Design, Synthesis, and Biological Activity of Novel Triketone-Containing Phenoxy Nicotinyl Inhibitors of HPPD.

4-Hydroxyphenylpyruvate dioxygenase (HPPD) is a crucial target enzyme in albino herbicides. The inhibition of HPPD activity interferes with the synthesis of carotenoids, blocking photosynthesis and resulting in bleaching and necrosis. To develop herbicides with excellent activity, a series of 3-hydroxy-2-(6-substituted phenoxynicotinoyl)-2-cyclohexen-1-one derivatives were designed via active substructure combination. The title compounds were characterized via infrared spectroscopy, 1H and 13C nuclear magnetic resonance spectroscopies, and high-resolution mass spectrometry. The structure of compound III-17 was confirmed via single-crystal X-ray diffraction. Preliminary tests demonstrated that some compounds had good herbicidal activity. Crop safety tests revealed that compound III-29 was safer than the commercial herbicide mesotrione in wheat and peanuts. Moreover, the compound exhibited the highest inhibitory activity against Arabidopsis thaliana HPPD (AtHPPD), with a half-maximal inhibitory concentration of 0.19 µM, demonstrating superior activity compared with mesotrione (0.28 µM) in vitro. A three-dimensional quantitative structure-activity relationship study revealed that the introduction of smaller groups to the 5-position of cyclohexanedione and negative charges to the 3-position of the benzene ring enhanced the herbicidal activity. A molecular structure comparison demonstrated that compound III-29 was beneficial to plant absorption and conduction. Molecular docking and molecular dynamics simulations further verified the stability of the complex formed by compound III-29 and AtHPPD. Thus, this study may provide insights into the development of green and efficient herbicides.

[Biological Characteristics and Therapeutic Efficacy of 103 Patients with Acute Erythroleukemia].

OBJECTIVE: To investigate the biological characteristics and therapeutic efficacyt of acute erythroleukemia (AEL,AML-M6). METHODS: Blood cell count, liver function, lactate dehydrogenase level, coagulation, morphology, immunology, cell genetics and molecular biology were retrospectively analyzed in 103 cases of acute erythroleukemia patients admitted in our department from May 2016 to June 2009. The therapeutic efficacy was observed by means of remission rate, relapse rate, relapse-free survival and overall survival. RESULTS: The medians of white blood cells, granulocyte, hemoglobin and platelet were 3.04×109/L, 0.67×109/L, 66 g/L, and 45×109/L,respectively. Nucleated red blood cells were found in the peripheral blood smears from 71.1% of AEL patients. None of the patients showed abnormal coagulation function. Flow cytometry analysis indicated that CD13 (93.5%),CD117(89.1%), HLA-DR(87.0%), and CD34 (80.0%) were highly expressed in AEL, and lymphoid antigens of CD4 (42.9%) and CD7(28.9%) were expressed in partial patients. Karyotype analysis in 82 patients showed 52.4% (43/82) normal karyotype, 41.5% (34/82) abnormal karyotype, and 6.1% (5/82) failed tests. In the 34 cases with abnormal karyotype, there were 14(41.2%) cases with simple chromosomal abnomality and 20(58.8%) cases with complex karyotype. The positive rate of fusion gene accounted for 16.7% in 60 patients, and the gene mutations accounted for 77.8% in 27 patients. Among 103 cases of AEL, 81 cases were treated with chemotherapy, but 66 cases can be used for therapeutic analysis, as a results the total complete remission rate derived from 2 courses of treatment was 45.5% (30/66). The relapse rate was 36.7% (11/30), and the median relapse time was 15.5 months (6.2-50 months). The median survival time of 66 patients for therapeutic analysis was 29 months. The median survival time of CR patients was very significantly longer than that of the non-CR patients(P=0.001). The 5 year survival rate of CR patients was 65%, the median time of relapse-free survival (RFS) was 46.2 months and 3-years RFS was 58%. CONCLUSION: AEL is characterized by the highly expressed CD34 antigen, and complex karyotype. Although AEL has lower CR rate and poor prognosis, CR patients can achieve long-term survival and have good quality of life.

[Effect of bcl-2 siRNA on apoptosis of Burkitt's lymphoma cell line CA46].

The aim of this study was to investigate the effect of bcl-2 siRNA on bcl-2 gene expression and apoptosis of lymphoma cell line CA46. A siRNA was designed and synthesized. Then siRNA was transfected into CA46 cells by cationic liposome. At 48 hours after transfection, apoptosis and mitochondria transmembrane potential of CA46 cells were detected by flow cytometry, the expression of bcl-2 mRNA and BCL-2 protein in CA46 cells were detected by RT-PCR and flow cytometry respectively. The results showed that at 48 hours after transfection, apoptosis of CA46 cells occurred, mitochondria transmembrane potential changed. The expression of bcl-2 mRNA and BCL-2 protein in CA46 cells decreased significantly. In conclusion, bcl-2 siRNA depresses the expression of bcl-2 gene in CA46 cells specifically, then changes the mitochondria transmembrane potential, resulting in apoptosis of CA46 cells.