Synthesis of 2-(α-Hydroxyalkyl)-2-Oxazoline under Microwave Irradiation in Bluk

Four 2-(α-hydroxyalkyl)-2-oxazolines and a 2-(α-hydroxy-α,α-diphenyl)-2-benzooxazole were synthesized from β-amimoalcohols and α-hydroxy carboxylic acids under microwave irradiation in the absence of a solvent.     

Synthesis of 4b,5,10a,11-tetrahydroindeno[1,2-b]quinolin-10-ones from Baylis-Hillman adducts

We developed an efficient synthetic method for indenoquinoline skeletons from Baylis-Hillman adducts. 4b,5,10a,11-Tetrahydroindeno[1,2-b]quinolin-10-ones and 7H-indeno[2,1-c]quinolines were prepared from Baylis-Hillman adducts in polyphosphoric acid.     

Nucleation of β-hairpin structure in a pyrrole amino acid containing peptide

Synthesis and conformational studies of two short peptides containing pyrrole amino acids (1, Paa), Boc-Paa-Paa-d-Pro-Gly-Xaa-Paa-Paa-OMe (2: Xaa=Ala; 3: Xaa=Val), were carried out in which it was established that replacement of Ala in 2 with a Val residue helps peptide 3 to adopt a well-defined β-hairpin conformation in a nonpolar solvent, like CDCl₃.     

Disposable multichannel immunosensors for 2,4-dichlorophenoxyacetic acid using acetylcholinesterase as an enzyme label

An improved version of the disposable multichannel immunochemical biosensor for the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) based on a screen-printed amperometric transducer and monoclonal antibodies (MAb) against 2,4-D is reported. Entrapment within a thin Nafion film was used for the direct immobilization of MAb at the electrode surface. The amount of the tracer (2,4-D conjugated to acetylcholinesterase) bound in a competitive immunochemical reaction was determined amperometrically using acetylthiocholine iodide as substrate. The measuring procedure (times of incubation with tracer and substrate, pH, tracer concentration) was optimized. The sensor was able to detect less than 0.01 μg/L of free 2,4-D in water. One analysis (8 samples) was completed in 30 min (20 min for immunochemical reaction, 5 min incubation with substrate, 5 min measurement). The performance of the immunosensor (two configurations) was evaluated on real samples (tap water) with added 2,4-D. The determined amounts (mean values 0.097 to 0.105 and 0.89 to 1.13) corresponded well with the added contents of 2,4-D (0.100 and 1.00 μg/L, respectively).     

Capillary Zone Electrophoresis of some organic acids in milk whey

This paper describes a method for analysing some acids of milk whey by Capillary Zone Electrophoresis. After eliminating the whey proteins by ultrafiltration, the whey underwent electrophoretic separation in the presence of anodic electroosmotic flow. The following analytes were detected: citric, orotic, uric, and hippuric acids. A procedure is described for sample preparation and the operating conditions for electrophoretic capillary separation established. Finally, orotic acid is quantitatively determined.     

Conformation of poly(L-glutamic acid) in aqueous solutions of linear amphiphiles with a cationic group at both ends

The conformations of poly(l-glutamic acid) [P(Glu)] in solutions of the bipolar amphiphile 1,20-icosanediylbis(alkylammonium chloride) [C20(RA)₂], where RA includes trimethylammonium (TMA), dimethylammonium (DMA), or methylammonium (MA), were investigated with measurements of the circular dichroism spectra at 10–35 °C. All C20(RA)₂ induced an α-helix of P(Glu) in the aqueous solutions. The residue molar ellipticity at 222 nm showed a similar dependence on the amphiphile concentration (C _s) below 0.5 of the ratio of 2C _s to the residue concentration (C _p) of P(Glu), but it separated into three directions at 2C _s/C _p>0.5. C20(MA)₂ induced an α-helix of P(Glu) at 2C _s/C _p<0.5 followed by a helix aggregate at 2C _s/C _p>0.5. C20(DMA)₂ and C20(TMA)₂ also induced an α-helix, but a helix aggregate. C20(TMA)₂ indicated a strong temperature dependence and did not induce a complete α-helix at 35 °C. Received: 20 June 2001 Accepted: 6 September 2001     

Oxonitrogenated Derivatives of Eremophilans and Eudesmans: Antiproliferative and Anti-Trypanosoma cruzi Activity

Cancer is one of the most important causes of death worldwide. Solid tumors represent the vast majority of cancers (>90%), and the chemotherapeutic agents used for their treatment are still characterized by variable efficacy and toxicity. Sesquiterpenes are a group of natural compounds that have shown a wide range of biological activities, including cytotoxic and antiparasitic activity, among others. The antiproliferative activity of natural sesquiterpenes, tessaric acid, ilicic acid, and ilicic alcohol and their semisynthetic derivatives against HeLa, T-47D, WiDr, A549, HBL-100, and SW1573 cell lines were evaluated. The effect of the compounds on Trypanosoma cruzi epimastigotes was also assessed. The selectivity index was calculated using murine splenocytes. Derivatives 13 and 15 were the most antiproliferative compounds, with GI₅₀ values ranging between 5.3 (±0.32) and 14 (±0.90) μM, in all cell lines tested. The presence of 1,2,3-triazole groups in derivatives 15–19 led to improvements in activity compared to those corresponding to the starting natural product (3), with GI₅₀ values ranging between 12 (±1.5) and 17 (±1.1) μM and 16 being the most active compound. In relation to the anti-T. cruzi activity, derivatives 7 and 16 obtained from tessaric acid and ilicic acid were among the most active and selective compounds with IC₅₀ values of 9.3 and 8.8 µM (SI = 8.0 and 9.4), respectively.     

