Localization of 9- and 13-oxo-octadecadienoic acids in tomato fruit

We previously reported that the two peroxisome proliferator-activated receptor-α agonists, 9- and 13-oxo-octadecadienoic acids (oxo-ODAs), were found in the tomato fruit. However, their localization remains unknown. Herein, we showed that oxo-ODAs localize primarily in the fruit peel and their amount increases after the homogenization of the tomato fruit.     

Further Thymol Derivatives from Ageratina cylindrica

From the leaves of Ageratina cylindrica, in addition to the described [(2S)‐2‐{4‐formyl‐5‐hydroxy‐2‐[(2‐methylpropanoyl)oxy]phenyl}oxiran‐2‐yl]methyl benzoate (cylindrinol A, 8 ), seven new thymol derivatives were isolated and named cylindrinols B – H ( 1 – 7 ). The structures of these compounds were established as (2‐{4‐(hydroxymethyl)‐2‐[(2‐methylpropanoyl)oxy]phenyl}oxiran‐2‐yl)methyl benzoate ( 1 ), (2‐{4‐formyl‐2‐[(2‐methylpropanoyl)oxy]phenyl}oxiran‐2‐yl)methyl benzoate ( 2 ), (2‐{4‐[(acetyloxy)methyl]‐2‐[(2‐methylpropanoyl)oxy]phenyl}oxiran‐2‐yl)methyl benzoate ( 3 ), [2‐(2‐[(2‐methylpropanoyl)oxy]‐4‐{[(2‐methylpropanoyl)oxy]methyl}phenyl)oxiran‐2‐yl]methyl benzoate ( 4 ), [2‐(5‐hydroxy‐2‐[(2‐methylpropanoyl)oxy]‐4‐{[(2‐methylpropanoyl)oxy]methyl}phenyl)oxiran‐2‐yl]methyl benzoate ( 5 ), 2‐{4‐(hydroxymethyl)‐2‐[(2‐methylpropanoyl)oxy]phenyl}prop‐2‐en‐1‐yl benzoate ( 6 ), and 2‐hydroxy‐2‐[2‐hydroxy‐4‐(hydroxymethyl)‐phenyl]‐3‐[(2‐methylpropanoyl)oxy]propyl benzoate ( 7 ), by spectroscopic means. Compounds 1 showed moderate antiprotozoal activity on both protozoa. Compounds 4 and 5 showed selectivity on Giardia lamblia trophozoites. All isolated compounds were less active than two antiprotozoal drugs, metronidazole and emetine, used as positive controls. Compound 5 exhibited a high inhibitory effect on hyperpropulsive movement of the small intestine in rats; its effect was best than loperamide, antidiarrheal drug used as a positive control.     

Graphene quantum dots as additives in capillary electrophoresis for separation cinnamic acid and its derivatives

A facile capillary electrophoresis (CE) method for the separation of cinnamic acid and its derivatives (3,4-dimethoxycinnamic acid, 4-methoxycinnamic acid, isoferulic acid, sinapic acid, cinnamic acid, ferulic acid, and trans-4-hydroxycinnamic acid) using graphene quantum dots (GQDs) as additives with direct ultraviolet (UV) detection is reported. GQDs were synthesized by chemical oxidization and further purified by a macroporous resin column to remove salts (Na₂SO₄ and NaNO₃) and other impurities. Transmission electron microscopy (TEM) indicated that GQDs have a relatively uniform particle size (2.3 nm). Taking into account the structural features of GQDs, cinnamic acid and its derivatives were adopted as model compounds to investigate whether GQDs can be used to improve CE separations. The separation performance of GQDs used as additives in CE was studied through variations of pH, concentration of the background electrolyte (BGE), and contents of GQDs. The results indicated that excellent separation can be achieved in less than 18 min, which is mainly attributed to the interaction between the analytes and GQDs, especially isoferulic acid, sinapic acid, and cinnamic acid.     

Dihydropyrimidine based hydrazine dihydrochloride derivatives as potent urease inhibitors

Four series of heterocyclic compounds 4-dihydropyrimidine-2-thiones 7–12 (series A), N,S-dimethyl-dihydropyrimidines 13–18 (series B), hydrazine derivatives of dihydropyrimidine 19–24 (series C), and tetrazolo dihydropyrimidine derivatives 25–30 (series D), were synthesized and evaluated for in vitro urease inhibitory activity. The series B–D were first time examined for urease inhibition. Series A and C were found to be significantly active with IC₅₀ values between 34.7–42.9 and 15.0–26.0 μM, respectively. The structure–activity relationship showed that the free S atom and hydrazine moiety are the key pharmacophores against urease enzyme. The kinetic studies of the active series A (7–12) and C (19–24) were carried out to determine their modes of inhibition and dissociation constants K_i. Compounds of series A (7–12) and series C (19–24) showed a mixed-type of inhibition with K_i values ranging between 15.76–25.66 and 14.63–29.42 μM, respectively. The molecular docking results showed that all the active compounds of both series have significant binding interactions with the active sites specially Ni-ion of the urease enzyme. Cytotoxicity of all series A–D was also evaluated against mammalian mouse fibroblast 3T3 cell lines, and no toxicity was observed in cellular model.     

