Chemistry Central Journal最新文献

Background: The synthesis of new thiazole derivatives is very important because of their diverse biological activities. Also , many drugs containing thiazole ring in their skeletons are available in the market such as Abafungin, Acotiamide, Alagebrium, Amiphenazole, Brecanavir, Carumonam, Cefepime, and Cefmatilen.

Results: Ethyl cyanoacetate reacted with phenylisothiocyanate, chloroacetone, in two different basic mediums to afford the thiazole derivative 6, which reacted with dimethylformamide- dimethyl acetal in the presence of DMF to afford the unexpected thiazole derivative 11. The structures of the thiazoles 6 and 11 were optimized using B3LYP/6-31G(d,p) method. The experimentally and theoretically geometric parameters agreed very well. Also, the natural charges at the different atomic sites were predicted. HOMO and LUMO demands were discussed. The anticancer activity of the prepared compounds was evaluated and showed moderate activity.

Conclusions: Synthesis of novel thiazole derivatives was done. The structure was established using X-ray and spectral analysis. Optimized molecular structures at the B3LYP/6-31G(d,p) level were investigated. Thiazole derivative 11 has more electropositive S-atom than thiazole 6. The HOMO-LUMO energy gap is lower in the former compared to the latter. The synthesized compounds showed moderate anticancer activity.

Background: There is no fluorescence spectroscopic method for the determination of trigonelline and theobromine in green coffee beans. Therefore, the objective of this study was to develop a new fluorescence spectroscopic method to determine the alkaloids simultaneously in the aqueous extract of green coffee beans.

Results: The calibration curves were linear in the range 2-6, 1-6, 1-5 mg/L for caffeine, theobromine and trigonelline, respectively, with R² ≥ 0.9987. The limit of detection and limit of quantification were 2, 6 and 7 µg/L and 40, 20 and 20 µg/L for caffeine, theobromine and trigonelline, respectively. Caffeine and trigonelline exhibited well separated fluorescence excitation spectra and therefore the two alkaloids were selectively quantified in the aqueous extract of green coffee. While theobromine showed overlapping fluorescence excitation spectra with caffeine and hence theobromine could not be determined in the aqueous extract of green coffee beans. The amount of caffeine and trigonelline in the three samples of green coffee beans were found to be 0.95-1.10 and 1.00-1.10% (w/w), respectively. The relative standard deviations (RSD ≤ 4%) of the method for the three compounds of interest were of very good. The accuracy of the developed analytical method was evaluated by spiking standard caffeine and trigonelline to green coffee beans and the average recoveries were 99 ± 2% for both the alkaloids.

Conclusions: A fast, sensitive and reliable fluorescence method for the simultaneous determination of caffeine and trigonelline in the aqueous extract of green coffee beans was developed and validated. The developed method reflected an effective performance to the direct determination of the two alkaloids in the aqueous extract of green coffee beans.

A fast method for the identification and stability evaluation of the aggregation pheromone rhynchophorol, which is the main substance used for chemical communication by the beetle Rhynchophorus palmarum L., was validated. In addition, the technique was applied to the evaluation of two inorganic matrices, with the objective of using them as controlled-release devices. The analytical method showed good linearity (R² = 0.9978), precision (CV% < 1.79), recovery (84-105%) and limits of detection (0.2 mg mL^-1) and quantification (0.3 mg mL^-1); in compliance with the validation legislation established by ANVISA. In the interaction study, the inorganic matrices zeolite L and Na-magadiite showed high rates of pheromone recovery without promoting its degradation for a period of 180 days, which is not reported in the literature for other matrices. The structures of the zeolite L/rhynchophorol and Na-magadiite/rhynchophorol composites showed slower release kinetics during the storage period when compared with pure pheromone, which is desirable since it extends the period of rhynchophorol release and decreases the negative effects caused by the environmental parameters.

Background: In order to develop new larvicidal agents derived from phytochemicals, the larvicidal activity of fifty molecules that are constituent of essential oils was evaluated against Culex quinquefasciatus Say. Terpenes, terpenoids and phenylpropanoids molecules were included in the in vitro evaluation, and QSAR models using genetic algorithms were built to identify molecular and structural properties of biological interest. Further, to obtain structural details on the possible mechanism of action, selected compounds were submitted to docking studies on sterol carrier protein-2 (SCP-2) as possible target.

