Zhiguang Song

Apoptosis is Induced in Cancer Cells via the Mitochondrial Pathway by the Novel Xylocydine-Derived Compound JRS-15

The novel compound JRS-15 was obtained through the chemical modification of xylocydine. JRS-15 exhibited much stronger cytotoxic and pro-apoptotic activity than its parent compound in various cancer cell lines, with IC50 values in HeLa, HepG2, SK-HEP-1, PC-3M and A549 cells ranging from 12.42 to 28.25 μM. In addition, it is more potent for killing cancer than non-cancerous cells. Mechanistic studies showed that JRS-15 treatment arrested cell cycle at the G1/S phase, which further triggered the translocation of Bax and Bak to the mitochondria, resulting in mitochondrial membrane potential (MMP) depolarization and the subsequent release of cytochrome c and the second mitochondria-derived activator of caspase (Smac). The sequential activation of caspase-9 and caspase-3/7 and the cleavage of poly (ADP-ribose) polymerase (PARP) were observed following these mitochondrial events. Caspase-8, an initiator caspase that is required to activate the membrane receptor-mediated extrinsic apoptosis pathway was not activated in JRS-15-treated cells. Further analysis showed that the levels of the anti-apoptotic proteins Bcl-xL and XIAP were significantly reduced upon JRS-15 treatment. Furthermore, the caspase-9 inhibitor z-LEHD-fmk, the pan-caspase inhibitor z-VAD-fmk, and Bcl-xL or XIAP overexpression all effectively prevented JRS-15-induced apoptosis. Taken together, these results indicate that JRS-15 induces cancer cell apoptosis by regulating multiple apoptosis-related proteins, and this compound may therefore be a good candidate reagent for anticancer therapy.

Esterification and Chemoselective Synthesis of R-Tetrahydrothiazo-2-thione-4-carboxylic Esters Catalyzed by TiCl4

A series of esters of R -tetrahydrothiazo-2-thione-4-carboxylic acid[ R -TTCA] was synthesized by direct esterification of R -TTCA with alcohols (CH 3 OH, C 2 H 5 OH, n -C 3 H 7 OH, i -C 3 H 7 OH, n -C 4 H 7 OH, sec-C 4 H 9 OH) in the presence of TiCl 4 as the catalyst at room temperature without using any other solvent or dehydrant in high yields, 91. 6%–99. 1% for primary alcohols and 55%–80% for secondary alcohols. The catalyst has a strong chemoselective activity for the esterification of primary alcohols with R -TTCA in the presence of secondary alcohols. Owing to high yield, high chemoselectivity, and mild conditions used, this is an efficient method for the esterification of primary alcohols with R -TTCA.

The identification of molecular target of (20S) ginsenoside Rh2 for its anti-cancer activity

The 20S ginsenoside Rh2 (G-Rh2) effectively inhibits cancer cell growth and survival in both animal models and cell lines. However, its molecular targets and mechanism of action remain largely unknown. By screening for molecules that interact with (20S)G-Rh2 in a phage display assay, we have identified Annexin A2 as a potential target that mediates its anti-cancer activity. Isothermal titration calorimetry and a cellular thermal shift assay demonstrated that (20S)G-Rh2 directly bound to either recombinant or intracellular Annexin A2. This binding inhibited the interaction between Annexin A2 and the NF-кB p50 subunit, which attenuated the nuclear translocations of NF-кB p50 subunit and reduced the transactivation activity of NF-кB. Correspond to this result, (20S)G-Rh2 treatment significantly down-regulated the expression of IAPs (inhibitors of apoptosis), the well-established NF-кB targets that promote cell survival. Moreover, (20S)G-Rh2 synergized with Annexin A2 inactivation to promote apoptosis. Taken together, this study for the first time suggests a cellular target and a molecular pathway by which (20S)G-Rh2 inhibits cancer cell growth. As over-expression of Annexin A2 was evident in human hepatoma, (20S)G-Rh2 might be a promising natural compound for targeted liver cancer therapy.

Design and Synthesis of 3-Triazolo-coumarins and Their Applications in Scavenging Radicals and Protecting DNA

In this study, we synthesized a series of 3-triazolo-coumarins and evaluated their antioxidant activities respectively by two methods: trapping 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical(ABTS+·) and oxidation of DNA which was induced by Cu2+/glutathione(GSH), ·OH and 2,2′-azobis(2-amidinopropane hydrochloride)(AAPH). Among the nine 3-triazolo-coumarins, compounds 6c and 6f-6i were synthesized for the first time, which exhibited the capability of terminating radical propagation-chains in oxidation of DNA induced by AAPH. In this study, we found that phenethylamine moiety, hydroxyl and ortho-methoxy are the key groups to enhance the antioxidant activities of compounds.

