Chemistry Central Journal最新文献

Background: The study describes the synthesis, characterization, in vitro antimicrobial and anticancer evaluation of a series of 2-(1-benzoyl-1H-benzo[d]imidazol-2-ylthio)-N-substituted acetamide derivatives. The synthesized derivatives were also assessed for in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv. The compounds found active in in vitro study were assessed for their in vivo antitubercular activity in mice models and for their inhibitory action on vital mycobacterial enzymes viz, isocitrate lyase, pantothenate synthetase and chorismate mutase.

Results: Compounds 8, 9 and 11 emerged out as excellent antimicrobial agents in antimicrobial assays when compared to standard antibacterial and antifungal drugs. The results of anticancer activity displayed that majority of the derivatives were less cytotoxic than standard drugs (tamoxifen and 5-fluorouracil) towards MCF7 and HCT116 cell lines. However, compound 2 (IC₅₀ = 0.0047 µM/ml) and compound 10 (IC₅₀ = 0.0058 µM/ml) showed highest cytotoxicity against MCF7 and HCT116 cell lines, respectively. The results of in vivo antitubercular activity revealed that a dose of 1.34 mg/kg was found to be safe for the synthesized compounds. The toxic dose of the compounds was 5.67 mg/kg while lethal dose varied from 1.81 to 3.17 mg/kg body weight of the mice. Compound 18 inhibited all the three mycobacterial enzymes to the highest level in comparison to the other synthesized derivatives but showed lesser inhibition as compared to streptomycin sulphate.

Conclusions: A further research on most active synthesized compounds as lead molecules may result in discovery of novel anticancer and antitubercular agents.

Background: Described a series of main target compounds pyrimido[5,4-e][1,2,4]triazines is obtained via condensation of 6-hydrazinyluracil with different aromatic aldehydes to give the hydrazones followed by nitrosation with HNO₂ then intramolecular cyclization. On the other hand, pyrazolopyrimidines can be obtained by the reaction of hydrazones with dimethylformamide-dimethylacetal (DMF-DMA), DMF-DMA in the presence of DMF or by refluxing the hydrazinyluracil with DMF-DMA in the presence of DMF directly. The newly synthesized compounds are evaluated in vitro for their anticancer activity against human lung carcinoma (A549).

Results: A newly substituted compounds of benzaldehyde-pyrimidin-4-yl)hydrazones (5a-f), pyrimido[5,4-e][1,2,4]triazines 6a-e, arylethylidenehydrazinylpyrimidine 7a,b and pyrazolopyrimidines 9,11 are screened for cytotoxic activity against human lung carcinoma (A549) cell line. They exhibited a good yield. Compound 6b shows the highest effect with IC₅₀ value 3.6 μM, followed by compounds 9, 5a, 8, 5e, 6e, 5b, 5f, 7a, 5c, 6c, 7b, 6a, 11, 5d and 6d.

Conclusion: A simple and efficient route is used for the synthesis of pyrimido[5,4-e][1,2,4]triazines and pyrazolopyrimidines. The synthesized compounds are screened for antitumor activity.

Background: Doxorubicin hydrochloride (DOX·HCl), an anthracycline glycoside antibiotic, exhibits low oral bioavailability due to active efflux from intestinal P-glycoprotein receptors. The oral administration of DOX remains a challenge hence; no oral formulation for DOX is marketed, till date.

Aim of the study: To improve the oral bioavailability of DOX through, preparation of a nanoformulation i.e. PEGylated-doxorubicin(DOX)-loaded-poly-lactic-co-glycolic acid (PLGA)-Nanoparticles (NPs) and to develop and validate an ultra-high performance liquid chromatography electrospray ionization-synapt mass spectrometric bioanalytical method (UHPLC/ESI-QTOF-MS/MS) for plasma (Wistar rats) DOX quantification.

