Junhua Liu

Thiamine hydrochloride (VB1): an efficient promoter for the one-pot synthesis of benzo[4,5]imidazo[1,2-a]pyrimidine and [1,2,4]triazolo[1,5-a]pyrimidine derivatives in water medium

A straightforward and general method has been developed for the synthesis of benzo[4,5]imidazo[1,2-a]pyrimidine and [1,2,4]triazolo[1,5-a]pyrimidine derivatives by simply combining 2-aminobenzimidazole or 3-amino-1,2,4-triazole, aldehyde, and β-dicarbonyl compound in the presence of a catalytic amount of thiamine hydrochloride (VB1). The advantages of this method are the use of an inexpensive and readily available catalyst, easy workup, improved yields, and the use of water as the solvent that is considered to be relatively environmentally benign.

Reversal of P-gp and MRP1-mediated multidrug resistance by H6, a gypenoside aglycon from Gynostemma pentaphyllum, in vincristine-resistant human oral cancer (KB/VCR) cells

Multidrug resistance (MDR) to anticancer drugs is a major obstacle to successful chemotherapy in the treatment of cancers. Identification of natural compounds capable of circumventing MDR with minimal adverse side effects is an attractive goal. Here, we found that H6, a gypenoside aglycon from Gynostemma pentaphyllum, displayed potent anti-MDR activity. Average resistant fold (RF) of H6 is 1.03 and 1.04 in KB/VCR and MCF-7/ADR cells compared to their parental cells. H6 alone ranging from 2 μmol/l to 40 μmol/l (μM) did not display a significant anti-proliferative effect on KB/VCR cells and other cells, while the compound at these concentrations enhanced the cytotoxicity of vincristine (VCR) to KB/VCR cells. H6 showed a significant synergistic effect in combination with VCR. By quantification of sub-G(1) fraction cells, H6 also enhanced the VCR-induced apoptosis in a dose-dependent manner. The short time treatment with H6 increased the intracellular accumulation of rhodamine 123 (Rho123) and 5(6)-carboxyfluorescein diacetate (CFDA) in KB/VCR cells. Further studies showed that H6 treatment resulted in the decrease of the RNA transcript level of P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1) and breast cancer resistance protein (BCRP). H6 inhibited the function of P-gp by stimulating P-gp ATPase activity and decreased MRP1 expression with a blockade of STAT3 phosphorylation. These findings suggest that H6, a multi-targets reversal agent with no significant toxic effect, may be a potential candidate to circumvent the P-gp and MRP1-mediated MDR.

A catalyst-free reaction in water: synthesis of benzo[4,5]imidazo[1,2-a]pyrimido[4,5-d]pyrimidin-4(1H)-one derivatives

An environmentally benign and efficient method has been developed for the synthesis of a series of benzo[4,5]imidazo[1,2-a]pyrimido[4,5-d]pyrimidin-4(1H)-one derivatives in aqueous media under catalyst-free conditions by simply combining 2-aminobenzimidazole, aldehyde, and cyanoacetamide. The advantages of this method are that it is catalyst-free, has an easy workup, provides excellent yields, and uses water as the solvent which is considered to be relatively environmentally benign.

Potential AMPK activators of cucurbitane triterpenoids from Siraitia grosvenorii Swingle.

AMP-activated kinase (AMPK) as a key controller in the regulation of whole-body energy homeostasis, plays an important role in protecting the body from metabolic diseases. Recently, improved glucose, lipid utility and increased insulin sensitivity were observed on several diabetic rodent models treated with crude mogrosides isolated from the fruit of Siraitia grosvenorii Swingle, but the precise active compounds responsible for the anti-diabetic activity of this plant have not been clearly identified. In our current work, acid hydrolysis of crude mogrosides provided five new cucurbitane triterpenoids (1-4, 8), along with three known ones (5-7). The main aglycone mogrol (7) and compounds 4 and 8 were found to be potent AMPK activators in the HepG2 cell line. This result suggested AMPK activation by the mogroside aglycones 7 and 8 was proved to contribute at least partially to the anti-hyperglycemic and anti-lipidemic properties in vivo of S. grosvenorii.

Influence of high-temperature AIN buffer thickness on the properties of GaN grown on Si(111)

The influences of AlN buffer thickness on the optical and the crystalline properties of metalorganic chemical vapor deposition wurtzite GaN layers on Si(I 11) substrate have been investigated. High-resolution X-ray diffraction and photoluminescence measurement reveal that the thickness of AlN buffer exerts a strong influence on the distribution of dislocation and stress in GaN epilayer. The evidence is further reinforced by atomic force microscopic observation of AlN nucleation process. The optimum thickness of AlN buffer to effectively suppress Si diffusion has been determined by secondary-ion mass spectroscopy to be in the range of 13-20 nm. In addition, it is found that appropriate Si diffusion in AlN buffer helps to compensate the tensile strain in GaN, which subsequently improves the optical quality of GaN on Si(I 1, 1), and reduces the cracks over the GaN surface

Synthesis and biological evaluation of bufalin-3-yl nitrogen-containing-carbamate derivatives as anticancer agents.

