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Aim: Synthesis of novel 2(2-hydroxyphenyl) pyrimidine/benzothiazole piperazinyl-substituted flavones end evaluate their antioxidant activity. Results: Six novel 2-(2-hydroxyphenyl) pyrimidine/benzothiazole-substituted flavones were synthesized, their structures were confirmed by elementary and spectral analyses. The compounds were evaluated for their in vitro antioxidant potency by employing various antioxidant assays. Conclusion: All tested compounds acted as scavengers of free radicals like hydroxyl (15–45%), 2,2-diphenyl-1-picrylhydrazyl• (17–48%) at 1.25 and 0.5 mM concentrations respectively. The total antioxidant status activity values of the compounds ranged from 234.1 to 464.1 μm trolox equivalent/g, the total antioxidant capacity – from 24.9 to 52.7 μm trolox equivalent per gram. Compounds incorporating the benzothiazole group on the piperazine ring were more effective antioxidants than those with the 2-(2-hydroxyphenyl) pyrimidine group.

Chromone, imidazolidinedione, thiohydantoin and 2,4-thiazolidinedione structures are known to be cytotoxic to cancer cells. In this study, biological activities of previously synthesized 18 chromonyl-2,4-thiazolidinediones/imidazolidinediones/thiohydantoins were tested by sulforhodamine B assay in five liver and one breast cancer cell lines. It was shown that a hybrid chromonyl thiohydantoin derivative C9 was able to significantly suppress the proliferation of the liver cancer cell lines which are very resistant to anticancer drugs. According to 50% growth inhibition concentrations of C9, well differentiated hepatocellular carcinoma cell line Huh7 and breast adenocarcinoma cell line Mcf7 cells are found to be highly sensitive to C9 with IC50 values between 4.9-5.2 mu M. Poorly differentiated human liver cancer cell line Snu449 is found to be the most resistant to C9. Further studies show that C9 causes morphological changes in Snu449 cells. However, it does not induce significant senescence response or cell cycle arrest. On the other hand, Huh7 cells are found to be arrested in G2/M phase of the cell cycle after 24 and 72 h treatment. In conclusion, a novel chromonyl thiohydantoin hybrid molecule effectively stops or slows down the proliferation of well-differentiated hepatocellular carcinoma cells that exist in primary tumors.

Medicinal plant extracts have been used for medical purposes throughout human history. In this study, khellin, having furochromone structure, which is obtained from a well-known traditional medicinal plant, was selected. A series of furochromonyl compounds (K1-K14) were synthesized for their anticancer activities. Furochromonyl compounds (K1-K14) were synthesized by Knoevenagel reaction of substituted 2,4-thiazolidinediones (Ia-j)/rhodanines (Ik-n) with khellin-2-carboxaldehyde (V), and their cytotoxicity was investigated in 22 cancer cell lines, which were originated from tissues such as the liver, breast, colon, and cervix. As the first step, two hepatocellular carcinoma cell lines Huh7 and PLC/PRF/5 (Alexander cells) were treated with 10 mu M of each compound for 72 h, and then sulforhodamine B assay was performed to analyze their anti-growth activities. Ethyl 2-(5-((4,9-dimethoxy-5-oxo-5H-furo[3,2-g]chromen-7-yl)methylene)-4-oxo-2-thioxothiazolidin-3-yl)acetate (K11) was found as the most cytotoxic compound of primary screening. Afterwards, 12 hepatocellular carcinoma, seven breast cancer, two colon cancer, and a cervical cancer cell lines were selected to test K11 for 72 h at multiple concentrations to determine 50% effective doses. Results showed that the 14 cell lines were affected by K11 quantities lower than 10 mu M. The structure of K11, which is particularly effective on breast cancers, can be used to slow down the progression of tumors. Furthermore, the discovery of more effective compounds can be carried out on the basis of this structure.

