Syntheses, cytotoxic activity evaluation and HQSAR study of 1,2,3-triazole-linked isosteviol derivatives as potential anticancer agents.

A series of novel 1,2,3-triazole-linked isosteviol derivatives were designed and synthesized via Huisgen-click reaction. Their cytotoxicities in vitro against HCT-116 and JEKO-1 cells were screened. The preliminary bioassays indicated that most of the title compounds exhibited noteworthy cytotoxic activities. Particularly, the compound 10b revealed the most potent inhibitory activities against HCT-116 cells with IC50 value of 2.987±0.098µM, which was better than that (3.906±0.261µM) of positive control cisplatin. On the basis of these bioactivity data, hologram quantitative structure-activity relationship (HQSAR) was performed, and a statistically reliable model with good predictive power (r2=0.848, q2=0.544 and R2pred=0.982) was achieved. Additionally, the contribution maps derived from the optimal model explained the individual atomic contributions to the activity for each molecule.

Two phenyls are better than one or three: synthesis and application of terminal olefin-oxazoline (TOlefOx) ligands.

A novel terminal olefin-oxazoline ligand was introduced into rhodium-catalyzed asymmetric conjugate addition of arylboronic acids to enones and gave excellent enantioselectivities. The two phenyls proved better than one or three in ligand evaluations.

Efficient access to cis-decalinol frameworks: copper(i)-catalyzed borylative cyclization of allene cyclohexanediones.

Cu-catalyzed borylative cyclization of allene cyclohexanediones has been described through a tandem ß-borylation and intramolecular allylic addition process, affording borylated cis-decalinols with excellent yields and diastereoselectivities. A good enantioselectivity is also achieved in the asymmetric version. The hemiboronate group in the cyclization products could be subjected to several useful transformations.

Copper-catalyzed asymmetric allylation of chiral N-tert-butanesulfinyl imines: dual stereocontrol with nearly perfect diastereoselectivity.

Copper-catalyzed asymmetric allylation of chiral N-tert-butanesulfinyl imines has been described. Dual stereocontrol, through the combination of a chiral auxiliary and a chiral copper complex, has played an important role in achieving the nearly perfect diastereoselectivities (all dr > 99 : 1), especially for ketimine substrates.

Highly enantioselective Michael addition promoted by a new diterpene-derived bifunctional thiourea catalyst: a doubly stereocontrolled approach to chiral succinimide derivatives.

A doubly stereocontrolled organocatalytic asymmetric Michael addition to the synthesis of substituted succinimides is described. Starting from aldehydes and maleimides, both enantiomers of the succinimides could be obtained in high to excellent yields (up to 98%) and enantioselectivities (up to 99%) when one of the two special chiral diterpene-derived bifunctional thioureas was individually used as a catalyst. Moreover, these catalysts can be efficiently used in large-scale catalytic synthesis with the same level of yield and enantioselectivity.

Synthesis and in vitro cytotoxic activity evaluation of novel heterocycle bridged carbothioamide type isosteviol derivatives as antitumor agents.

Two series of novel carbothioamide-substituted pyrazole and isoxazolidine derivatives were facilely prepared by functional interconversions in ring D of the tetracyclic diterpene isosteviol. The in vitro cytotoxic activities against four human tumor cell lines were evaluated. Our results indicated that carbothioamide-substituted pyrazole derivatives exhibited noteworthy cytotoxic activities. Specifically, compound 12p (IC(50)=6.51 µM) had the most potent cytotoxicity against Raji cell, which may be exploitable as a lead compound for the development of potent antitumor agents.

D-ring modified novel isosteviol derivatives: design, synthesis and cytotoxic activity evaluation.

A series of polyhydric, amino alcohol and tricyclic derivatives were facilely synthesized by D-ring modification of isosteviol. These compounds were screened for their cytotoxic activities against four human tumor cell lines in vitro. Among them, the 15-α-aminomethyl-16-ß-hydroxyl isosteviol 23 exhibits significant cytotoxicity superior to the positive control (cisplatin) against EC9706, PC-3 and HCT-116 cell lines.

Ethyl ent-15α-[(2-nitro-benz-yloxy)meth-yl]-16-oxobeyeran-20-oate.

In the title compound, C(30)H(41)NO(6), the three six-membered rings adopt chair conformations and the stereochemistry of the A/B and B/C ring junctions are trans. The five-membered ring D adopts an envelope conformation, with the methyl-ene C atom as the flap. The title compound was synthesized via esterification, Tollens reaction, 1,5-hydride shift from the natural tetracyclic diterpenoid isosteviol.