A series of bufalin-3-yl nitrogen-containing-carbamate derivatives 3 were designed, synthesized, and evaluated for their proliferation inhibition activities against human cervical epithelial adenocarcinoma (HeLa) cell line. The structure-activity relationships (SARs) of this new series are described in this paper. Cytotoxicity data revealed that the C3 moiety had an important influence on cytotoxic activity. Compound 3i-HCl exhibited significant in vitro antiproliferative activity against the ten tested tumor cell lines, with IC50 values ranging from 0.30 to 1.09 nM. Furthermore, 3i-HCl can significantly inhibit tumor growth by 100% at the dose 2 mg/kg by iv, or 4 mg/kg by ig.

20(S)-Protopanaxadiol (PPD) analogues chemosensitize multidrug-resistant cancer cells to clinical anticancer drugs.

Novel 20(S)-protopanoxadiol (PPD) analogues were designed, synthesized, and evaluated for the chemosensitizing activity against a multidrug resistant (MDR) cell line (KBvcr) overexpressing P-glycoprotein (P-gp). Structure-activity relationship analysis showed that aromatic substituted aliphatic amine at the 24-positions (groups V) effectively and significantly sensitized P-gp overexpressing multidrug resistant (MDR) cells to anticancer drugs, such as docetaxel (DOC), vincristine (VCR), and adriamycin (ADM). PPD derivatives 12 and 18 showed 1.3-2.6 times more effective reversal ability than verapamil (VER) for DOC and VCR. Importantly, no cytotoxicity was observed by the active PPD analogues (5μM) against both non-MDR and MDR cells, suggesting that PPD analogues serve as novel lead compounds toward a potent and safe resistance modulator. Moreover, a preliminary mechanism study demonstrated that the chemosensitizing activity of PPD analogues results from inhibition of P-glycoprotein (P-gp) overexpressed in MDR cancer cells.

Synthesis and structure–activity relationships of boswellic acid derivatives as potent VEGFR-2 inhibitors

A series of AKBA derivatives were synthesized, and evaluated as potent VEGFR-2 inhibitors. The initial biological evaluation indicated that the introduction of C-24 amide group or a heterocycle at C-2,3 position effectively improved the potency. Further structure-activity relationship analysis showed that amide (7, 23, 25, and 26) and heterocycle (19, 34, and 36) substituted AKBA derivatives displayed more potential anti-proliferation activities than AKBA (1) on HUVECs that express high levels of VEGFR-2. Among all tested compounds, compounds 7 and 19 exhibited the best potency (IC₅₀: 2.36 and 2.13 μM) and obvious inhibitory activities with VEGFR-2 inhibition rates of 96% and 94% at 50 μM, respectively.

Cytotoxic cucurbitane triterpenoids isolated from the rhizomes of Hemsleya amabilis.

Two new cucurbitane triterpenoids, 7β-hydroxycucurbitacin F-25-O-acetate (1) and 2β,3β,20(S),26,27-pentahydroxy-16α,23(S)-epoxycucurbita-5,24-dien-11-one (2) along with eleven known cucurbitane triterpenoids (3-13, resp.) were isolated from the rhizomes of Hemsleya amabilis Diels. The chemical structures of the new isolated compounds were elucidated unambiguously by spectroscopic data analysis. The cytotoxic activities of the isolated cucurbitane triterpenoids were evaluated against the HeLa human cancer cell lines. Hemslecin A (5), the main ingredient of H. amabilis, exhibited the significant cytotoxicity with IC50 value of 0.389 μM.

Cytotoxic sesquiterpene lactone dimers isolated from Inula japonica.

Two new sesquiterpene lactone dimers, neojaponicone B (1) and inulanolide E (2) along with five known sesquiterpene lactone dimers (3-7, resp.) were isolated from the aerial parts of Inula japonica Thunb. The chemical structures of 1 and 2 were elucidated by detailed spectroscopic analysis. The relative configuration of 2 was confirmed by biomimetic transformation from the known sesquiterpene lactone dimer inulanolide A (3). The cytotoxicities of the isolated sesquiterpene lactone dimers were evaluated against 6T-CEM and Jurkat cell lines. All compounds showed potent cytotoxicities with IC50 value of 2.2-5.9μm.