Materials and methods: For chromatography, Waters ACQUITY UPLC™ along with a BEH C-18 column (2.1 mm × 100 mm; 1.7 μm), mobile phase conditions (acetonitrile: 0.1% formic acid::1:1 v/v) and flow rate (0.20 ml/min) was used. For analyte recovery from rat plasma, a liquid-liquid extraction method (LLE), using Acetonitrile: 5 mM ammonium acetate in a ratio of 6:4 v/v at pH 3.5, was used.

Results: Nanoformulation with a particle size (183.10 ± 7.41 nm), zeta potential (- 13.10 ± 1.04 mV), drug content (42.69 ± 1.97 µg/mg) and a spherical shape and smooth surface was developed. An elution time of 1.61 and 1.75 min along with a transition at m/z 544.42/397.27 and 528.46/321.41 were observed for DOX and internal standard (IS) Daunorubicin, respectively. In addition, a linear dynamic range with r² ≥ 0.9985 over a concentration range of 1.00-2500.0 ng/ml was observed for different processes and parameters used in the study. Similarly a marked improvement i.e. 6.8 fold was observed, in PEGylated-DOX-PLGA-NPs as compared to DOX-S, in pharmacokinetics studies.

Conclusion: The promising approach of PEGylated-DOX-PLGA-NPs may provide an alternate to intravenous therapy for better patient care.

Background: The extracts from the leaves of Otostegia integrifolia have been reported to show phytochemical analysis, total flavonoid content, antioxidant and antibacterial activities.

Results: Our results revealed that the total flavonoid content of methanol and ethyl acetate extracts is 416.5 + 0.288 and 248.9 + 0.872 mgAAE/100 g respectively. The two extracts also showed good antioxidant activity as well as weak to moderate antibacterial activity against some bacteria.

Conclusions: The leaf extracts from O. integrifolia showed good total flavonoid content, DPPH radical scavenging activity and antibacterial activity. In addition to this, the extracts also showed the presence of some important compounds by phytochemical analysis.

An efficient one pot method for the synthesis of α-alkoxymethylphosphonium iodides is developed by using PPh₃/I₂ combination at room temperature. Reaction conditions are found general to synthesize wide range of structurally variant alkoxymethylphosphonium iodides in high yield (70-91%). These new functionalized phosphonium salts are further used in stereoselective synthesis of vinyl ethers as well as in carbon homologation of aldehydes.

Masitinib (MST) is an orally administered drug that targets mast cells and macrophages, important cells for immunity, by inhibiting a limited number of tyrosine kinases. It is currently registered in Europe and USA for the treatment of mast cell tumors in dogs. AB Science announced that the European Medicines Agency has accepted a conditional marketing authorization application for MST to treat amyotrophic lateral sclerosis. In our work, we focused on studying in vivo metabolism of MST in Sprague-Dawley rats. Single oral dose of MST (33 mg kg^-1) was given to Sprague-Dawley rats (kept in metabolic cages) using oral gavage. Urine was collected and filtered at 0, 6, 12, 18, 24, 48, 72 and 96 h from MST dosing. An equal amount of ACN was added to urine samples. Both organic and aqueous layers were injected into liquid chromatography-tandem mass spectrometry (LC-MS/MS) to detect in vivo phase I and phase II MST metabolites. The current work reports the identification and characterization of twenty in vivo phase I and four in vivo phase II metabolites of MST by LC-MS/MS. Phase I metabolic pathways were reduction, demethylation, hydroxylation, oxidative deamination, oxidation and N-oxide formation. Phase II metabolic pathways were the direct conjugation of MST, N-demethyl metabolites and oxidative metabolites with glucuronic acid. Part of MST dose was excreted unchanged in urine. The literature review showed no previous articles have been made on in vivo metabolism of MST or detailed structural identification of the formed in vivo phase I and phase II metabolites.

