Ya Wu

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).

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 α-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.

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.

A novel Na+ coordination mediated supramolecular organogel based on isosteviol: water-assisted self-assembly, in situ forming and selective gelation abilities

A novel sodium sulfonate gelator self-assembles through water-assisted Na+ coordination to gelate halohydrocarbon solvents selectively with a Cgel as low as 0.1% w/v. In situ gel formation can be achieved by adding the relative sulfonic acid to an organic solvent–brine two-phase system at room temperature.

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.