Ethyl ent-15α-[(2-meth-oxy-benz-yloxy)meth-yl]-16-oxobeyeran-20-oate.

The title compound, C(31)H(44)O(5), was synthesized from isostev-iol (systematic name: ent-16-ketobeyeran-19-oic acid). In the mol-ecule, the three six-membered rings adopt chair conformations and the stereochemistry of the A/B and B/C ring junctions are trans. The five-membered ring D adopts an envelope conformation with the methyl-ene C atom as the flap.

Multifunctional Photocatalytic Filter Paper Based on Ultralong Nanowires of the Calcium-Alendronate Complex for High-Performance Water Purification.

Semiconductor photocatalysts and membrane separation technology have been widely used in the field of water treatment. Usually, the particles of traditional semiconductor photocatalysts are easy to aggregate, difficult to separate from the liquid phase after photocatalysis, and may even cause secondary pollution. On the other hand, the membrane separation technology is also facing the problem of sharp decreases in removal efficiency and water flux caused by the membrane fouling. However, it is an attractive and promising solution to combine two technologies of photocatalysis and membrane separation for high-performance water treatment. In this work, we have developed the calcium oleate precursor solvothermal method to synthesize ultralong nanowires (UNWs) of Ca-alendronate (Ca-ALN) complex for the first time. Experimental results and data analysis indicate that the as-prepared Ca-ALN ultralong nanowires are an n-type semiconductor with an energy band gap of 3.41 eV. A new type of multifunctional photocatalytic filter paper has been developed based on ultralong nanowires of Ca-ALN complex (Ca-ALN-UNWs) and cellulose fibers (CFs). The as-prepared Ca-ALN-UNW/CF photocatalytic filter paper exhibits multifunctions of photocatalysis, adsorption, and filtration, which can be used for high-performance treatment of the wastewater containing various pollutants such as heavy-metal ions, dyes, antibiotics, and bacteria. The active oxygen species produced by the Ca-ALN-UNW/CF photocatalytic filter paper under light illumination are determined by electron spin resonance, and the energy band gap and photoelectric properties of the material are tested by ultraviolet-visible diffuse reflectance spectroscopy and electrochemical workstation. The pure water flux of the Ca-ALN-UNW/CF photocatalytic filter paper is very high, which can reach 2230.5 L m-2 h-1 under a working pressure of 0.1 MPa. The Ca-ALN-UNW/CF photocatalytic filter paper is promising for various applications such as highly efficient water purification and in the biomedical field.

Stereoselective synthesis of 15- and 16-substituted isosteviol derivatives and their cytotoxic activities.

By means of functional interconversions in ring D of the tetracyclic diterpene isosteviol (ent-16-ketobeyeran-19-oic acid 1), various 15- and 16-substituted isosteviol derivatives were stereoselectively prepared. The cytotoxic activities in vitro of these new isosteviol derivatives were investigated, and some of them showed noteworthy activities against B16-F10 melanoma cells.

Stereoselective synthesis of bioactive isosteviol derivatives as alpha-glucosidase inhibitors.

Considerable interest has been attracted in isosteviol and its derivatives because of their large variety of pharmacological activities. In this project, a series of novel compounds containing hydroxyl, hydroxymethyl group and heteroatom-containing frameworks fused with isosteviol structure were synthesized and evaluated as alpha-glucosidase inhibitors, aimed at clarifying the structure-activity correlation. The results indicated that these isosteviol derivatives were capable of inhibiting in vitro alpha-glucosidase with moderate to good activities. Among them, indole derivative 15b exhibited the highest activities and thus may be exploitable as a lead compound for the development of potent alpha-glucosidase inhibitors.

(S)-5-(l-Menth-yloxy)-5-[(2R,3R)-2-(l-menth-yloxy)-5-oxotetra-hydro-furan-3-yl]furan-2(5H)-one.

In the title compound, C(28)H(44)O(6), the two five-membered rings form a dihedral angle of 6.7 (1)°. In the crystal structure, weak inter-molecular C-H⋯O hydrogen bonds link mol-ecules into layers parallel to (101).

Synthesis, cytotoxic activity, and 2D- and 3D-QSAR studies of 19-carboxyl-modified novel isosteviol derivatives as potential anticancer agents.