Dioscorea nipponica Makino is a perennial twining herbs belonging to the family Dioscoreaceae, which is mainly distributed in the northeastern, northern, eastern and central regions of China. Traditionally, the rhizome of this herb has been commonly used by Miao and Meng ethnic groups of China to treat rheumatoid arthritis, pain in the legs and lumbar area, Kashin Beck disease, bruises, sprains, chronic bronchitis, cough and asthma. Modern pharmacological studies have discovered that this herb possesses anti-tumor, anti-inflammatory, anti-diuretic, analgesic, anti-tussive, panting-calming and phlegm-dispelling activities, along with enhancing immune function and improving cardiovascular health. In recent years, both fat-soluble and water-soluble steroidal saponins were isolated from the rhizomes of D. nipponica using silica gel column chromatography, thin layer chromatography and high performance liquid chromatography methods. Saponin and sapogenins are mainly responsible for most of the pharmacological effects of this plant. Further, the chemical components of the aboveground parts contain more than 10 kinds of phenanthrene derivatives. The present review summarizes the knowledge concerning the geographical distribution, chemical composition, pharmacological effects, toxicology studies and clinical applications of D. nipponica.

A series of D-A dyads and D-A-D triads molecular systems based on triphenylamine and 9-ethyl-carbarzole as donor (D) and BODIPY as acceptor (A) has been designed and synthesized. The optoelectronic properties including optical, electrochemical, and charge carrier mobility of these molecules have been investigated. We found that the D-A-D triads exhibited broader absorption, raising the HOMO energy levels and increase hole carrier mobilities. Analysis surface morphology revealed that BODIPY containing carbazole demonstrated smooth film and no macro phase aggregation was observed upon thermal annealing.

A series of azinesulfonamide derivatives of long-chain arylpiperazines with variable-length alkylene spacers between sulfonamide and 4-arylpiperazine moiety is designed, synthesized, and biologically evaluated. In vitro methods are used to determine their affinity for serotonin 5-HT_1A, 5-HT₆, 5-HT₇, and dopamine D₂ receptors. X-ray analysis, two-dimensional NMR conformational studies, and docking into the 5-HT_1A and 5-HT₇ receptor models are then conducted to investigate the conformational preferences of selected serotonin receptor ligands in different environments. The bent conformation of tetramethylene derivatives is found in a solid state, in dimethyl sulfoxide, and as a global energy minimum during conformational analysis in a simulated water environment. Furthermore, ligand geometry in top-scored complexes is also bent, with one torsion angle in the spacer (τ₂) in synclinal conformation. Molecular docking studies indicate the role of halogen bonding in complexes of the most potent ligands and target receptors.

Background: Radix Glycyrrhizae is the rhizome of Glycyrrhiza inflata Bat., Glycyrrhiza uralensis Fisch. or Glycyrrhiza glabra L. The present paper describes the isolation and the structural elucidation of three new dihydroisocoumarins obtained from the 70% EtOH extract of Radix Glycyrrhizae. And the cytotoxic activities of these new compounds were also evaluated using four cell lines, subsequently.

Results: A pair of new dihydroisocoumarin epimers ((3R,4S)-4,8-dihydroxy-3-methyl-1-oxoisochroman-5-yl)methyl acetate (1) and ((3R,4R)-4,8-dihydroxy-3-methyl-1-oxoisochroman-5-yl)methyl acetate (2) along with a new dihydroisocoumarin (3R,4R)-4,8-dihydroxy-3,5-dimethylisochroman-1-one (3) were isolated from Radix Glycyrrhizae. Their structures were elucidated on the basis of chemical and spectral analysis, including 1D, 2D NMR analyses, HR-ESI-MSand ECD calculation comparing with those of experimental CD spectra. Cytotoxic activities of the three compounds were evaluated using the HepG2, A549, LoVo and Hela cell lines, respectively. IC₅₀ values indicated compounds 1-3 exhibited moderate or less cytotoxic activity in vitro.

Conclusions: Dihydroisocoumarin is not the common components in Radix Glycyrrhizae, a series of dihydroisocoumarin were obtained in this plant could be a supplement to the chemical study of this plant.