Frankenia species are used in Asian traditional medicine, but just a few studies have reported the in vitro biological properties of Frankenia laevis L. [1], [2], [3]. Thus, this work explored this species as a potential source of bioactive compounds. Methanol and dichloromethane extracts were prepared from aerial organs (flowers, leaves and stems) and assessed for their chemical composition by HPLC-ESI-MS/MS. The extracts were evaluated for in vitro antioxidant capacity (DPPH and ABTS radical-scavenging, iron reducing power, copper and iron chelation), inhibitory effects on enzymes related with neurodegeneration (AChE and BuChE), Type-2 diabetes (α-glucosidase and α-amylase), hyperpigmentation/food oxidation (tyrosinase), and cytotoxicity towards human hepatocarcinoma (HepG2) cells. Fifty-one molecules were identified in the extracts, including derivatives of phenolic acids, lignans and flavonoids, monoterpenes, and hydroxylated derivatives of linoleic acid. The methanol extract was effective in DPPH and ABTS radical-scavenging (EC50 = 0.25 and 0.65 mg/mL, respectively), copper chelation (EC50 = 0.78 mg/mL), and iron reduction (EC50 = 0.51 mg/mL) activities, whereas the dichloromethane extract had high iron chelating ability (EC50 = 0.76 mg/mL). Both extracts inhibited α-glucosidase, especially the dichloromethane (EC50 = 0.52 mg/mL). This extract also exerted a significant selective cytotoxicity towards HepG2 cells (EC50 = 52.1 µg/mL, SI > 1.9). Generally, extracts from F. laevis aerial parts showed to be a promising source of natural compounds for pharmaceutical and/or food additives applications due to their high antioxidant, anti-diabetic, and cytotoxic properties.

The coupling of nitroxide and tertiary phosphane moieties offer unique opportunities in synthesis and catalysis as well as in biological effects. Surprisingly, no crystal structure report is found in CSD [1] for tertiary phosphane substituted pyrroline nitroxide. We first reported such structure [2] and synthesis of 3-(diphenylphosphino)-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-1-yloxyl radical, 1 , Fig.1., left. Structural data clearly indicate the expected nitroxide radical. Analysis of supramolecular structure gave interesting results (Fig. 1., right). A simple derivative had shown better antiproliferative effect on MDA-MB-231 and MCF-7 human breast cancer lines than MITO-CP indicating the potential of the compound for use in cancer therapy [3]. Moreover, inclusion of phosphane

Organophosphorus compounds occupy a significant position among the plethora of organic compounds, but a limited number of paramagnetic phosphorus compounds have been reported, including paramagnetic phosphonates. This paper describes the syntheses and further transformations of pyrroline and piperidine nitroxide phosphonates by well-established methods, such as the Pudovik, Arbuzov and Horner-Wadsworth-Emmons (HWE) reactions. The reaction of paramagnetic a-bromoketone produced a vinylphosphonate in the Perkow reaction. Paramagnetic a-hydroxyphosphonates could be subjected to oxidation, elimination and substitution reactions to produce various paramagnetic phosphonates. The synthesized paramagnetic phosphonates proved to be useful synthetic building blocks for carbon-carbon bond-forming reactions in the Horner-Wadsworth-Emmons olefination reactions. The unsaturated compounds achieved could be transformed into various substituted pyrroline nitroxides, proxyl nitroxides and paramagnetic polyaromatics. The Trolox® equivalent antioxidant capacity (TEAC) of new phosphonates was also screened, and tertiary a-hydroxyphosphonatate nitroxides exhibited remarkable antioxidant activity.

Syringodium isoetifolium (Asch.) Dandy (Family: Cymodoceaceae) is a seagrass growing in the oceans across the globe except in cold waters. This study investigated into the polyphenolic content, antioxidant [2,2-diphenyl-1-picrylhydrazyl(DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS), cupric reducing antioxidant capacity (CUPRAC), ferric reducing antioxidant power (FRAP), metal chelating, phosphomolybdenum)]and enzymatic properties [α-amylase, α-glucosidase, tyrosinase, acetylcholinesterase (AChE), butylcholinesterase (BChE)] of S. isoetifolium. Detailed phytochemical profiling was also conducted using Ultra Performance High-Pressure Liquid Chromatography (UHPLC) technique. The methanolic extract was found to possess greater amount of phenolic than flavonoid compounds. Antioxidant results showed that the extract was a better ABTS radical scavenger (9.56±0.40mg TE/g) compared to DPPH (5.39±0.09mg TE/g and exhibited good reducing potential with CUPRAC assay (18.66±0.46mg TE/g). In terms of enzymatic inhibition, strong activities were noted against tyrosinase (25.92±0.11mg KAE/g) in contrast to α-amylase, α-glucosidase and cholinesterase. Phytochemical data revealed the presence of 14 compounds with chicoric acid and caftaric acid among them. Docking the identified compounds, namely, caftaric acid, loliolide and Iso-loliolide at the active site of the tyrosinase enzyme has elucidated the binding affinity of these inhibitors and their interactions with the active site. Based on our findings, S. isoetifolium may be considered as a good natural antioxidant and clinical enzyme inhibitors that can be exploited in pharmaceutical/or cosmeceutical industries.