Two series of novel acylthiosemicarbazide and oxadiazole fused-isosteviol derivatives were synthesized based on the 19-carboxyl modification. The target compounds were evaluated for their cytotoxicities against three cancer cell lines (HCT-116, HGC-27, and JEKO-1) using an MTT assay. Lead compounds from the acylthiosemicarbazides (4) showed IC50 values in the lower micromolar range. For example, compounds (4i, 4l, 4m, 4r, and 4s) exhibited significant inhibitory activities against the three cell lines with IC50 values of 0.95-3.36 µm. Furthermore, 2D-HQSAR and 3D-topomer CoMFA analyses were established, which could be used to develop second generation of isosteviol derivatives as anticancer agents.

Synthesis, cytotoxic activity evaluation and HQSAR study of novel isosteviol derivatives as potential anticancer agents.

A series of novel isosteviol derivatives bearing amino alcohol and thiourea fragments have been stereo-selectively synthesized and screened for their in vitro cytotoxic activities against three human cancer cell lines (HCT-116, HGC-27 and JEKO-1). The results demonstrated that these compounds exhibited prominent cytotoxicities. Especially, the compound Iw displayed the most potent anticancer activities against HCT-116 cell with IC50 value of 1.450 µM. On the basis of this bioassay results, these derivatives were further investigated by the hologram quantitative structure-activity relationship (HQSAR) technique. The optimal HQSAR model with q(2) = 0.663, r(2) = 0.895, SEE = 0.179 was generated using A/B/H/Ch as fragment distinction parameters and 4-7 as fragment size. This model was employed to predict the cytotoxic activities of test set compounds, and the predicted values were in good agreement with the experimental results. The contribution maps derived from the optimal model explained the individual atomic contribution to the total activity of single molecule.

Design and stereoselective synthesis of novel isosteviol-fused pyrazolines and pyrazoles as potential anticancer agents.

Two series of novel isosteviol-fused pyrazoline and pyrazole derivatives were facilely synthesized via intramolecular 1,3-dipolar cycloaddition and condensation reaction, respectively. All compounds were characterized by NMR, IR and HRMS spectra. The stereochemistry of compounds 9b, 10, 11a and 11v were further confirmed by X-ray crystallographic analysis. The antiproliferative activities of the structurally related pyrazoline and pyrazole derivatives were tested in vitro on four human malignant cell lines (SGC 7901, A549, Raji and HeLa): Our results revealed that isosteviol-fused pyrazole derivatives exhibited noteworthy cytotoxic activities. Among them, 2,4-di-Cl-phenylpyrazole derivative 11t displayed better cytotoxities with IC50 values: 2.71, 3.18, 1.09 and 13.52 µM against SGC 7901, A549, Raji and HeLa, respectively, compared to cisplatin (IC50 values: 7.56, 17.78, 17.32 and 14.31 µM, respectively).

Chiral counteranion synergistic organocatalysis under high temperature: efficient construction of optically pure spiro[cyclohexanone-oxindole] backbone.

The combination of a cinchona-based chiral primary amine and a BINOL-phosphoric acid has been demonstrated as a powerful and synergistic catalyst system for the double Michael addition of isatylidene malononitriles with α,ß-unsaturated ketones, to provide the novel chiral spiro [cyclohexane-1,3'-indoline]-2',3-diones in high yields (88-99%) with excellent diastereo- and enantioselectivities (94:6-99:1 dr's, 95-99% ee's).

Synthesis and cytotoxicity of novel fatty acid-nucleoside conjugates.

N(3)-Hydroxyethyltegafur (3) was synthesized in 91.0% yield under a new condition. A series of novel fatty acid esters of 3 were synthesized. These fatty acid-nucleoside conjugates have shown cytotoxicities against Ec9706 cells and A549 cells, and the structure activity relationship was discussed.

Modified ant colony optimization algorithm for variable selection in QSAR modeling: QSAR studies of cyclooxygenase inhibitors.

A new version of an ant colony optimization (ACO) algorithm has been proposed. A modified ACO algorithm is proposed to select variables in QSAR modeling and to predict inhibiting action of some diarylimidazole derivatives on cyclooxygenase (COX) enzyme. As a comparison to this method, the evolution algorithm (EA) was also tested. Experimental results have demonstrated that the modified ACO is a useful tool for variable selection that needs few parameters to be adjusted and converges quickly toward the optimal position.