with light irradiation. While caspase-3 expression increased, β-catenin expression significantly decreased on HCT-116 in the presence of SiPc (p < 0.01). The results indicated that the PDT could be related to apoptosis and Wnt/β-catenin signaling pathway. Based on our findings, SiPc exhibited a significant PDT effect on HCT-116 cells therefore, worthy of more detailed study., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Chrysosplenetin is a methoxyflavone with reported anti-cancer effect. We tested its cytotoxic effect on the MCF-7 breast cancer cell line, and determined its effect on DNA intercalation and on the activity of topoisomerases I and II. The compound inhibited proliferation MCF-7 with an IC 50 value of 0.29 μM. Chrysosplenetin did not initiate plasmid DNA cleavage but, in a concentration-dependent manner, protected plasmid DNA against damage induced by Fenton reagents. Furthermore, it possessed dual Topoisomerase I and II inhibitory properties. Especially, it inhibited topoisomerase II by 83-96% between the range 12.5-100 μM. In the light of these experimental findings, molecular docking studies were performed to understand binding mode, interactions and affinity of chrysosplenetin with DNA, and with topoisomerases I and II. These studies showed that of 4-chromone core and the hydroxyl and methoxy groups important for both intercalation with DNA and topoisomerase I and II inhibition., Competing Interests: Declaration of competing interest The authors have declared that these are no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Tyrosinase is a multifunctional copper-containing oxidase enzyme that catalyses the first steps in the formation of melanin pigments. Identification of tyrosinase inhibitors is of value for applications in cosmetics, medicine and agriculture., Objective: To develop an analytical method that allows identification of drug-like natural products that can be further developed as tyrosinase inhibitors. Results of in vitro and in silico studies will be compared in order to gain a deeper insight into the mechanism of action of enzyme inhibition., Method: Using an in vitro assay we tested tyrosinase inhibitor effects of five structurally related flavones, i.e. luteolin (1), eupafolin (2), genkwanin (3), nobiletin (4), and chrysosplenetin (5). The strongest inhibitors were further investigated in silico, using enzyme docking simulations., Results: All compounds tested showed modest tyrosinase inhibitory effect compared to the positive control, kojic acid. The polymethoxy flavones 4 and 5 exhibited the strongest tyrosinase inhibitory effect with the half maximal inhibitory concentration (IC 50 ) values of 131.92 ± 1.75 μM and 99.87 ± 2.38 μM respectively. According to kinetic analysis 2, 4 and 5 were competitive inhibitors, whereas 1 and 3 were non-competitive inhibitors of tyrosinase. Docking studies indicated that methoxy groups on 4 and 5 caused steric hindrance which prevented alternative binding modes in the tyrosinase; the methoxy groups on the B-ring of these flavones faced the catalytic site in the enzyme., Conclusions: The docking simulations nicely complemented the in vitro kinetic studies, opening the way for the development of predictive models for use in drug design., (© 2020 John Wiley & Sons, Ltd.)

In this study, novel silicon(iv) phthalocyanines axially disubstituted with bis[(4-{3-[3-(dimethylamino)phenoxy]propoxy}phenyl)methoxy] and bis[(4-{3-[3-(diethylamino)phenoxy]propoxy}phenyl)methoxy] groups and their quaternized derivatives were synthesized and characterized. Then, their supercoiled pBR322 plasmid DNA cleavage properties were investigated using agarose gel electrophoresis. The in vitro PDT effects of Si-3a and Si-4a were investigated using the MTT cell viability assay against HCT-116, A549 and SH-SY5Y cell lines. Si-3a and Si-4a did not show cleavage effects upon increasing concentrations in the dark but both compounds showed cleavage activities upon irradiation for 30 and 60 min, respectively. The MTT cell viability assay indicated that Si-4a had a cytotoxic effect in a concentration-dependent manner on the HCT-116 cell line but it did not show any statistical difference with regard to phototoxicity. Otherwise, Si-3a and Si-4a had significant phototoxic effects when compared to cytotoxic effects against A549 and SH-SY5Y. The results suggested that Si-3a and Si-4a showed better cell death against SH-SY5Y than other cell lines with irradiation.