Background: Natural products and their derivatives are widely used to treat cancer and other diseases associated with ROS- and RNS-induced damages. Methods: A series of paramagnetic modified curcumin analogs and 3,5-diarylidene-piperidones (DAP) have been designed, synthesized, and characterized on their anti-proliferative and antioxidant activity. Results: Biological characterization of the new compounds supported the earlier results that incorporation of a nitroxide moiety or its precursor into curcumin or diarylidenylpiperidone (DAP) scaffolds resulted in anti-proliferative effect toward cancerous cell-lines in case of aryl hydroxy and/or methoxy substituent containing derivatives, suggesting their potential for targeted therapeutic applications. In case of basic side chain derivatives, nitroxide incorporation gave unambiguous results, however in tendency the more accessible DAP derivatives had stronger anti-proliferative effect. In most cases, the nitroxide incorporation increased the TEAC value (proton and electron donation capability) of DAP derivatives. Conclusions: Among the compounds synthesized and investigated the spin-labeled curcumin and 3,5-bis(4-hydroxy-3-methoxybenzylidene) piperidin-4-one derivatives were the most effective anti-proliferative and antioxidant derivatives.

4,4-Dimethylchromeno[4,3-d]selenadiazoles 8 with insecticide activities have been synthesized via oxidative ring closure of the corresponding semicarbazone derivatives 7 by treatment with selenium dioxide. Reaction of various alkoxy-2,2-dimethyl-2H-benzopyrans with phenylselenyl chloride was utilized to prepare different phenylselenyl- and 3-chloro precocene analogs.

Synthesis of paramagnetically modified deprenyl and oxotremorine is reported.Starting from 5and 6-membered 2,5-disubstituted nitrones 1, 6 or 4-phenyl-2,5,5-trimethyl-1H-pyrroline 1-oxide 11 deprenyl or oxotremorine like nitroxides were synthesized via Grignard reactions.The corresponding pre-nitroxides with propargylamine structure were achieved by reduction of nitroxides followed by methylation.

Novel 3-aryl-5-{4-[5-(2-hydroxyphenyl)-1-phenylpyrazolyl]}-2-pyrazolines 2a-g have been prepared by the treatment of 3-(3-aryl-3-oxopropenyl)chromen-4-ones

A simple solvent-free synthesis of 3-[1-(4-methylphenyl)-3-oxo-1,3,4,5,6,7-hexahydro-2H-isoindol-2-yl]propanoic acid 3 was achieved by fusion of cis-2-[(4-methylphenyl)carbonyl]cyclohexanecarboxylic acid 1 with 3-aminopropanoic acid 2. The structure of this new compound was confirmed by elemental analysis, IR, EI-MS, 1H-NMR and 13C-NMR spectral data.

New pyrroline nitroxides attached to a terminal acetylenic sulfone, a dibenzocyclooctyne or a cyclooctyne carboxylic acid were synthesized and tested in Cu-free click reactions to conjugate these new spin labels with 4-azido-TEMPO, azidophenylalanine and an azidophenylalanine-containing protein.

New derivatives of verapamil (1) modified with nitroxides and their precursors were synthesized and screened for reactive oxygen species (ROS)-scavenging activities. The basic structure was modified by changing the nitrile group to an amide or the methyl substituent on tertiary nitrogen with nitroxides and their reduced forms (hydroxylamine and secondary amines). Among the new verapamil derivatives compound 16B [Mohan, I. K.; Kahn, M.; Wisel, S.; Selvendiran, K.; Sridhar, A.; Carnes, C.A.; Bognár, B.; Kálai, T.; Hideg, K.; Kuppusamy, P. Am. J. Physiol. Heart Circ. Physiol. 2009, 296, 140], modified with hydroxylamine salt of 2,2,6,6-tetramethyl-1,2,3,6-tetrahydropyridine-1-yloxyl proved to be the best ROS scavenger in vitro and protected HSMC and CHO cells against H2O2 induced damage.