Purpose : A new series of thiazolyl-2,4-thiazolidinedione / rhodanine compounds T1-T23 was synthesized and tested for their anticancer activities. Hepatocellular carcinoma cell lines were chosen due to their strong drug resistance to test the new compounds. Methods : All compounds were synthesized via Knoevenagel Condensation reaction and thiazolidinedione ester compounds ( T3,T9,T15,T20 ) were hydrolyzed for obtaining the acidic compounds ( T6,T12,T17,T23 ). All compounds were firstly screened for their anticancer activity against two hepatocellular carcinoma (HCC) cell lines, Huh7 and Plc/Prf/5 (Plc) cell lines by sulforhodamine B assay. Further IC 50 values were calculated for three candidates ( T4 , T15 , T21 ) in five different HCC (Huh7, Plc, Snu449, HepG2, Hep3B) and one breast cancer (Mcf7) cell line. Results : Compounds T4 , T15 , T21 had very strong anticancer effects even though their 10 µM concentration in Huh7 cell line. According to IC 50 values, T21 was the most effective compound with IC 50 values in a range from 2 to 16 µM in 6 cancer cell lines. In terms of cytotoxicity T21 mostly affected Huh7 and interestingly it was less effective against Plc. Conclusions : Considering these results it can be suggested that compounds T4 , T15 and T21 may lead to the development of more potent anticancer drugs in the future. This article is open to POST-PUBLICATION REVIEW . Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

Cancer is an extensive and complicated family of malignancies that can affect virtually every part of the body. It is reported that over 1.2 million new cases are diagnosed every year. In most of the patients, meaningful clinical results cannot be achieved by the currently available cancer therapies and we still need efficient probes as drugs to cure. Natural products have long been a source of antitumor drugs and new natural products are reasonable to be expected as promising leads for antitumor drug discovery. Among natural products, flavonoids are a group of polyphenolic compounds present in plants and they have attracted considerable attention by virtue of their diverse and interesting biological activities such as anti-inflammatory, neuroprotection and antitumor activity. In this study, we describe the synthesis of a new series of N-substituted 6-methoxyflavonyl piperazine derivatives (Formula) with the aim of testing their cytotoxic and anticancer activities. The structural evaluation of the synthesized compounds was based on the 1H NMR, Mass and elementary analysis data. The synthesized compounds are under investigation for their anticancer activities.

Fifteen chromonylrhodamine derivatives (CRs) were synthesized and the antioxidant activity levels were evaluated for the first time. The antioxidant activity potencies of these chromone derivatives were evaluated towards superoxide anion radicals, hydroxyl radicals and 2,2-diphenyl-1-picrylhydrazyl radicals. Also, the total antioxidant capacity of the tested compounds was measured using the ferric-ferrozine assay. The antioxidant activities were investigated using a chemiluminescence (CL) assay, spectrophotometry measurements, direct electron paramagnetic resonance (EPR) and the EPR spin-trapping technique. The 5,5-dimethyl- 1-pyrroline-1-oxide (DMPO) was applied as spin trap. Eleven of the 15 chromone compounds exhibited a decrease in the CL accompanying the superoxide anion radical produced in anhydrous dimethylsulfoxide (DMSO), ranging from 71–94% at concentration of 1 mmol /L; four of these compounds enhanced light emission in the range 231–672%. Similarly, these compounds caused 28–58% inhibition in the intensity of the DMPO-OOH radical EPR signal and the DMPO-OH radical (from 12–48%). Furthermore, three of these compounds showed very good antioxidant response towards the DPPH radical (EC50: 0.51–0.56 µmol/L) and the high reduction potentials. These findings demonstrate that the chromone compounds tested may be considered as effective free radicals scavengers, a finding that is of great pharmacological importance. Copyright © 2014 John Wiley & Sons, Ltd.

A series of flavonyl-2,4-thiazolidinedione, imidazolidinedione and rhodanine derivatives were tested for their antioxidant activity as scavengers of oxygen free radicals. Free radical scavenging activities, including superoxide anion radical O2•, hydroxyl radical (HO(•)) and 2,2'-diphenyl-1-picrylhydrazyl free radical have been evaluated using chemiluminescence, electron paramagnetic resonance and spin trapping with 5,5-dimethyl-1-pyrroline-1-oxide as a spin trap. Potassium superoxide in dimethylsulfoxide and 18-crown-6 ether were used for the production of O2•. Hydroxyl radical was generated using the Fenton reaction. Ten of the eleven examined compounds exhibited decrease in chemiluminescence, but there were large differences in the decrease, ranging from 16% to 89%; also, two of these compounds increased light emission by about 200%. On the contrary, all compounds tested exhibited 30-68% scavenging HO(•) and 25-96% scavenging the DPPH(•) radical respectively. Possible mechanisms are proposed to explain the results.