In this study, BODIPY compounds (2, 3, 5 and 6) bearing 3,4-bis(3-pyridin-3-ylpropoxy)benzyl, 4-(3-pyridin-3-ylpropoxy)benzyl groups were synthesized for the first time and further functionalized in a Knoevenagel condensation reaction with 3,4-bis(3-pyridin-3-ylpropoxy)benzaldehyde and 4-(3-pyridin-3-ylpropoxy)benzaldehyde. The water soluble derivatives of BODIPY compounds (3a and 6a) were synthesized by treating BODIPY compounds 3 and 6 with excess iodomethane in DMF. The photochemical properties and DNA binding modes of 3a and 6a were determined using ct-DNA by UV-Vis spectrophotometer and viscometer. DNA cleavage and topoisomerases inhibition properties were studied DNA using agarose gel electrophoresis. Their topoisomerase inhibition mechanisms were investigated at molecular level and correlations with the in vitro results were searched for using molecular docking method. In addition, cytotoxicity and phototoxicity of both compounds were performed on colorectal cancer cells (HCT-116) using MTT assay for 24 h. Annexin V-FITC/PI test was performed to determine the cell death mechanism of 6a induced by irradiation. Finally, 6a-loaded liposomes (LP6a) and PLGA nanoparticles (NP6a) were prepared and their cytotoxic and phototoxic effects were evaluated by MTT assay. The results claimed that 6a had great potential as photosensitizer agent for colorectal cancer owing to its photochemical, DNA interaction and phototoxic properties., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Purpose: The aim of the present study was to evaluate the potential uroprotective effect of pantoprazole (PPZ) in a mouse model of cyclophosphamide (CP)-induced hemorrhagic cystitis (HC) due to its antioxidant and anti-inflammatory properties., Methods: Balb/c mice received a single intraperitoneal (i.p.) injection of CP (300 mg/kg) to induce HC. PPZ (20, 50, and 100 mg/kg/day;i.p.) was administered for 3 consecutive days before the induction of HC. Mesna (30 mg/kg;i.p.) was administered 20 min before, 4 and 8 h after CP injection to compare the protective effects of PPZ. After 24 h of HC induction, the bladders were removed for functional studies, biochemical analyses, and histopathological examination., Results: In vitro contractility studies demonstrated that CP-induced HC decreased the responsiveness of detrusor muscle strips to acetylcholine (ACh), which was reversed by PPZ pretreatment at all doses tested. However, mesna treatment was not able to improve responsiveness to ACh. Biochemical analyses showed that CP caused significant elevation of malondialdehyde (MDA), reduction of total glutathione (GSH), and increment of proinflammatory cytokine tumor necrosis factor-alpha (TNF-α) level, which were measured in bladder homogenates. PPZ pretreatment at three doses found to be effective in reducing the CP-induced elevation of MDA and TNF-α levels. The highest dose of PPZ (100 mg/kg) caused a significant increase in GSH level. CP induced severe HC with marked bladder edema and histological disturbances which were partially abolished by PPZ pretreatment., Conclusions: Our results indicate that PPZ pretreatment could attenuate CP-induced HC by interfering with oxidative stress and modulating proinflammatory cytokines.