New, nitroxide-fluorophore acceptor-donor compounds were synthesized based on long wavelength (570-790 nm) emitting 9-diethylamino-5H-benzo[a]phenoxazin-5-one, 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene and metal-ligand complex fluorophores. The fluorophores and nitroxides were linked via a robust C=C bond. The steady-state spectral properties of the new donor-acceptor compounds and their diamagnetic (sterically hindered amine) derivatives were studied. Titration of nitroxides with ascorbic acid sodium salt to diamagnetic N-hydroxy compounds resulted in fluorescence enhancement The Ru-complex modified with nitroxide exhibited fluorescence increase and electron paramagnetic resonance band broadening upon B-deoxyribonucleic acid addition providing evidence of binding with B-deoxyribonucleic acid. (C) 2010 Elsevier Ltd. All rights reserved.

Starting from 3-bromo-4-formyl- or 3-bromo-4-cyano-2,2,5,5,-tetramethyl-2,5-dihydro-1H-pyrrol-1-yloxyl radicals, 2-substituted and 2,3-disubstituted 5H-selenolo[2,3-c]pyrrol-5-yloxyl radicals were synthesized. The 2-(bromomethyl)-substituted 5H-selenolo[2,3-c]pyrrol-5-yloxyl derivative was a key intermediate in the synthesis of a thiol specific methanethiosulfonate spin label reagent, a paramagnetic, selenophene ring-containing amino acid, and a new quinazolin-4(3H)-one derivative.

Hitherto unknown tetracyclic 1,5-benzothiazepines 9-16 have been synthesized by an acidcatalyzed reaction of exocyclic α,β,γ,δ-unsaturated ketones 1-8 and 2-aminothiophenol.Structures of all new compounds have been elucidated by microanalyses, 1 H-, 13 C-NMR, IR and mass spectroscopic measurements.

The Suzuki reaction of the pyrroline nitroxide, 3-bromo-4- formyl-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-1-yloxyl radical, with vinylboronic acids and subsequent Horner-Wadsworth-Emmons reaction followed by electocyclic reaction of the thus formed 1,3,5-triene and oxidation offers a new route for the synthesis of 5,6-disubstituted 1,1,3,3-tetramethylisoindolin-2-yloxyl radicals. The alternative Diels-Alder reaction pathway sometimes resulted in poor yields. Starting from 5-(ethoxycarbonyl)-1,1,3,3-tetramethyl-6-phenylisoindolin-2-yloxyl radical we obtained a spin-labeled fluorenone.

New exocyclic alpha,beta,gamma,delta-unsaturated ketones have been synthesized by the base-catalyzed reaction of chromanone, flavanone, their 1-thio analogues and trans-cinnamaldehydes. These unsaturated ketones were reacted with diazomethane at ca. 4 degrees C to afford spiro-1-pyrazolines in regioselective and stereospecific reaction. Structure and stereochemistry of all these new compounds have been elucidated by combined utilization of various spectroscopic, mainly NMR techniques.

4-Carboxamidobenzimidazoles were previously described as PARP inhibitor compounds. Here we report upon 4-carboxamido-1H-benzimidazoles substituted in the 2-position with nitroxides or their amine or hydroxylamine precursors. Among the new molecules, a highly active PARP inhibitor 4h (IC(50) = 14 nM) was identified with antioxidant/radical scavenger activity. We concluded that in most cases sterically hindered amines are better PARP inhibitors than their oxidized form and structural changes in the 2-substituted 4-carboxamido-1H-benzimidazoles (such as N-substitution or changing the position of the carboxamide group) were detrimental to PARP inhibition activity but not to antioxidant activity. These results indicate the advantages of combining an antioxidant nitroxide or nitroxide precursor with a PARP inhibitor molecule to decrease or eliminate the deleterious processes initiated by reactive oxygen and reactive nitrogen species (ROS and RNS). The radical scavenging capability of 4h was demonstrated by EPR study of urine collected after drug administration.

Hitherto unknown tetracyclic 1,5-benzothiazepines 9-16 have been synthesized by an acid-catalyzed reaction of exocyclic alpha,beta,gamma,delta-unsaturated ketones 1-8 and 2-aminothiophenol. Structures of all new compounds have been elucidated by microanalyses, H-1-, C-13-NMR, IR and mass spectroscopic measurements.

Hitherto unknown tetracyclic 1,5-benzothiazepines 9-16 have been synthesized by an acidcatalyzed reaction of exocyclic α,β,γ,δ-unsaturated ketones 1-8 and 2-aminothiophenol. Structures of all new compounds have been elucidated by microanalyses, H-, C-NMR, IR and mass spectroscopic measurements.

Diastereomeric mixtures of tricyclic 3‐styrylpyrazolines have been prepared by the reaction of 3‐cynnamylidenechroman‐4‐ones and their 1‐thio analogs with hydrazine in hot acetic acid or propionic acid solutions. The diastereomeric mixtures were separated by column chromatography to obtain the pure diastereomers. The elucidation of their structure and stereochemistry and complete 1H and 13C assignments have been performed by a combination of various one‐ and two‐dimensional NMR experiments. Copyright © 2008 John Wiley & Sons, Ltd.