Design, synthesis and antitumor activity in vitro of a series of 3-arylcoumarins

A new series of 7-substituted 3-arylcoumarins was designed, synthesized and evaluated as novel antitumor agents in vitro. It was found that several compounds of them exhibit activity in vitro against SK-HEP-1(hepatocellu- lar carcinoma), HepG2(hepatocellular carcinoma) and SGC7901(gastric carcinoma) cell lines to some extent. Moreover, compounds 5a, 5b, 6a and 6b have better activity against HeLa(cervical carcinoma) cell and their half maximal inhibitory concentration(IC50, μmol/L) values are less than 10.

Synthesis of Novel Thiazoline Catalysts and Their Application in Michael Addition Reaction

Several novel chiral thiazoline catalysts containing thiazoline, thiourea and proline were efficiently synthesized from commercially available L-cysteine. These ligands were subsequently applied to the asymmetric Michael reaction between cyclohexanone and various β-nitrostyrene. The result shows that the optimal catalyst for this reaction is ligand 18d, the organocatalyst with thiazoline, thiourea and chiral proline motif, which efficiently promotes the enantioselective conjugate addition of cyclohexanone to various nitroalkenes to yield the corresponding addition products in high to excellent yields with enantiomeric excess(e.e.) up to 95% and diastereoselectivity ratio(dr.) up to 99:1.

The interaction of serum albumin with ginsenoside Rh2 resulted in the downregulation of ginsenoside Rh2 cytotoxicity

Background Ginsenoside Rh2 (G-Rh2) is a ginseng saponin that is widely investigated because of its remarkable antitumor activity. However, the molecular mechanism by which (20S) G-Rh2 triggers its functions and how target animals avoid its cytotoxic action remains largely unknown. Methods Phage display was used to screen the human targets of (20S) G-Rh2. Fluorescence spectroscopy and UV-visible absorption spectroscopy were used to confirm the interaction of candidate target proteins and (20S) G-Rh2. Molecular docking was utilized to calculate the estimated free energy of binding and to structurally visualize their interactions. MTT assay and immunoblotting were used to assess whether human serum albumin (HSA), bovine serum albumin (BSA), and bovine serum can reduce the cytotoxic activity of (20S) G-Rh2 in HepG2 cells. Results In phage display, (20S) G-Rh2-beads and (20R) G-Rh2-beads were combined with numerous kinds of phages, and a total of 111 different human complementary DNAs (cDNA) were identified, including HSA which had the highest rate. The binding constant and number of binding site in the interaction between (20S)-Rh2 and HSA were 3.5 × 105 M−1 and 1, and those in the interaction between (20S) G-Rh2 and BSA were 1.4 × 105 M−1 and 1. The quenching mechanism is static quenching. HSA, BSA and bovine serum significantly reduced the proapoptotic effect of (20S) G-Rh2. Conclusion HSA and BSA interact with (20S) G-Rh2. Serum inhibited the activity of (20S) G-Rh2 mainly due to the interaction between (20S) G-Rh2 and serum albumin (SA). This study proposes that HSA may enhance (20S) G-Rh2 water solubility, and thus might be used as nanoparticles in the (20S) G-Rh2 delivery process.

Novel Chiral Bifunctional L‐Thiazoline‐Thiourea Derivatives: Design and Application in Enantioselective Michael Reactions

Several novel chiral bifunctional L-thiazoline-thiourea derivatives were easily synthesized from commercially available L-cysteine in high yield. These catalysts were subsequently applied to the enantioselective Michael addition of acetylacetone to β-nitrostyrenes. The products with S configuration were obtained in 98% enantiomeric excess (ee) when the L-thiazoline-thiourea derivatives were used. A plausible transition state model is proposed to explain the observed enantioselectivities.

Esterification and Selective Esterification in the Presence of TiCl4

Abstract A series of carboxylic acids was esterified to the corresponding esters with TiCl4 as catalyst at room temperature, in high yields. This catalyst was highly effective for the selective esterification of primary alcohols with carboxylic acids, in the presence of secondary alcohols, and for the selective esterification of saturated acid with alcohol in the presence of conjugated acid or aromatic acid. On account of the high yield, high chemoselectivity, mild condition, and being free of other dehydrants, this is an efficient method.

Synthesis and pharmacodynamics of ibuprofen-1-acetoxyethyl ester

Ibuprofen(IBU) and its derivatives are widely used in treating many diseases, such as depression, glomerulonephritis, fever caused by common cold or influenza, and rheumatoid arthritis. While in clinical trials, IBU was found to have many side effects. To weaken and prevent these side effects, a derivative called ibuprofen-1-acetoxyethyl ester was synthesized in this paper. The maximum concentration(cmax) in a shorter time was compared with IBU at the same dose.