In the present study, we aimed to identify the tyrosinase enzyme inhibitory potential of Vinca major L. extract and its secondary metabolites. The extract possessed remarkable tyrosinase enzyme inhibitory effect with IC 50 value of 20.39 ± 0.44 µg/mL compared to the positive control, kojic acid (IC 50 8.56 ± 0.17 µg/mL). Compounds 1 and 5 were the most potent isolates with IC 50 values of 32.41 ± 0.99 and 31.34 ± 0.75 µM, they were more potent than kojic acid (IC 50 : 60.25 ± 0.54 µM). Compound 2 also exhibited remarkable tyrosinase inhibition with an IC 50 value of 64.51 ± 1.29 µM. An enzyme kinetics analysis revealed that 1 was a mixed-type, 2 and 5 were noncompetitive inhibitors. Using molecular docking, we predicted binding affinity and interactions of the compounds, which were in good alignment with a pharmacophore hypothesis generated out of a number of known tyrosinase inhibitors. The modelling studies underlined crucial interactions with the copper ions and residues around them such as Asn260, His263, and Met280., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The volatile organic compounds (VOCs) of two Coronilla species ( Coronilla orientalis Miller and Coronilla varia L.) obtained by hydrodistillation (HD) and solid phase microextraction (SPME) techniques were identified by GC-FID/MS. The major compounds identified in the SPME extracts were limonene (43.4%) in Coronilla orientalis (C. orientalis), (Z)-β- ocimene and ( E )- β -ocimene (34.3% and 32.4%) in Coronilla varia (C. varia), whereas, the essential oils of C. orientalis and C. varia were rich with γ -terpinene (22.4%) and phytol (30.7%), respectively. In addition, acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), tyrosinase, α -glucosidase enzyme inhibitory, and radical scavenging activities (DPPH) of chloroform, ethyl acetate, methanol, and water extracts, and also essential oils obtained from C. orientalis and C. varia were investigated. The tyrosinase activity was studied at the doses of 25 µg/mL, 50 µg/mL and 100 µg/mL. Tyrosinase inhibition percentage was observed to increase by dose and methanol extracts of the both species were found to have the highest activity. Essential oils of the both species were found to have significant acetylcholinesterase and butyrylcholinesterase inhibition activities. α -Glucosidase enzyme inhibition of the ethyl acetate and water extracts of C. orientalis was determined as 80.11 ± 4.07% and 80.32 ± 3.47% at the 100 µg/mL concentration, respectively. Essential oils, chloroform, ethyl acetate, methanol, and water extracts were determined to have moderate DPPH radical scavenging activities.

Objectives: The scope of this study was to investigate the total phenolic, anthocyanin, and flavonoid contents and the biological properties of ethanol extract (EE), methanol extract (ME), and aqueous extract (AE) from Vaccinium arctostaphylos L., Materials and Methods: EE, ME, and AE of V. arctostaphylos were prepared. Various biological activities such as total phenolic, anthocyanin, and flavonoid contents, and antioxidant (2,2'-diphenyl-1-picrylhydrazyl ferrous ion-chelating, and ferric reducing antioxidant power assays), α-glucosidase inhibitory, anti-inflammatory, and DNA protective properties of these extracts were studied., Results: EE exhibited the highest total phenolic, anthocyanin, and flavonoid contents with 44.42±1.22 mg gallic acid equivalents/g dry weight, 8.46±0.49 mg/Cyaniding-3-glucoside equivalents/g dry weight, and 9.22±0.92 mg quercetin equivalents/g dry weight, respectively. The antioxidant activities of the extracts followed the order: EE>ME>AE. EE and ME inhibited α-glucosidase enzyme and their IC 50 values were 0.301±0.002 mg/mL and 0.477±0.003 mg/mL, respectively. In addition, EE and ME were determined as noncompetitive inhibitors with inhibitory constant ( K i ) values of 0.48±0.02 mg/mL and 0.46±0.01 mg/mL, respectively. EE in 100 and 300 mg/kg doses caused a significant reduction in formalin-induced edema in mice, demonstrating the anti-inflammatory effect of EE. In DNA protective studies, all of the extracts protected supercoiled plasmid pBR322 DNA against damage caused by Fenton's reagents due to their radical scavenging activities., Conclusion: Our results demonstrated that EE of V. arctostaphylos L . had strong antioxidant, anti-inflammatory, α-glucosidase inhibitory, and DNA protective effects, suggesting that it might be an effective medical plant to prevent or treat diseases associated with oxidative damage and inflammation., Competing Interests: Conflict of interest: There are no conflicts of interest among the authors., (©Copyright 2019 Turk J Pharm Sci, Published by Galenos Publishing House.)