Results: Results showed high larvicidal activity of carvacrol and thymol on the third and fourth larval stage with a median lethal concentration (LC₅₀) of 5.5 and 11.1 µg/mL respectively. Myrcene and carvacrol were highly toxic for pupae, with LC₅₀ values of 31.8 and 53.2 µg/mL. Structure-activity models showed that the structural property π-bonds is the largest contributor of larvicidal activity while ketone groups should be avoided. Similarly, property-activity models attributed to the molecular descriptor LogP the most contribution to larvicidal activity, followed by the absolute total charge (Qtot) and molar refractivity (AMR). The models were statistically significant; thus the information contributes to the design of new larvicidal agents. Docking studies show that all molecules tested have the ability to interact with the SCP-2 protein, wherein α-humulene and β-caryophyllene were the compounds with higher binding energy.

Conclusions: The description of the molecular properties and the structural characteristics responsible for larvicidal activity of the tested compounds were used for the development of mathematical models of structure-activity relationship. The identification of molecular and structural descriptors, as well as studies of molecular docking on the SCP-2 protein, provide insight on the mechanism of action of the active molecules, and the information can be used for the design of new structures for synthesis as potential new larvicidal agents.

Background: Psidium guineense, known as Araçá, is a Brazilian botanical resource with commercial application perspectives, based on the functional elements of its fruits and due to the use of its leaves as an anti-inflammatory and antibacterial agent. The essential oils of leaves of twelve specimens of Araçá were analyzed by GC and GC-MS to identify their volatile constituents and associate them with the biological activities reputed to the plant.

Results: In a total of 157 identified compounds, limonene, α-pinene, β-caryophyllene, epi-β-bisabolol, caryophyllene oxide, β-bisabolene, α-copaene, myrcene, muurola-4,10(14)-dien-1-β-ol, β-bisabolol, and ar-curcumene were the primary components in descending order up to 5%. Hierarchical Cluster Analysis (HCA) and Principal Component Analysis (PCA) displayed three different groups with the following chemical types: limonene/α-pinene, β-bisabolene/epi-β-bisabolol, and β-caryophyllene/caryophyllene oxide. With the previous description of another chemical type rich in spathulenol, it is now understood that at least four different chemotypes for P. guineense should occur.

Conclusions: In addition to the use of the Araçá fruits, which are rich in minerals and functional elements, it should be borne in mind that the knowledge of the chemical composition of the essential oils of leaves of their different chemical types may contribute to the selection of varieties with more significant biological activity.

A novel series of substituted 2-thiohydantoin incorporated with benzoimidazole, pyrazole, triazole and/or benzoxazole moieties has been synthesized using (E)-3-[1-(4-bromophenyl)ethylideneamino]-2-thioxoimidazolidin-4-one 1 as the key starting material. The key material 1 also, reacted with an acetic anhydride, aromatic aldehydes, secondary amines, formaldehyde and triethyl orthoformate to give the corresponding acetyl, chalcone, Mannich bases and ethoxymethylene derivatives, respectively. The structures of the novel compounds were confirmed by spectral data and elemental analysis. The cytotoxic activity of all synthesized compounds was assessed in vitro against human hepatocellular cancer cell line (HePG-2) and breast carcinoma cell line (MCF-7). The bioassay results revealed that compound 14 has the best activity against HePG-2 cell line (IC₅₀ = 2.33 μg/mL), while compound 5 has the best activity against MCF-7 cell line (IC₅₀ = 3.98 μg/mL).

