Possible antagonism of (Z)‐2‐hexenyl (E)‐3‐hexenoate against the attractiveness of (E)‐2‐hexenyl (Z)‐3‐hexenoate to Ooencyrtus nezarae (Hymenoptera: Encyrtidae)

Ooencyrtus nezarae (Hymenoptera: Encyrtidae) is an egg parasitoid of bean bug Riptortus pedestris (Hemiptera: Alydidae) which is a major pest of beans. Females of O. nezarae are attracted to (E)‐2‐hexenyl (Z)‐3‐hexenoate (EZ), one of the components of aggregation pheromone of R. pedestris. Effects of three isomers (ZE, EE and ZZ) of EZ on the attractiveness of O. nezarae were tested using electroantennography (EAG) and field bioassays. EAG analyses revealed that the response of O. nezarae to ZE was significantly higher than those to air, hexane and two other isomers, even though the response was lower than that to EZ. ZE affected the attractiveness of EZ dose‐dependently in the field. Addition of ZE (100 mg) to EZ (10 mg) caused a significant reduction in the catches of O. nezarae females. Single or binary addition of two other isomers (EE and ZZ) to EZ could not decrease or increase significantly the number of O. nezarae catches of EZ. Even though addition of ZZ (10, 50 or 100 mg) to EZ (10 mg) caused dose‐dependent reduction in the number of O. nezarae female catches, the reductions were not significantly different from that of EZ. EZ and its three isomers were not attractive to O. nezarae males at all.     

Syntheses and β‐adrenergic binding affinities of (R)‐ and (S)‐fluoronaphthyloxypropanolamines

The β‐adrenergic receptors mediate several physiological processes including heart rate (β₁), bronchodilation (β₂), and lipolysis (β₃). Therefore, selectivity is important for a possible therapeutic agent acting via these receptors. Aryloxypropanolamines are β‐receptor agonists or antagonists, depending on the aryl group and its substituents. We therefore hypothesized that fluorine substitution on the aromatic ring in this class could lead to significant biological effects because of the unique chemical characteristics of fluorine. Because the target compound has a chiral center, we set out to synthesize the two enantiomers so that effects of stereochemistry on biological activity could be evaluated. Syntheses of the enantiomers were performed starting with commercially available fluoronaphthalene and subsequent use of the chiral synthon (2R)‐ or (2S)‐glycidyl 3‐nitrobenzenesulfonate, depending on the desired enantiomer. High‐pressure liquid chromatography (HPLC) methods were used to characterize %ee. Each enantiomer was synthesized. They exhibited nanomolar binding activities on β‐adrenergic receptors. The (S)‐enantiomer was found to be up to 310 times more potent than the (R). It was also found to be about five‐fold more selective for β₂‐ than for β₁‐receptors. The current report demonstrates the importance of stereochemistry for the fluoroaromatic β‐receptor ligands. Chirality 11:144–148, 1999. © 1999 Wiley‐Liss, Inc.     

Synthesis and Antioxidant Activity of 3‐(Pyridin‐2‐ylmethyl)‐1,3‐thiazinan(thiazolidin)‐4‐ones

The antioxidant properties of two series of thiazolidinones and thiazinanones were reported. The novel six‐membered thiazinanones were synthesized from the efficient multicomponent reaction of 2‐picolylamine (2‐aminomethylpyridine), arenaldehydes, and the 3‐mercaptopropionic acid in moderate to excellent yields. These novel compounds were fully identified and characterized by NMR and GC‐MS techniques. In vitro antioxidant activities of all compounds were evaluated by 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) and 2,2′‐azinobis‐3‐ethylbenzothiazoline‐6‐sulfonic acid (ABTS) tests. The antioxidant assays of thiobarbituric acid reactive species and total thiol content levels in the cerebral cortex and liver of rats were also performed. Thiazinanone 5a showed the best radical scavenging activity in DPPH and ABTS tests, as well as reduced lipid peroxidation and increased total thiol group in biological systems. Altogether, the results may be considered a good starting point for the discovery of a new radical scavenger.     