Purpose: Hemorrhagic cystitis (HC) is defined as any types of acute or chronic inflammation of urinary bladder with several reasons. One of the most common causes of HC is cyclophosphamide (CYP), an effective antineoplastic agent, due to its urotoxic potential. Ambroxol (AMB) is a mucoactive drug that has been used for numerous respiratory diseases. Besides its mucolytic activity, AMB is a potent antioxidant and antiinflammatory agent that is becoming more attractive for the treatment of several oxidative/inflammatory disorders. The aim of this study was to evaluate the uroprotective potential of AMB in CYP-induced HC., Method: Male Balb/c mice were pretreated with AMB (30, 70, and 100 mg/kg) once a day for 3 consecutive days before HC induction with CYP (300 mg/kg). Mesna (30 mg/kg;i.p.), only drug in the management of CYP-induced HC, was administered 20 min before; 4 and 8 h after cystitis induction. The urinary bladders were harvested and evaluated in functional, biochemical, and histological studies., Results: CYP-induced HC markedly reduced acetylcholine (ACh)-induced contractions in detrusor strips and AMB at 100 mg/kg caused a significant increase in the responsiveness to ACh. Pretreatment with AMB prevented the elevation of malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α) level, reduction of total glutathione (GSH) that induced by CYP. However, treatment with AMB did not improve the bladder weight and some histological parameters., Conclusion: These results suggest that AMB pretreatment could improve CYP-induced HC via antioxidant and antiinflammatory activities.

Bark of Quercus coccifera is widely used in folk medicine. We tested tyrosinase and α-glucosidase inhibitory effects of Q. coccifera bark extract and isolated compounds from it. The extract inhibited tyrosinase with an IC 50 value of 75.13 ± 0.44 µg/mL. Among the isolated compounds, polydatin (6) showed potent tyrosinase inhibition compared to the positive control, kojic acid, with an IC 50 value of 4.05 ± 0.30 µg/mL. The Q. coccifera extract also inhibited α-glucosidase significantly with an IC 50 value of 3.26 ± 0.08 µg/mL. (-)-8-Chlorocatechin (5) was the most potent isolate, also more potent than the positive control, acarbose, with an IC 50 value of 43.60 ± 0.67 µg/mL. According to the kinetic analysis, 6 was a noncompetitive and 5 was a competitive inhibitor of tyrosinase, and 5 was a noncompetitive α-glucosidase inhibitor. In the light of these findings, we performed in silico molecular docking studies for 5 and 6 with QM/MM optimizations to predict their tyrosinase inhibition mechanisms at molecular level and search for correlations with the in vitro results. We found that the ionized form of 5 (5i) showed higher affinity and more stable binding to tyrosinase catalytic site than its neutral form, while 6 bound to the predicted allosteric sites of the enzyme better than the catalytic site., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Some Geranium species have been used to treat diabetes. To evaluate the scientific basis of this ethnopharmacological use, we aimed to isolate potent α-glucosidase inhibitory metabolites of Geranium asphodeloides Burm. through in vitro bioactivity-guided fractionation. All the tested extracts showed high α-glucosidase inhibitory effect compared to acarbose. Among the tested extracts, the ethyl acetate subextract showed the highest activity with an IC 50 value of 0.85 ± 0.01 µM. A hydrolysable tannin, 1,2,4-tri-O-galloyl-β-d-glucopyranose (1), and five flavonoid glycosides, kaempferol-3-O-α-rhamnopyranoside (2), kaempferol-3-O-α-arabinofuranoside (3), quercetin-3-O-β-glucopyranoside (4), quercetin-3-O-α-rhamnopyranoside (5), and quercetin-3-O-α-rhamnofuranoside (6), were isolated from the ethyl acetate subextract. Their structures were identified by 1D- and 2D-NMR experiments. 1 exhibited the highest α-glucosidase inhibitory effect, approximately 61 times more potent than positive control, acarbose, with an IC 50 value of 0.95 ± 0.07 µM. Also, 2 was more potent than acarbose. An enzyme kinetics analysis revealed that compounds 2, 3 and 4 were competitive, whereas 1 and 6 uncompetitive inhibitors. Molecular docking studies were performed to get insights into inhibition mechanisms of the isolated compounds in the light of the enzyme kinetic studies using various binding sites of the enzyme model., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Flavonoids are main polyphenolic groups widely distributed to fruits, vegetables and beverages we consumed daily. They exhibit many biological effects. We tested tyrosinase inhibitor potential of structurally related (1-9) flavonoids and found that all the tested materials possessed tyrosinase inhibitory effect compared to the positive control, kojic acid. 2 exhibited the strongest tyrosinase inhibitory effect with an IC 50 value of 40.94 ± 0.78 µM in a competitive manner. According to kinetic analysis 1, 4 and 7 were found to be competitive inhibitors, 3, 5, and 6 noncompetitive inhibitors of tyrosinase. According to the docking studies, A and C ring of the flavonoid structure, hydroxyl substituent at the 7th position, and hydroxyl substituents at para or para and meta position of ring B play key role for competitive inhibition of the enzyme., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Neolignans are a large group of polyphenols found in plants and exhibit a wide range of bioactivities including cytotoxicity, apoptosis inducer, antimalarial and antifungal effects, acetylcholinesterase, tyrosinase, and α-glucosidase inhibition. In this study we tested acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), tyrosinase, and α-glucosidase inhibitory effects of a rare neolignan, (-)-4-O-methyldehydrodiconiferyl alcohol 9'-O-β-glucopyranoside (1) in search for its new pharmaceutical effects. This compound exhibited good tyrosinase inhibition with an IC 50 value of 44.62 ± 3.99 μg/mL. Enzyme kinetics and molecular modelling studies were performed to provide insights into its tyrosinase inhibition mechanism., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

