Design, synthesis and biological evaluation of 1-aryldonepezil analogues as anti-Alzheimer's disease agents.

Aim: To design and synthesize a novel series of 1-aryldonepezil analogues. Materials & methods: The 1-aryldonepezil analogues were synthesized through palladium/PCy3-catalyzed Suzuki reaction and were evaluated for cholinesterase inhibitory activities and neuroprotective effects. In silico docking of the most effective compound was conducted. Results: The 4-tert-butylphenyl analogue exhibited good inhibitory potency against acetylcholinesterase and butyrylcholinesterase and had a favorable neuroprotective effect on H2O2-induced SH-SY5Y cell injury. Conclusion: The 4-tert-butylphenyl derivative is a promising lead compound for anti-Alzheimer's disease drug development.

[Box: see text].

Palladium-Catalyzed Synthesis and Anticancer Activity of Paclitaxel-Dehydroepiandrosterone Hybrids.

According to the activity-structure relationship of the C-13 side chain in paclitaxel or docetaxel, eighteen novel paclitaxel-dehydroepiandrosterone (DHEA) hybrids were designed and synthesized by Pd(II)-catalyzed Suzuki-Miyaura cross-coupling of 17-trifluoromethanesulfonic enolate-DHEA with different aryl boronic acids. The in vitro anticancer activity of the hybrids against a human liver cancer cell line (HepG-2) was evaluated by MTT assay, showing that most of these hybrids possessed moderate antiproliferative activity against the HepG-2 cancer cell line. Among these hybrids, three ones (7b, 7g, and 7i) with ortho-substituents in the phenyl group of the D-ring of DHEA analogues exhibited moderate anticancer activity. The optimal compound 7i showed superior anticancer activity against the HepG-2 cell line with an IC50 value of 26.39 µM.

Natural products as important tyrosine kinase inhibitors.

As an important source of drugs, natural products play an important role in the discovery and development of new drugs. More than 60% of anti-tumor drugs are closely related to natural products. At the same time, as the main cause of tumors, the abnormal activity of tyrosine kinase has become an important target for clinical treatment. Although, small molecule targeted drugs dominate the cancer treatment. Natural active products are driving the development of new tyrosine kinase inhibitors with their unique mode of action and molecular structure diversity. Obtaining new chemical entities with tyrosine kinase inhibitory activity from natural active products will bring new breakthroughs in the research of anticancer drugs. In this paper, different tyrosine kinases are mainly classified as targets, and natural products and derivatives which have been found to inhibit tyrosine kinase activity have been described. It is hoped that by analyzing the different aspects of the source, structural characteristics, mechanism of action and biological activity of these natural products, we will find new members that can be developed into drugs and promote the development of anti-tumor drugs.

Hydroxycinnamoylmalated flavone C-glycosides from Lemna japonica.

Three previously undescribed flavone C-glycosides (1-3), along with seven known ones (4-10), were isolated and characterized from the smallest flowering aquatic plant, Lemna japonica. On the basis of spectroscopic analysis and alkaline hydrolysis, compounds 1-3 were identified to be luteolin 6-C-(2″-O-trans-caffeoyl-d-malate)-ß-glucoside (1), apigenin 6-C-(2″-O-trans-caffeoyl-d-malate)-ß-glucoside (2), and luteolin 6-C-(2″-O-trans-coumaroyl-d-malate)-ß-glucoside (3). Compounds 1-3 are characteristic of a trans-coumaroyl-d-malate or trans-caffeoyl-d-malate linked to C-2″ of the glucose, which was reported for the first time. Compounds 1-3 exhibited weak cytotoxicity against HepG-2, SW-620, and A-549 cell lines, with IC50 values between 42.5 and 19.2µg/ml, and moderate antioxidant activity. Meanwhile compound 3 displayed moderate nematocidal activity with an EC50 value of 1.56mg/ml.

Cytotoxic triterpenoid saponins from Clematis tangutica.