Stereoselective Synthesis of (3R)‐3‐Alkyl‐4,1‐Benzoxazepine‐2,5‐Diones

Novel 3‐alkyl‐4,1‐benzoxazepine‐2,5‐diones were synthesized in good ee exploiting the chiral pool methodology, an economical way of asymmetric synthesis. Various anthranilic acids are coupled with different α‐haloacids to afford N‐acylated anthranilic acid intermediates which undergo cyclization to (3R)‐3‐alkyl‐4,1‐benzoxazepines‐2,5‐diones. Chirality 25:865–870, 2013. © 2013 Wiley Periodicals, Inc.     

Fluorescence modulation of 1,7‐bis(4‐hydroxy‐3‐methoxyphenyl)‐1,6‐heptadiene‐3,5‐dione by silver nanoparticles and its possible analytical application

The effects of silver nanoparticles on the photophysical properties of 1,7‐bis(4‐hydroxy‐3‐methoxyphenyl)‐1,6‐heptadiene‐3,5‐dione, popularly known as curcumin, have been investigated using optical absorption and fluorescence techniques. Although absorption spectroscopy suggests a ground‐state complex formation, fluorescence quenching data confirms a simultaneous static and dynamic quenching, inferring ground as well as excited‐state complex formation. The recovery of fluorescence quenching of the curcumin–silver nanoparticle complex in the presence of ascorbic acid or uric acid emphasizes a strong interaction between the silver nanoparticles and ascorbic acid/uric acid, suggesting that fluorescence recovery after the quenching of curcumin–silver nanoparticle complexes has potential for ascorbic acid or uric acid assay development. Copyright © 2011 John Wiley & Sons, Ltd.     

Synthesis and Biological Evaluation of Novel 1‐(4‐(Hydroxy(1‐oxo‐1,3‐dihydro‐2H‐inden‐2‐ylidene)methyl)phenyl)‐3‐phenylurea Derivatives

A series of novel phenylurea containing 2‐benzoylindan‐1‐one derivatives 3a  –  3j were synthesized from the reaction of phenylurea‐substituted acetophenones 1a  –  1j with phthalaldehyde 2 under mild reaction conditions in good yields. All synthesized compounds were characterized by spectroscopic methods. The obtained compounds ( 3a  –  3j ) were evaluated for anticancer activity against HeLa and C6 cell lines. Antiproliferative activity was determined by the BrdU proliferation ELISA assay, 3f and 3g were found to be most active compounds. The compounds were also screened for antimicrobial activity and all compounds showed remarkable activity against used microorganisms.     

Syntheses and Antitumor Evaluation of C(6)‐Isobutyl‐ and C(6)‐Isobutenyl‐Substituted Pyrimidines,and Dihydropyrrolo[1,2‐c]pyrimidine‐1,3‐diones

A growing body of evidence supports that pyrimidine derivatives, in which the sugar residues have been replaced by acyclic side chains, might be developed as promising anticancer agents that interfere with tumor cell proliferation, survival, and metastatic formation. In this work, we prepared novel pyrimidines bearing i‐Bu (i.e., 3, 4 , and 7 – 9 ) and isobutenyl (i.e., 5 and 10 ) side chains at C(6) and examined their in vitro effects on tumor cell lines. The dihydropyrrolo[1,2‐c]pyrimidine‐1,3‐diones 6 and 11 were obtained as products of intramolecular cyclization, which occurred during the removal of Bn in 5 or MeO protecting groups in 10 . Fluorination of 3 with diethylaminosulfur trifluoride (DAST) and then dehydrohalogenation of the resulting fluorinated derivative 4 afforded 6‐isobut‐2′‐enyl pyrimidine derivative 5 with a C(2′)C(3′) bond. For the preparation of 6‐isobut‐1′‐en‐1‐yl pyrimidine 10 , a synthetic strategy involving acetylation of the 1,3‐diols was applied. Antitumor evaluation of compounds 3 – 11 showed that 2,4‐dimethoxypyrimidine containing 6‐[(1,3‐dibenzyloxy)‐2‐hydroxy]methyl side chain, 3 , exerted a strong antiproliferative effect on the studied tumor cell lines. Additionally, it was shown that the mechanism of antiproliferative effect of 3 in HeLa cells include early G2/M arrest and apoptosis, as well as a p53‐independent S‐phase arrest upon prolonged treatment.     