Recent reviews evidence that the naturally occurring compounds containing the chromone skeleton exhibit antiradical activities, providing protection against oxidative stress. The antioxidant activities of 13 new synthesized chromonyl-2,4-thiazolidinediones, chromonyl-2,4-imidazolidinediones and chromonyl-2-thioxoimidzolidine-4-ones were evaluated using in vitro antioxidant assays, including superoxide anion radical (), hydroxyl radical (), 2,2-diphenyl-1-picryl-hydrazyl free radical (DPPH•) scavenging capacity and total antioxidant capacity ferric ion reducing activity. Superoxide anion radical was produced using potassium superoxide/18-crown-6-ether dissolved in dimethylsulfoxide, and the Fenton-like reaction (Fe(II) + H2O2) was a generator of hydroxyl radicals. Chemiluminescence, spectrophotometry, electron paramagnetic resonance (EPR) and 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as the spin trap were the measurement techniques. The results showed that the majority of the chromone derivatives tested showed a strong scavenging effect towards free radicals, similar to the chemiluminescence reaction with superoxide anion radical with a high activity, inhibition of the DMPO-OOH radical EPR signal (24–58%), the DMPO-OH radical EPR signal (4–75%) and DPPH radical EPR signal (6–100%) at 1 mmol/L. Several of the examined compounds exhibited the high reduction potentials. The results obtained show that the new synthesized chromone derivatives may directly scavenger reactive oxygen species and thus may play a protective role against oxidative damage. Copyright © 2014 John Wiley & Sons, Ltd.

The antioxidant properties of 11 new synthesized chromonyl-2,4-thiazolidinediones and chromonyl-2,4-imidazolidinediones (CBs) were investigated. The antioxidant activities and mechanisms of the CBs interaction with reactive oxygen species (ROS) were clarified using various in vitro antioxidant assay methods including superoxide anion radical (O2(•-)), hydroxyl radical (HO(•)), 1,1-diphenyl-2-picryl-hydrazyl free radical (DPPH(•)) scavenging activity and the iron (II)-ferrozine complex formation. The potassium superoxide/18-crown-6 ether dissolved in dimethylsulfoxide (DMSO) was applied as a source of superoxide anion radical. Hydroxyl radicals were produced in the Fenton-like reaction Fe(II)+H2O2. Chemiluminescence, spectrophotometry, and electron paramagnetic resonance (EPR) spectroscopy using 5,5-dimethyl-1-pyrroline-1-oxide (DMPO) as spin trap were applied as the measurement techniques. The CBs examined that exhibited good free radical scavenging activity also showed strong total antioxidant power capacity. Possible mechanisms of antioxidation are proposed to explain the differences in the experimental results between the chromone derivatives with imidazolidine-2,4-dione ring and those with thiazolidine-2,4-dione ring. In conclusion, some of the new CBs are promising to be applied as inhibitors of free radicals.

The benefits of antioxidants on human health are usually ascribed to their potential ability to remove reactive oxygen species providing protection against oxidative stress. In this paper the free radicals scavenging activities of nine 6-methyl 3-chromonyl derivatives (CMs) were evaluated for the first time by the chemiluminescence, electron paramagnetic resonance, spin trapping and 2,2-diphenyl-1-picrylhydrazyl (DPPH•) methods. The total antioxidant capacity was also measured using a ferric-ferrozine reagent. Compounds having a hydrogen atom at the N3-position of the β-ring were effective in quenching CL resulted from the KO2/18-crown-6-ether system (a source of superoxide anion radical, ) in a dose-dependent manner over the range of 0.05–1 mmol/L [IC50 ranged from 0.353 (0.04) to 0.668 (0.05) mmol/L]. The examined compounds exhibited a significant scavenging effect towards hydroxyl radicals (HO• HO•), produced by the Fenton reaction, and this ranged from 24.0% to 61.0%, at the concentration of 2.5 mmol/L. Furthermore, the compounds examined were also found to inhibit DPPH• and this ranged from 51.9% to 97.4% at the same concentration. In addition, the use of the total antioxidant capacity assay confirmed that CM compounds are able to act as reductants. According to the present study, CM compounds showed effective in vitro free radical scavenging activity and may be considered as potential therapeutics to control diseases of oxidative stress-related etiology. Copyright © 2013 John Wiley & Sons, Ltd.

