Development of actein derivatives as potent anti-triple negative breast cancer agents.

Actein is a natural triterpenoid glycoside, isolated from the rhizomes of Cimicifuga foetida, which have been demonstrated to be potential in the treatment of breast cancer previously. Herein, we described the design and synthesis of a series of actein derivatives as anti-triple negative breast cancer (TNBC) inhibitors. Of which, the most promising derivative 27 exhibited significant inhibitory activity against human TNBC cell lines HCC1806 and MDA-MB-231, with IC50 values of 2.78 and 9.11 µM, respectively. Structure-activity relationships of actein derivatives were also discussed. Moreover, preliminary mechanism investigation revealed that 27 significantly inhibited cancer cell proliferation via cell cycle arrest at S phase. In addition, western blot analysis showed that the activation of MAPK signaling pathway might contribute to derivative 27 induced cell death. Overall, these results indicate that 27 has the potential to be developed as a lead compound and compounds with the actein scaffold are a promising novel class of inhibitors to treat TNBC.

Chemical Synthesis Enables the Configurational Determination of Myristriol, a Highly Oxygenated Phenylpropanoid from Myristica fragrans Houtt.

A new phenylpropanoid, myristriol (1), along with 11 known ones were isolated from the seed kernel of Myristica fragrans Houtt. Their chemical structures were clearly elucidated by extensive spectroscopic analysis. In which, the relative configuration of 1 was finally determined as erythro-1 by comparison the NMR data of two synthetic erythro- and threo-diastereoisomers with that of natural 1.

Design, synthesis, and anti-triple negative breast cancer activity of novel Toosendanin derivatives.

Toosendanin (TSN) is a natural anti-cancer compound that is isolated from the traditional Chinese herbal Melia toosendan Sieb et Zucc. However, the research effect of TSN in the treatment of Triple negative breast cancer (TNBC) is still far from ideal. In this work, we investigated TSN and its derivatives in terms of their actions against MDA-MB-231 and HCC1806 TNBC cell lines. The results indicated that TSN and its derivative 11 showed excellent antitumor activity. Preliminary mechanistic studies showed that both compounds TSN and 11 induced S-phase arrest and G2/M phase cell number decrease in HCC1806 cells. Also, TSN and 11 significantly reduced the protein level of the well-known cancer suppressor gene p53, reduced the phosphorylation of AKT and ERK, and also induced the accumulation of phosphorylated p38 and p21.

Aerobic Copper-Catalyzed Intramolecular Cascade Oxidative Isomerization/[4+4] Cyclization of 2,2'-Disubstituted Stilbenes.

An aerobic copper-catalyzed cascade oxidative isomerization/[4+4] cyclization of 2,2'-disubstituted stilbenes is described. Under the mild CuCl/DBED/air catalytic system, various 5,10-heteroatom-containing tetrahydroindeno[2,1-a]indenes were efficiently prepared through the difunctionalizations of alkenes in a highly atom economic manner. Mechanistic investigations suggested the bicyclic product was likely formed through a sequence of rapid single-electron oxidation/[4+4] cyclization from 2,2'-disubstituted stilbene. The antarafacial manner of the thermally allowed [4+4] cyclization was further proven by series of control experiments and density functional theory calculations. Our findings provide an important addition to the aerobic copper-catalyzed oxidative cyclization.

[Association of single nucleotide polymorphism on chromosome 12q24.31 with susceptibility to coronary artery disease].

OBJECTIVE: To determine whether the single nucleotide polymorphism (SNP) on chromosome 12q24.31(rs2259816) is associated with coronary artery disease (CAD) in Han population of southwest China. METHODS: A case-control association study with 592 unrelated patients with coronary artery disease and 463 normal controls from Chinese Han population was performed. Genotype for the SNP on chromosome 12q24.31 (rs2259816) was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: The genotypes of AA, AC, CC were both detected in the coronary artery disease group and the control group. The frequencies of A allele were 49.5% in case group and 43.8% in control group, showing statistically significant difference(OR=1.129, 95%CI:1.029-1.239, P=0.010). CONCLUSION: The replication study showed that the genetic polymorphism in rs2259816 is associated with coronary artery disease in Han population of southwest China.

[Association of single nucleotide polymorphism in rs174570 with coronary heart diseases in Han Chinese populations].

OBJECTIVE: To investigate the association between coronary heart diseases and single nucleotide polymorphism (SNP) in rs174570 in Han Chinese Populations. METHODS: A case-control study was undertaken in Han Chinese in Sichuan province, with 264 patients with coronary heart diseases and 303 normal controls. The genotypes of SNP in rs174570 were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: The genotypes of CC/CT/TT were detected in both case and control groups. No significant differences in the frequencies of the three genotypes were found between the two groups. The qualitative and quantitative analyses of the coronary angiography showed no significant differences in the patients with coronary heart diseases with the three genotypes. In the normal controls, high frequencies of C allele were associated with higher levels of low density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) (P < 0.05). CONCLUSIONS: Genetic polymorphism in rs174570 is not associated with the development and severity of coronary heart diseases despite its influences on serum LDL-C levels in Han Chinese Populations.