Background and objective: A series of thiazolopyrimidine derivatives have been synthesized via multicomponent reaction and tested for biological activities. This research aims to develop a new synthetic method of poly fused pyrimidines under microwave irradiation. 6-Amino-4-aryl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitriles reacted with bromomalono-nitrile to give 3,7-diamino-5-aryl-5H-thiazolo[3,2-a]pyrimidine-2,6-dicarbonitrile more willingly than the isomeric 7H-thiazolo[3,2-a]pyrimidines. Thiazolopyrimidine derivatives reacted with carbon disulphide to produce 11-aryl-11H-1,2,3,4,7,8,9,10-octahydropyrimido[4″,5″:4',5']thiazolo[3',2'-a]pyrimido[4,5-d]pyrimidine-2,4,8,10-tetrathione. The above mentioned reactions were established by using both conventional methods and microwave-assisted irradiation.

Conclusion: This work provides a new method for preparing poly fused pyrimidines. The microwave-assisted technique is preferable due to the yield enhancements attained, time saving, and environmental safety reactions. The newly prepared compounds were verified for their antimicrobial activities. Also, the absorption and emission of some of the prepared compounds were studied.

Thiophene derivatives have shown versatile pharmacological activities. The Suzuki reaction proved a convenient method for C-C bond formations in organic molecules. In the present research work novel derivatives of 2,5-dibromo-3-methylthiophene (3a-k and 3l-p) has been synthesized, via Suzuki coupling reaction in low to moderate yields. A wide range of functional groups were well tolerated in reaction. Density functional theory investigations on all synthesized derivatives (3a-3p) were performed in order to explore the structural properties. The pharmaceutical potential of synthesized compounds was investigated through various bioassays (antioxidant, antibacterial, antiurease activities). The compounds 3l, 3g, 3j, showed excellent antioxidant activity (86.0, 82.0, 81.3%), respectively by scavenging DPPH. Synthesized compounds showed promising antibacterial activity against tested strains. 3b, 3k, 3a, 3d and 3j showed potential antiurease activity with 67.7, 64.2, 58.8, 54.7 and 52.1% inhibition at 50 µg/ml. Results indicated that synthesized molecules could be a potential source of pharmaceutical agents.

Traditional Chinese medicine (TCM), as a unique form of natural medicine, has been used in Chinese traditional therapeutic systems over two thousand years. Active components in Chinese herbal medicine are the material basis for the prevention and treatment of diseases. Research on drug-protein binding is one of the important contents in the study of early stage clinical pharmacokinetics of drugs. Plasma protein binding study has far-reaching influence on the pharmacokinetics and pharmacodynamics of drugs and helps to understand the basic rule of drug effects. It is important to study the binding characteristics of the active components in Chinese herbal medicine with plasma proteins for the medical science and modernization of TCM. This review summarizes the common analytical methods which are used to study the active herbal components-protein binding and gives the examples to illustrate their application. Rules and influence factors of the binding between different types of active herbal components and plasma proteins are summarized in the end. Finally, a suggestion on choosing the suitable technique for different types of active herbal components is provided, and the prospect of the drug-protein binding used in the area of TCM research is also discussed.

Purpose: To develop and validate a bio-analytical HPLC-MS/MS method for the determination of conivaptan (CVA) an arginine-vasopressin receptor blocker in human plasma and in rat liver microsomes (RLMs).

Methods: Analytes were separated on a reversed phase C18 column (50 mm × 2.1 mm, 1.8 μm). The mobile phase was a mixture of acetonitrile and 10 mM ammonium formate (40:60 v/v, pH 4.0) and was pumped isocratically for 4 min at a flow rate of 0.2 ml/min. Multiple reaction monitoring in positive ionization mode was used for the assay.

Results: The method yielded a linear calibration plot (r ² = 0.9977 and 0.9998) over 5-500 ng/ml with a limit of detection at 1.52 and 0.88 ng/ml for human plasma and RLMs, respectively. The reproducibility of detection of CVA in human plasma and RLMs was found to be in an acceptable range.

Conclusion: The method developed in this study is applicable for accurately quantifying CVA in human plasma and rat liver microsomal samples. The optimized procedure was applied to study of metabolic stability of CVA. Conivaptan concentration rapidly decreased in the first 2 min of RLMs incubation and the conversion reached a plateau for the remainder of the incubation period. The in vitro half-life (t_1/2) was estimated at 11.51 min and the intrinsic clearance (CL_in) was 13.8 ± 0.48 ml/min/kg.