Human α‐amino‐β‐carboxymuconate‐ε‐semialdehyde decarboxylase (ACMSD): A structural and mechanistic unveiling

Human α‐amino‐β‐carboxymuconate‐ε‐semialdehyde decarboxylase determines the fate of tryptophan metabolites in the kynurenine pathway by controlling the quinolinate levels for de novo nicotinamide adenine dinucleotide biosynthesis. The unstable nature of its substrate has made gaining insight into its reaction mechanism difficult. Our electron paramagnetic resonance (EPR) spectroscopic study on the Cu‐substituted human enzyme suggests that the native substrate does not directly ligate to the metal ion. Substrate binding did not result in a change of either the hyperfine structure or the super‐hyperfine structure of the EPR spectrum. We also determined the crystal structure of the human enzyme in its native catalytically active state (at 1.99 Å resolution), a substrate analogue‐bound form (2.50 Å resolution), and a selected active site mutant form with one of the putative substrate binding residues altered (2.32 Å resolution). These structures illustrate that each asymmetric unit contains three pairs of dimers. Consistent with the EPR findings, the ligand‐bound complex structure shows that the substrate analogue does not directly coordinate to the metal ion but is bound to the active site by two arginine residues through noncovalent interactions. Proteins 2015; 83:178–187. © 2014 Wiley Periodicals, Inc.     

Synthesis and optical resolution of 1‐[(3‐carboxy‐1,1′‐biphenyl)‐2‐yl]‐1H‐pyrrole‐2‐carboxylic acid

Site selective mono‐ and dimetalation methods have been developed for the functionalization of 1‐[(1,1′‐biphenyl)‐2‐yl]‐1H‐pyrrole. Optical resolution of the prepared 1‐[(3‐carboxy‐1,1′‐biphenyl)‐2‐yl]pyrrole‐2‐carboxylic acid provided new atropisomeric 1‐arylpyrrole derivatives. The absolute configuration of the pure dicarboxylic acid enantiomers was determined by single crystal X‐ray diffraction and CD spectroscopy. Chirality 2009. © 2009 Wiley‐Liss, Inc.     

Posttranslational oxidative modification of (R)‐2‐(2,4‐dichlorophenoxy)propionate/α‐ketoglutarate‐dependent dioxygenases (RdpA) leads to improved degradation of 2,4‐dichlorophenoxyacetate (2,4‐D)

Microbial activities and the versatility gained through adaptation to xenobiotic compounds are the main biological forces to counteract environmental pollution. The current results present a new adaptive mechanism that is mediated through posttranslational modifications. Strains of Delftia acidovorans incapable of growing autochthonously on 2,4‐dichlorophenoxyacetate (2,4‐D) were cultivated in a chemostat on 2,4‐D in the presence of (R)‐2‐(2,4‐dichlorophenoxy)propionate. Long‐term cultivation led to enhanced 2,4‐D degradation, as demonstrated by improved values of the Michaelis–Menten constant K_m for 2,4‐D and the catalytic efficiency k_cat/K_m of the initial degradative key enzyme (R)‐2‐(2,4‐dichlorophenoxy)propionate/α‐ketoglutarate‐dependent dioxygenases (RdpA). Analyses of the rdpA gene did not reveal any mutations, indicating a nongenetic mechanism of adaptation. 2‐DE of enzyme preparations, however, showed a series of RdpA forms varying in their pI. During adaptation increased numbers of RdpA variants were observed. Subsequent immunoassays of the RdpA variants showed a specific reaction with 2,4‐dinitrophenylhydrazine (DNPH), characteristic of carbonylation modifications. Together these results indicate that posttranslational carbonylation modified the substrate specificity of RdpA. A model was implemented explaining the segregation of clones with improved degradative activity within the chemostat. The process described is capable of quickly responding to environmental conditions by reversibly adapting the degradative potential to various phenoxyalkanoate herbicides.     

Asymmetric catalysis of homo‐coupling of 3‐substituted naphthylamine and hetero‐coupling with 3‐substituted naphthol leading to 3,3′‐dimethyl‐2,2′‐diaminobinaphthyl and ‐2‐amino‐2′‐hydroxybinaphthyl

Optically active 3,3′‐dimethyl‐2,2′‐diamino‐1,1′‐binaphthyl (DM‐DABN) and 3,3′‐dimethyl‐2‐amino‐2′‐hydroxybinaphthyl (DM‐NOBIN) derivatives were synthesized by Cu‐(?)‐sparteine complex‐catalyzed enantioselective homo‐ and hetero‐coupling of 2‐naphthylamine, respectively. The difference in enantioselectivity was observed by changing the concentration of oxygen. Chirality, 2010. © 2009 Wiley‐Liss, Inc.     