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 IC 50 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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: Crataegus species have been used as food and also in folk medicine for the treatment of various diseases. The present study aimed to make investigations on the biologic properties of different extracts prepared from Crataegus microphylla C. Koch, which was collected from Turkey., Materials and Methods: Dried leaf, stem bark, and fresh fruit samples of C. microphylla were separated and ethanol extract, acidified (0.5% HCl, pH: 2.5) ethanol extract, ethanol:water (1:1) extract, methanol extract, acidified (0.5% HCl, pH: 2.5) methanol extract, methanol:water (1:1) extract, water extract, and acidified (0.5% HCl, pH: 2.5) water extract were prepared for each. Various biologic effects such as the prevention of oxidative DNA damage, acetylcholinesterase, tyrosinase, α-glucosidase inhibition, and antioxidant effects with 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, PRAP, and FRAP assays of these extracts at different concentrations were studied., Results: Acidified methanol extract of stem barks exhibited the highest acetylcholinesterase and tyrosinase inhibitions among the other extracts with IC 50 values of 204.02±0.95 μg/mL and 37.30±0.27 μg/mL, respectively. Acidified ethanol extract of leaves was the most efficient extract against α-glucosidase, giving an IC 50 of 15.78±0.14 μg/mL. The IC 50 value of the acidified ethanol extract for DPPH was 9.89±0.09 µg/mL. Methanol extracts of leaves and stem barks at the dose of 125 µg/mL exhibited significant protective activity against DNA strand scission by hydroxyl radicals (.OH) on supercoiled pBR322 DNA., Conclusion: Acidified methanol or ethanol extracts prepared with stem bark and leaf from C. microphylla have potential antioxidant, hypoglycemic, and neuroprotective effects., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (©Copyright 2018 Turk J Pharm Sci, Published by Galenos Publishing House.)