Molecular docking studies and biological evaluation of 1,3,4-thiadiazole derivatives bearing Schiff base moieties as tyrosinase inhibitors

1,3,4-Thiadiazole derivatives bearing Schiff base moieties were designed, synthesized, and their tyrosinase inhibitory activities were evaluated. Some compounds displayed potent tyrosinase inhibitory activities, especially, 4-(((5-mercapto-1,3,4-thiadiazol-2-yl)-imino)methyl)-2-methoxy-phenol (14) exhibited superior inhibitory effect to the other compounds with an IC₅₀ value of 0.036 μM. The structure–activity relationships (SARs) were preliminarily discussed and docking studies showed compound 14 had strong binding affinity to mushroom tyrosinase. Hydroxy might be the active groups. The inhibition kinetics study revealed that compounds (13 and 14) inhibited tyrosinase by acting as uncompetitive inhibitors. The LD₅₀ value of the compound 14 was 5000 mg/kg.     

Neuroprotective effects of (E)-3,4-diacetoxystyryl sulfone and sulfoxide derivatives in vitro models of Parkinson's disease

(E)-3,4-dihydroxystyryl aralkyl sulfones and sulfoxides have been reported as novel multifunctional neuroprotective agents in previous studies, which as phenolic compounds display antioxidative and antineuroinflammatory properties. To further enhance the neuroprotective effects and study structure-activity relationship of the derivatives, we synthesized their acetylated derivatives, (E)-3,4-diacetoxystyryl sulfones and sulfoxides, and examined their neuroprotective effects in vitro models of Parkinson’s disease. The results indicate that (E)-3,4-diacetoxystyryl sulfones and sulfoxides can significantly inhibit kinds of neuron cell injury induced by toxicities, including 6-OHDA, NO, and H₂O₂. More important, they show higher antineuroinflammatory properties and similar antioxidative properties to corresponding un-acetylated compounds. Thus, we suggest that (E)-3,4-diacetoxystyryl sulfones and sulfoxides may have potential for the treatment of neurodegenerative disorders, especially Parkinson’s disease.     

Design,synthesis and biological evaluation of 4-benzoyl-1-dichlorobenzoylthiosemicarbazides as potent Gram-positive antibacterial agents

Twelve 4-benzoyl-1-dichlorobenzoylthiosemicarbazides have been tested as potential antibacterials. All the compounds had MICs between 0.49 and 15.63?µg/ml toward Micrococcus luteus, Bacillus cereus, Bacillus subtilis and Staphylococcus epidermidis indicating, in most cases, equipotent or even more effective action than cefuroxime. In order to clarify if the observed antibacterial effects are universal, further research were undertaken to test inhibitory potency of two most potent compounds 3 and 11 on clinical isolates of Staphylococcus aureus. Compound 11 inhibited the growth of methicillin-sensitive S. aureus (MSSA) at MICs of 1.95–7.81?µg/ml, methicillin-resistant S. aureus (MRSA) at MICs of 0.49–1.95?µg/ml and MDR–MRSA at MIC of 0.98 and 3.90?µg/ml, respectively. Finally, inhibitory efficacy of 3 and 11 on planktonic cells and biofilms formation in clinical isolates of S. aureus and Haemophilus parainfluenzae was tested. The majority of cells in biofilm populations of MSSA and MRSA were eradicated at low level of 3, with MBICs in the range of 7.82–15.63?µg/ml.     

Synthesis and carbonic anhydrase inhibitory properties of amino acid – coumarin/quinolinone conjugates incorporating glycine,alanine and phenylalanine moieties

N-Protected amino acids (Gly, Ala and Phe) were reacted with amino substituted coumarin and quinolinone derivatives, leading to the corresponding N-protected amino acid–coumarin/quinolinone conjugates. The carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activity of the new compounds was assessed against various human (h) isoforms, such as hCA I, hCA II, hCA IV and hCA XII. The quinolinone conjugates were inactive as enzyme inhibitors, whereas the coumarins were ineffective hCA I/II inhibitors (K_Is?>?50?μM) but were submicromolar hCA IV and XII inhibitors, with inhibition constants ranging between 92?nM and 1.19?μM for hCA IV, and between 0.11 and 0.79?μM for hCA XII. These coumarin derivatives, as many others reported earlier, thus show an interesting selective inhibitory profile for the membrane-bound over the cytosolic CA isoforms.     

Absolute Configuration Assignment of a Paraconic Acid Derivative via Vibrational Circular Dichroism Spectroscopy and Density Functional Theory Calculation

Density functional theory calculation of the vibrational circular dichroism spectrum was used to assign the absolute configuration of an all‐carbon quaternary β‐stereocenter of a γ‐butyrolactone recently synthesized through an asymmetric organocatalytic tandem aldol/lactonization sequence. Comparison with the experimental spectrum is satisfactory, on account of the fact that spectroscopic features are weak due to the presence of multiple conformers. As a result, the (R) absolute configuration was assigned to the (+) optical isomer. Chirality 28:110–115, 2016. © 2015 Wiley Periodicals, Inc.     

Development of acridine derivatives as selective Mycobacterium tuberculosis DNA gyrase inhibitors

In this study we have designed p-phenylene diamine linked acridine derivative from our earlier reported quinoline–aminopiperidine hybrid MTB DNA gyrase inhibitors with aiming more potency and less cardiotoxicity. We synthesized thirty six compounds using four step synthesis from 2-chloro benzoic acid. Among them compound 4-chloro-N-(4-((2-methylacridin-9-yl)amino)phenyl)benzenesulphonamide (6) was found to be more potent with MTB DNA gyrase super coiling IC₅₀ of 5.21 ± 0.51 μM; MTB MIC of 6.59 μM and no zHERG cardiotoxicity at 30 μM and 11.78% inhibition at 50 μM against mouse macrophage cell line RAW 264.7.