Stereoselective synthesis of fully protected (2S,4S,6S)‐2‐amino‐6‐hydroxy‐4‐methyl‐8‐oxodecanoic acid (AHMOD)

The stereocontrolled synthesis of fully protected (2S,4S,6S)‐2‐amino‐6‐hydroxy‐4‐methyl‐8‐oxodecanoic acid was accomplished using a glutamate derivative as starting material. The key steps of this stereochemical synthetic pathway involved an Evans asymmetric alkylation, a Sharpless asymmetric epoxidation, and a Grignard reaction. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.     

Synthesis of 3‐Methylidene‐1‐tosyl‐2,3‐dihydroquinolin‐4(1H)‐ones as Potent Cytotoxic Agents

An efficient synthetic strategy to 3‐methylidene‐2,3‐dihydroquinolin‐4(1H)‐ones variously substituted in position 2 has been developed. The title compounds were synthesized in the reaction sequence involving reaction of diethyl methylphosphonate with methyl 2‐(tosylamino)benzoate, condensation of thus formed diethyl 2‐oxo‐2‐(2‐N‐tosylphenyl)ethylphosphonate with various aldehydes followed by successful application of the obtained 3‐(diethoxyphosphoryl)‐1,2‐dihydroquinolin‐4‐ols as Horner–Wadsworth–Emmons reagents for the olefination of formaldehyde. Also, enantioselective approach to the target compounds has been evaluated using 3‐dimenthoxyphosphoryl group as a chiral auxiliary. Single X‐ray crystal analysis of (2S)‐3‐(dimenthoxyphosphoryl)‐2‐phenyl‐1‐tosyldihydroquinolin‐4‐ol revealed the presence of strong resonance‐assisted hydrogen bond (RAHB). The obtained 3‐methylidene‐2,3‐dihydroquinolin‐4(1H)‐ones were then tested for their cytotoxic activity against two leukemia cell lines NALM‐6 and HL‐60 and a breast cancer MCF‐7 cell line. All compounds showed very high cytotoxic activity with the IC₅₀ values mostly below 1 μm in all three cancer cell lines. The selected analogs were also tested on human umbilical vein endothelial cells (HUVEC) and on human mammary gland/breast cells (MCF‐10A) to evaluate their influence on normal cells. Since one of the most serious problems in cancer chemotherapy is the development of drug resistance, the mRNA levels and activity of ABCB1 transporter considered to be the most important factor engaged in drug resistance, were evaluated in MCF‐7 cells treated with two selected analogs. Both compounds were strong ABCB1 transporter inhibitors that could prevent efflux of anticancer drugs from cancer cells.     

Substituent effects on chiral resolutions of derivatized 1‐phenylalkylamines by heptakis(2,3‐di‐O‐methyl‐6‐O‐tert‐butyldimethylsilyl)‐β‐cyclodextrin GC stationary phase

Chiral resolutions of trifluoroacetyl‐derivatized 1‐phenylalkylamines with different type and position of substituent were investigated by capillary gas chromatography by using heptakis(2,3‐di‐O‐methyl‐6‐O‐tert‐butyldimethylsilyl)‐β‐cyclodextrin diluted in OV‐1701 as a chiral stationary phase. The influence of column temperature on retention and enantioselectivity was examined. All enantiomers of meta‐substituted analytes as well as fluoro‐substituted analytes could be resolved. Temperature had a favorable influence on enantioselectivity for small amines with substituents at the ortho‐position. The type of substituent at the stereogenic center of amines also had a crucial effect as the ethyl group led to poor enantioseparation. Among all analytes studied, trifluoroacetyl‐derivatized 1‐(2′‐fluorophenyl)ethylamine exhibited baseline resolution with the shortest analysis time.     

