Aromatic Amine and Chiral Phosphoric Acid Synergistic Catalyzed Cascade Reaction of Alkynylnaphthols with Aldehydes.

A novel approach using aromatic amines and chiral phosphoric acids in a synergistic catalytic cascade reaction of 2-alkynylnaphthols with aldehydes has been established. This method offers a direct route to preparing flavanone analogues with excellent stereoselectivity. Mechanistic studies reveal a sequential process involving addition, elimination, cyclization, and hydrolysis in which aromatic amines and chiral phosphoric acids play key roles via imine-enamine and hydrogen bonding models.

A novel conjunction of folate-targeted carbon nanotubes containing protohemin and oridonin-liposome loaded microbubbles for cancer chemo-sonodynamic therapy.

To facilitate targeting drug delivery and combined therapy, we constructed a novel drug carrier, in which oridonin-liposome containing microbubbles (LUMO) are covalently adhered to folic acid-conjugated multiwalled carbon nanotubes loaded with protohemin (FMTP) to form a novel conjugate (FMTP-LUMO). Oridonin (ORI) is used as a chemotherapeutic drug for chemotherapy (CHT), whereas protohemin (Ph) is applied in the field of sonodynamic therapy (SDT) as a sonosensitizer. In vitro release properties, cellular uptake and cytotoxicity in HepG-2 cells as well as in vivo antitumour effects in HepG-2 cell tumour-bearing mice submitted to chemo-sonodynamic therapy, SDT alone and CHT alone were evaluated upon ultrasound exposure. The results showed that the growth inhibition rates on FMTP-LUMO, FMTP, and LUMO were 95.4 ± 5.9%, 63.9 ± 7.4%, and 42.3 ± 2.9% in vitro, respectively. FMTP-LUMO exhibited strong binding to HepG-2 cells than MTP-LUMO. The chemo-sonodynamic therapy demonstrated a cooperative effect, resulting in significantly higher therapeutic efficacy for liver cancer. After treatment for 10 d, the tumour inhibition ratio for FMTP-LUMO exceeded to 90%, clearly higher than that of FMTP (42.8%) and LUMO (32.5%). Thus, FMTP-LUMO could serve as a highly effective drug carrier for chemo-sonodynamic therapy.

Geridonin, a novel derivative of oridonin, inhibits proliferation of MGC 803 cells both in vitro and in vivo through elevating the intracellular ROS.

OBJECTIVES: To study the antitumour activity of a novel derivative of oridonin named geridonin in vitro and in vivo. METHODS: MTT and colony formation assay were used to test the cytotoxicity of geridonin; apoptosis, cell cycle arrest and the levels of reactive oxygen species were measured by flow cytometry; JC-1 staining assay was used to examine the mitochondrial membrane potential; the MGC 803 xenograft model was established to evaluate the antitumour effect of geridonin in vivo; H&E staining was performed for the histological analysis. KEY FINDINGS: In vitro, geridonin remarkably inhibited proliferation of gastrointestinal cancer cells including oesophageal, gastric, liver and colon cancers. On oesophageal, gastric cancer cells, geridonin displayed strong cytotoxicity than that of oridonin. In gastric cancer MGC 803 cells, geridonin triggered apoptosis through the mitochondrial pathway depending on caspase. In addition, geridonin sharply reduced the formation of cell colony, increased the intracellular levels of ROS and induced cell cycle arrest at G2/M phase. In vivo, geridonin delayed the growth of MGC 803 xenograft in athymic mice without obvious loss of bodyweight. CONCLUSIONS: The novel derivative of oridonin, geridonin, inhibited the growth of human gastric cancer cells MGC 803 both in vitro and in vivo mainly via triggering apoptosis depending on elevating intracellular level of ROS.

Preparation and Sonodynamic Antitumor Effect of Protohemin-Conjugated Multiwalled Carbon Nanotubes Functionalized with Carboxylic Group.

Preclinical Research Sonodynamic therapy (SDT) is a cutting edge approach to treating cancer that involves necrosis and/or apoptosis. Multiwalled carbon nanotubes functionalized with carboxylic groups (MWCNTs-COOH) due their physicochemical structure represent a novel drug delivery system in the field of nanomedicine. The purpose of the research reported in this paper was to increase the antitumor potency and reduce the potential side effects of protohemin (Ph), a sonosensitizer for SDT, which was noncovalently encapsulated into MWCNTs-COOH (MWCNTs-Ph). The Ph loading efficiency in MWCNTs-COOH carrier was determined as approximately 68.8% (w/w). The growth inhibition rate of MWCNTs-Ph (Ph: 180 µg/mL) was approximately 95 ± 8.5%, whereas Ph-F (Ph: 180 µg/mL) inhibited 58 ± 4.5% of tumor cell. Ph (Ph: 180 µg/mL) alone had no antitumor effect in HepG-2 cells using ultrasound treatment at 1.0 MHz and 0.5 W/cm(2) for 100 s. Assessment of the antitumor effects of MWCNTs-Ph and Ph-F at day 11 after SDT showed that he tumor inhibition ratio for MWCNTs-Ph (6.18 × 10(-2) g·kg(-1) ·d(-1) ) was 82.8%, twice that of Ph-F (6.18 × 10(-2) g·kg(-1) ·d(-1) ) ay 41.8%. In conclusion, MWCNTs-Ph had increased antitumor efficiency and also decreased potential side effects. Drug Dev Res 77 : 152-158, 2016. © 2016 Wiley Periodicals, Inc.

Synthesis and analgesic activities of endomorphin-2 and its analogues.

Endomorphin-2 (1; H-Tyr-Pro-Phe-Phe-NH2; EM2) and its novel cyclic asparagine (cycloAsn) analogues, H-Tyr-cAsn(CHPh)-Phe-Phe-NH2 (2) and H-Tyr-cAsn(CHMe2)-Phe-Phe-NH2 (3), were synthesized via liquid-phase synthesis. The structures of the products and intermediates were characterized by IR, 1H-NMR, MS, and HR-MS analyses. The antinociceptive activity of EM2 and its cyclic asparagine analogues were assessed in AcOH-induced abdominal constriction tests in mice with i.p. injection. The results show that the antinociceptive activities of EM2 and its cyclic asparagine analogue 2 were higher than those of aspirine and meperidine. Analogue 2 was observed to be a stronger analgesic with dose-dependence than EM2. The test mice did not show any tendency to be addicted while administrated of analogue 2 repeatedly and regularly.