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 IC 50 values of 1.06±0.02 and 0.93±0.01μg/ml respectively, compared to that of acarbose (IC 50 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 IC 50 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., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: 1,2,3-Triazole and its derivatives have important biological activities such as antimicrobial, anti-allergic, analgesic, anti-HIV, antiinflammatory, anticancer, antimalarial and antituberculosis. Other significant triazole derivatives are 1,2,4-triazoles which play a very important role in the medicinal chemistry due to the antiinflammatory, antimicrobial, antimigraine, anticancer, antimicrobial and antimycotic activities. In this study, we aimed to synthesize a new series of bis-1,2,3-triazole derivatives including 1,2,4-triazole to obtain more effective biological activities., Methods: In this study, a new series of bis-1,2,3-triazole compounds (9,10,11) were synthesized. Antimicrobial Activity: Disc diffusion method was used. Enzyme Inhibition: α-Glucosidase Inhibition was investigated. Antioxidant Activities: DPPH Radical Scavenging, Phosphomolybdenum- Reducing Antioxidant Power (PRAP) and Ferrous Ion-Chelating methods were used., Results: Compounds 9a, 9c, 9e, 9f, 10a, 10b, 10d, 11a, 11b and 11f showed significant antibacterial and antifungal activity against all the strains tested. Compound 9g exhibited the highest AChE inhibition. Compounds 10f, 11a and 11g showed remarkable activity against the BuChE enzyme. Compound 10f has the highest antioxidant activities., Conclusion: The compounds 9a, 9c, 9e, 9f, 10a, 10b, 10d, 11a, 11b and 11f exhibit the best antimicrobial activity against the bacteria and fungi C.albicans, Y. enterocolitica, E. coli, Candida albicans, Yersinia enterocolitica. Compound 9g exhibit the highest AChE inhibition with 72.67 ± 3.92% at 100 µg/mL. Compounds 10f, 11a and 11g showed remarkable activity against the BuChE enzyme compared to galantamine. Many of the compounds exhibited significant α-glucosidase inhibition activities. Compound 10f has the highest antioxidant activities (DPPH, PRAP, ferrous ionchelating) with 27.71 ± 0.85%, 0.689 ± 0.005, 42.07 ± 2.48 at 100 µg/mL, respectively., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

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, 1 H NMR, 13 C 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., (Copyright © 2017 Elsevier B.V. All rights reserved.)

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 IC 50 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., (Copyright © 2017 Elsevier B.V. All rights reserved.)

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., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

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 IC 50 values ranging from 37.86 ± 0.24 to 75.81 ± 2.49 μM. Among the compounds, 2j exhibited similar tyrosinase inhibitory effect (IC 50  = 37.86 ± 0.24 µM) to the positive control, kojic acid (IC 50  = 21.93 ± 0.11 µM). Kinetic studies revealed it to act as non-competitive tyrosinase inhibitor with a K i 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., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In this study, [2-(2-morpholin-4-ylethoxy)ethoxy] group substituted zinc(ii), manganese(iii) and copper(ii) phthalocyanines 2-4 and their water soluble derivatives 2a, 3a and 4a were synthesized and the interactions of compounds 2a, 3a and 4a with CT-DNA and supercoiled pBR322 plasmid DNA were investigated. The results of binding experiments showed that these compounds were able to interact with CT-DNA via intercalative mode with a strong binding affinity in the order 3a > 2a > 4a. DNA-photocleavage activities of compounds 2a, 3a and 4a were determined. These compounds cleaved supercoiled pBR322 plasmid DNA efficiently under irradiation at 650 nm for 2a and 4a, and at 750 nm for 3a. These compounds displayed remarkable inhibitory activities against topoisomerase I enzyme in a dose-dependent manner. All of these results suggest that these phthalocyanines might be suitable anticancer agents due to their strong binding affinities, significant cleavage activities and effective topoisomerase I inhibition.

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., (Copyright © 2016 Elsevier B.V. All rights reserved.)

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., (Copyright © 2015 Elsevier B.V. All rights reserved.)