Free radical activity towards superoxide anion radical (), hydroxyl radical (HO•) and 2,2-diphenyl-1-picrylhydrazyl (DPPH•) of a series of novel thiazolidine-2,4-dione derivatives (TSs) was examined using chemiluminescence, electron paramagnetic resonance (EPR) and EPR spin trapping techniques. 5,5-Dimethyl-1-pyrroline-N-oxide (DMPO) was applied as the spin trap. Superoxide radical was produced in the potassium superoxide/18-crown-6 ether dissolved in dimethyl sulfoxide. Hydroxyl radical was generated in the Fenton reaction (Fe(II) + H2O2. It was found that TSs showed a slight scavenging effect (15–38% reduction at 2.5 mmol/L concentration) of the DPPH radical and a high scavenging effect of (41–88%). The tested compounds showed inhibition of HO• -dependent DMPO-OH spin adduct formation (the amplitude of EPR signal decrease ranged from 20 to 76% at 2.5 mmol/L concentration. Our findings present new group compounds of relatively high reactivity towards free radicals. Copyright © 2012 John Wiley & Sons, Ltd.

A series of chromonyl-2,4-thiazolidinediones/imidazolidinediones/2-thioxo-imidazolidine-4-ones (IIIa-i, IVa-i) was prepared by Knoevenagel reaction of 2,4-thiazolidinedione/2,4-imidazolidinedione/2-thioxo-imidazolidine-4- one (IIa-c) with 2/3-formyl chromone (Ia-b) and then alkylation with methyl/ethyl iodide. The prepared compounds were tested for their insulinotropic activities in INS-1 cells. Compounds iVb and iVc (at lower concentration, 1 mu g/mL) were able to increase insulin release in the presence of 5.6 mmol/L glucose." should be written as "Compounds IVb and IVc (at lower concentration, 1 mu g/mL) and also IIId and IIIg (at higher concentration) were able to increase insulin release in the presence of 5.6 mmol/L glucose. Compounds iVb and iVc (at lower concentration, 1 mu g/mL) were able to increase insulin release in the presence of 5.6 mmol/L glucose.

In this study, a series of 2,4-dichlorothiazolyl thiazolidine-2,4-dione (Ia-f) and 4-chloro-2-benzylsulfanylthiazolyl-thiazolidine-2,4-dione derivatives (IIa-f) were tested for their antioxidant properties by determining their effects on superoxide anion formation, and the 2,2-diphenyl-1-picrylhydrazyl (DPPH) stable free radical. Compound Ic showed the best superoxide anion scavenging activity at the 10−3 M and 10−4 M concentrations. The compounds (Ia-f and IIa-f) had the strong DPPH radical scavenger capacity at the 10−3 M concentration. Compound Ib, Id, and Ie showed similar activity to butylated hydroxytoluene (BHT) at 10−3 M and 10−4 M concentrations.

The synthesis and biological activity of a new series of 2-{3-[substituted benzylamino-methyl)-phenyl]-4H-benzopyrane-4-one (IVa-e) and N-substituted benzyl-N-[3-(4-oxo-4H-benzopyrane-2-yl)benzyl]-3-phenyl-acrylamide (Va-e) derivatives are reported. The synthesized compounds were tested in vitro for antifungal and antibacterial activities. Compound IVa showed the best antifungal activity compared with miconazole (CAS 22916-47-8). Compound IVc indicated the best antibacterial activity compared with the control drug ampicillin (CAS 69-53-4).

In diabetes, increased flux through the polyol pathway has been implicated in the development of diabetic complications such as cataract, retinopathy, neuropathy, and nephropathy. Aldose reductase (AR) appears to be the key factor in the reduction of glucose to sorbitol. Aldose reductase inhibitors have been found to prevent sorbitol accumulation in tissues. A series of thiazolyl-2,4-thiazolidinediones was prepared by Knoevenagel reaction of substituted benzyl-2,4-thiazolidinediones with chlorothiazolecarbaldehydes and were evaluated for their ability to inhibit rat kidney AR by an in vitro spectrophotometric assay. Results showed that compounds containing piperidine at the C-2 position of thiazole ring showed better inhibitory activity than thiazole compounds having 4-chlorobenzylsulfanyl at the same position.

UNLUSOY, Meltem CEYLAN/0000-0002-7070-8181 WOS: 000236470100227 In the title compound, C14H9NO4S, the benzopyran and thiazolidine ring systems are each planar. The thiazolidine ring makes a dihedral angle of 3.84 (4)degrees with the benzopyran ring system. The molecular structure is stabilized by intramolecular C-H center dot center dot center dot O interactions.