Eight previously undescribed oleanane-type triterpenoid saponins, clematangoticosides A-H, together with eight known saponins, were isolated from the whole plants of Clematis tangutica (Maxim.) Korsh. Their structures were elucidated by extensive spectroscopic analysis, in combination with chemical methods (acid hydrolysis and mild alkaline hydrolysis). Clematangoticosides D-G were found to be unusual 23, 28-bidesmosidic glycosides. The cytotoxic activities of all of the isolated saponins were evaluated against the four human cancer cell lines SGC-7901, HepG2, HL-60 and U251MG. Clematoside S, sapindoside B, kalopanax saponin A, and koelreuteria saponin A exhibited cytotoxicity against all of the test cancer cell lines with IC50 values in the range of 1.88-27.20 µM, while clematangoticoside D and F showed selective cytotoxicity against SGC-7901 with IC50 values of 24.22 and 21.35 µM, respectively.

[Chemical Constituents from Przewalskia tangutica].

Objective: To study the Chemical constituents from Przewalskia tangutica. Methods: The compounds were isolated and identified from n-butanol extract of Przewalskia tangutica by various chromatographic and spectral techniques. Results: Twelve polar compounds were isolated and identified as scopolin( 1),fabiatrin( 2),rutin( 3),queroetin-3-O-rutinoside-7-O-ß-D-glucopyranoside( 4),protocatechuate( 5),vanillic acid( 6),thymine( 7),uracil( 8),cytosine( 9),adenine( 10),uridine( 11) and adenosine( 12). Conclusion: Compounds 3 ~ 5,8 ~ 12 are obtained from Przewalskia tangutica for the first time.

Analysis of cipadesin limonoids from Cipadessa cinerascens using electrospray ionization quadrupole time-of-flight tandem mass spectrometry and quantum chemical calculations.

RATIONALE: Limonoids, a class of tetranortriterpenoids, exhibit various biological effects, such as insect antifeedant and growth regulating activities, antimicrobial activity, potent cell adhesion inhibitory effects, antimalarial activity, anticancer activities, and antioxidant activity. The potential application brings the need for reliable, fast and low-cost analysis of this class of compounds. METHODS: Six cipadesin limonoids (1-6), including a pairs of isomers, from leaves and barks of Cipadessa cinerascens were investigated by electrospray ionization quadrupole time-of-flight tandem mass spectrometry (ESI-QTOF-MS/MS) in positive-ion mode. Characteristic processes were further studied by theoretical calculations. RESULTS: 1,3-Hydrogen rearrangement might play a significant role in the cleavage of -O- bridge bond in ring B and further produces some characteristic ions. For [M + Na](+) precursor ions, the product ion at m/z 133 might indicate the structure of ring A and the losses of CO(2) and AcOH occur readily. Interestingly, the radical product ion at m/z 460 from [M + Na](+) ions seems to be the characteristic ion for compound 1. A deuterium-labeling experiment supported the processes forming the radical ion. For [M + NH(4)](+) ions, high-abundance product ions resulting from sequential loss of AcOH can be observed. In addition, a pairs of isomers was unambiguously differentiated based on MS or MS/MS spectra. CONCLUSIONS: In summary, sufficient information obtained from fragmentation experiments of [M + Na](+), [M + NH(4)](+) or [M + H](+) precursor ions is especially valuable for rapid identification of these limonoids or their metabolites in complex mixtures. The high-abundance radical product ion is of scientific interest.

Brevianamide J, a new indole alkaloid dimer from fungus Aspergillus versicolor.

Brevianamide J (1), a new indole alkaloid dimer, was isolated together with four new diketopiperazine alkaloids (brevianamide K-N, 2-5) from the solid-state fermented culture of Aspergillus versicolor. Their structures were elucidated on the basis of spectral data. X-ray crystallographic analysis confirmed the structures of 1 and 4.

Determination of daunomycin in human plasma and urine by using an interference-free analysis of excitation-emission matrix fluorescence data with second-order calibration.

Daunorubicin (DNR) is a significant antineoplastic antibiotic, which is usually applied to a chemotherapy of acute lymphatic and myelogenous leukaemia. Unfortunately, cardiotoxicity research in animals has indicated that DNR is cardiotoxic. Therefore, it is important to quantify DNR in biological fluids. A new algorithm, the alternating fitting residue (AFR) method, and the traditional parallel factor analysis (PARAFAC) have been utilized to directly determine DNR in human plasma and urine. These methodologies fully exploit the second-order advantage of the employed three-way fluorescence data, allowing the analyte concentrations to be quantified even in the presence of unknown fluorescent interferents. Furthermore, in contrast to PARAFAC, more satisfactory results were gained with AFR.