Fluorescence enhancement of europium (III) perchlorate by 1,10‐phenanthroline on the 1‐(naphthalen‐2‐yl)‐2‐(phenylsulthio)ethanone complex and luminescence mechanism

A novel ligand, 1‐(naphthalen‐2‐yl)‐2‐(phenylsulthio)ethanone was synthesized using a new method and its two europium (Eu) (III) complexes were synthesized. The compounds were characterized by elemental analysis, coordination titration analysis, molar conductivity, infrared, thermo gravimetric analyzer‐differential scanning calorimetry (TGA‐DSC), ¹H NMR and UV spectra. The composition was suggested as EuL₅ · (ClO₄)₃ · 2H₂O and EuL₄ · phen(ClO₄)₃ · 2H₂O (L = C₁₀H₇COCH₂SOC₆H₅). The fluorescence spectra showed that the Eu(III) displayed strong characteristic metal‐centered fluorescence in the solid state. The ternary rare earth complex showed stronger fluorescence intensity than the binary rare earth complex in such material. The strongest characteristic fluorescence emission intensity of the ternary system was 1.49 times as strong as that of the binary system. The phosphorescence spectra were also discussed. Copyright © 2014 John Wiley & Sons, Ltd.     

Design,Synthesis and Bioevaluation of Two Series of 3‐[(1‐Benzyl‐1H‐1,2,3‐triazol‐4‐yl)methyl]quinazolin‐4(3H)‐ones and N‐(1‐Benzylpiperidin‐4‐yl)quinazolin‐4‐amines

Two series of 3‐[(1‐benzyl‐1H‐1,2,3‐triazol‐4‐yl)methyl]quinazolin‐4(3H)‐ones and N‐(1‐benzylpiperidin‐4‐yl)quinazolin‐4‐amines were designed initially as potential acetylcholine esterase inhibitors. Biological evaluation demonstrated that N‐(1‐benzylpiperidin‐4‐yl)quinazolin‐4‐amines significantly inhibited AChE activity. Especially, two compounds of them were found to be the most potent with relative AChE inhibition percentages of 87 % in comparison to donepezil. The docking studies with AChE showed similar interactions between donepezil and four derivatives. N‐(1‐Benzylpiperidin‐4‐yl)quinazolin‐4‐amines also exhibited significant DPPH scavenging effects. The two series of compound also exerted moderate to good cytotoxicity against three human cancer cell lines, including SW620 (human colon cancer), PC‐3 (prostate cancer), and NCI?H23 (lung cancer), with 3‐[(1‐benzyl‐1H‐1,2,3‐triazol‐4‐yl)methyl]quinazolin‐4(3H)‐one being the most cytotoxic agent. 3‐[(1‐Benzyl‐1H‐1,2,3‐triazol‐4‐yl)methyl]quinazolin‐4(3H)‐one significantly induced early apoptosis and arrested the SW620 cells at G2/M phase. From this study, two compounds of N‐(1‐benzylpiperidin‐4‐yl)quinazolin‐4‐amines could serve as new leads for further design and AChE inhibitors, while 3‐[(1‐benzyl‐1H‐1,2,3‐triazol‐4‐yl)methyl]quinazolin‐4(3H)‐one could serve as a new lead for the design and development of more potent anticancer agents.     

New chiral stationary phases based on (R)‐1‐naphthylethylamine bound to 2,4,5,6‐tetrachloro‐1,3‐dicyanobenzene

Chiral functionalization of 2,4,5,6‐tetrachloro‐1,3‐dicyanobenzene (1) by regioselective nucleophilic substitution of one or two chlorine atoms by optically pure (R)‐(+)‐1‐naphthylethylamine (NEA), or by a glycine unit as a spacer to (R)‐NEA, enables the preparation of brush‐type chiral selectors (2, 3, 9, 13). By the introduction of the 3‐aminopropyltriethoxysilyl (APTES) group, reactive intermediates 4a/b, 5, 10a/b, and 14a/b are obtained ( a/b indicate a mixture of regioisomers with APTES in 6‐ and 2‐position). Binding of these to silica gel afforded four novel chiral stationary phases (CSPs) 6, 7, 15, and 16. HPLC columns containing CSPs with (R)‐NEA directly linked to polysubstituted aromatic ring (6, 7) are not very effective in resolution of most of the 23 racemic analytes, whereas the columns with distant π‐basic subunits (15, 16) exhibited higher resolving efficacy, in particular towards the isopropyl esters of racemic N‐3,5‐dinitrobenzoyl‐α‐amino acids. Effective resolution of test racemates reveals the importance of the presence of the hydrogen bond donor amido group and the distance between the persubstituted benzene ring in 1 and the π‐basic naphthalene ring of (R)‐NEA. Chirality 11:722–730, 1999. © 1999 Wiley‐Liss, Inc.