In the title mol­ecule, C20H12ClNO4S, the benzopyran ring system and the thia­zolidine ring are planar. The dihedral angle between the chloro­benzyl and thia­zolidine rings is 74.42 (8)°. The crystal structure is stabilized by intermolecular C—H⋯O hydrogen bonds.

Kazak, Canan/0000-0003-2475-8775; Bozdag Dundar, Oya/0000-0002-2240-8854; UNLUSOY, Meltem CEYLAN/0000-0002-7070-8181 WOS: 000326745800010 PubMed: 23057864 Numerous compounds have been prepared in order to improve the pharmacological profile of insulinotropic activities. In the present paper, we report the synthesis and the in vitro insulin releasing activity of the 6-methyl-chromonyl-2,4-thiazolidinediones (IIIa-c, IVa-c, Va-c). Compounds IIIb, IIIc, IVa-c, Va and Vc (at lower concentration; 0.001 mg/mL) were able to increase insulin release in the presence of 5.6 mmol/L glucose. In this series, the most potent compound is IVa having methyl group at N3 position of TZD ring. Research Organization of Ankara University, TurkeyAnkara University [09B3336003] This work was supported by Research Organization of Ankara University, Turkey (No: 09B3336003).

The scavenging effects of eighteen thiazolyl thiazolidine-2,4-dione compounds (TTCs) on superoxide radical , hydroxyl radical HO•, and 1,1-diphenyl-2-picrylhydrazyl (DPPH•) radical were evaluated by the chemiluminescence technique, electron spin resonance spectrometry (ESR) and visible spectrophotometry, respectively. The examined compounds were shown to have 27–59% scavenging ability, 19–69% HO• scavenging activity and 2–32% DPPH• scavenging ability. This property of the tested compound seems to be important in the prevention of various diseases of free radicals etiology. Copyright © 2009 John Wiley & Sons, Ltd.

A series of thiazolyl-2,4-thiazolidine-diones (Ia-f, IIa-f and IIIa-f) was prepared by Knoevenagel reaction of substituted benzyl-2,4-thiazolidinediones (4a-f) with chlorothiazolecarbaldehydes (2, 3a-b). The prepared compounds were tested for their insulinotropic activities in INS-1 cells.. A significant insulinotropic effect was seen with compounds If and IIa.

UNLUSOY, Meltem CEYLAN/0000-0002-7070-8181 WOS: 000243191000195 The molecule of the title compound, C15H12N2O4, is planar, with a dihedral angle of 0.97(4)degrees between the planes of the five-membered imidazolidine and benzopyran ring systems. The crystal structure is stabilized by C-H center dot center dot center dot O and N-H center dot center dot center dot O hydrogen-bonding interactions.

A new series of furochromone-2,4-thiazolidinedione derivatives (VIIa-h) was prepared by Knoevenagel reaction of substituted-2,4-thiazolidinediones (VIa-h) with Khellin-2-carboxaldehyde (IV). The prepared compounds were tested for their insulinotropic activities in INS-1 cells. Compounds VIId and VIIf (at lower concentration; 1 microgram/ml) were able to increase insulin release in the presence of 5.6 mmol/l glucose. Both these compounds (VIId and VIIf) and VIIg increased glucose uptake in NIH-3T3 cells. Thus these 3 compounds should be tested for antidiabetic effects in vivo.

The structure of the title compound, C17H16N2O3S, was prepared by the reaction of chromone-3-carboxaldehyde with 2-thioxo-imidazolidine-4-one and ethyl iodide. The five-membered imidazolidine ring is in a planar conformation with a maximum deviation of 0.013(1)A, and making a dihedral angle of 5.36(5)° with the benzopyran ring system. The crystal structure is stabilized by intra and intermolecular hydrogen-bond interactions.

In this study, a series of phenylefhylsul-fanyl-1,3-thiazolo-thiazolidine-2,4-dione derivatives (VII a –f, VIII a–f) and 5-methyl-[1,2,4] triazolyl-sulfanyl-1,3-fhia-zolo-thiazolidine-2,4-dione derivatives (IXa–f, Xa–f) were synthesized and evaluated for their antibacterial and antifungal activities against S. aureus (ATCC 25923), methicillin resistant S. aureus (MRSA ATCC 43300), B. subtilis (ATCC 6633), E. coli (ATCC 23556) and C. albicans (ATCC10145). All the compounds were found active against used bacteria.