A Comprehensive Review of Rosmarinic Acid: From Phytochemistry to Pharmacology and Its New Insight

Polyphenolic acids are the widely occurring natural products in almost each herbal plant, among which rosmarinic acid (RA, C₁₈H₁₆O₈) is well-known, and is present in over 160 species belonging to many families, especially the Lamiaceae. Aside from this herbal ingredient, dozens of its natural derivatives have also been isolated and characterized from many natural plants. In recent years, with the increasing focus on the natural products as alternative treatments, a large number of pharmacological studies have been carried out to demonstrate the various biological activities of RA such as anti-inflammation, anti-oxidation, anti-diabetes, anti-virus, anti-tumor, neuroprotection, hepatoprotection, etc. In addition, investigations concerning its biosynthesis, extraction, analysis, clinical applications, and pharmacokinetics have also been performed. Although many achievements have been made in various research aspects, there still exist some problems or issues to be answered, especially its toxicity and bioavailability. Thus, we hope that in the case of natural products, the present review can not only provide a comprehensive understanding on RA covering its miscellaneous research fields, but also highlight some of the present issues and future perspectives worth investigating later, in order to help us utilize this polyphenolic acid more efficiently, widely, and safely.     

Insecticidal Activity of Organic Extracts of Solidago graminifolia and Its Main Metabolites (Quercetin and Chlorogenic Acid) against Spodoptera frugiperda: An In Vitro and In Silico Approach

Spodoptera frugiperda (S. frugiperda) remains a global primary pest of maize. Therefore, new options to combat this pest are necessary. In this study, the insecticidal activity of three crude foliar extracts (ethanol, dichloromethane, and hexane) and their main secondary metabolites (quercetin and chlorogenic acid) of the species Solidago graminifolia (S. graminifolia) by ingestion bioassays against S. frugiperda larvae was analyzed. Additionally, the extracts were phytochemically elucidated by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) analysis. Finally, an in silico study of the potential interaction of quercetin on S. frugiperda acetylcholinesterase was performed. Organic extracts were obtained in the range from 5 to 33%. The ethanolic extract caused higher mortality (81%) with a half-maximal lethal concentration (LC₅₀) of 0.496 mg/mL. Flavonoid secondary metabolites such as hyperoside, quercetin, isoquercetin, kaempferol, and avicularin and some phenolic acids such as chlorogenic acid, solidagoic acid, gallic acid, hexoside, and rosmarinic acid were identified. In particular, quercetin had an LC₅₀ of 0.157 mg/mL, and chlorogenic acid did not have insecticidal activity but showed an antagonistic effect on quercetin. The molecular docking analysis of quercetin on the active site of S. frugiperda acetylcholinesterase showed a −5.4 kcal/mol binding energy value, lower than acetylcholine and chlorpyrifos (−4.45 and −4.46 kcal/mol, respectively). Additionally, the interactions profile showed that quercetin had π–π interactions with amino acids W198, Y235, and H553 on the active site.     

The Effects of Charged Amino Acid Side-Chain Length on Diagonal Cross-Strand Interactions between Carboxylate- and Ammonium-Containing Residues in a β-Hairpin

The β-sheet is one of the common protein secondary structures, and the aberrant aggregation of β-sheets is implicated in various neurodegenerative diseases. Cross-strand interactions are an important determinant of β-sheet stability. Accordingly, both diagonal and lateral cross-strand interactions have been studied. Surprisingly, diagonal cross-strand ion-pairing interactions have yet to be investigated. Herein, we present a systematic study on the effects of charged amino acid side-chain length on a diagonal ion-pairing interaction between carboxylate- and ammonium-containing residues in a β-hairpin. To this end, 2D-NMR was used to investigate the conformation of the peptides. The fraction folded population and the folding free energy were derived from the chemical shift data. The fraction folded population for these peptides with potential diagonal ion pairs was mostly lower compared to the corresponding peptide with a potential lateral ion pair. The diagonal ion-pairing interaction energy was derived using double mutant cycle analysis. The Asp2-Dab9 (Asp: one methylene; Dab: two methylenes) interaction was the most stabilizing (−0.79 ± 0.14 kcal/mol), most likely representing an optimal balance between the entropic penalty to enable the ion-pairing interaction and the number of side-chain conformations that can accommodate the interaction. These results should be useful for designing β-sheet containing molecular entities for various applications.