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??OBJECTIVE To research the effect of new L-phenylalanine derivatives on acetylcholinesterase(AChE) activity. METHODS New L-phenylalanine derivatives were synthesized from substituted 2-bromo-1-acetophenones by four steps reaction, and their inhibitory activities on AChE were measured by Ellman method in vitro. RESULTS The evaluation results showed that most derivatives possessed AChE inhibitory effect and the activity of compound 8b was the most potent with an IC₅₀ value of 8.73??10^-6 mol??L^-1, which was more potent than that of rivastigmine; moreover, compound 8b had no inhibitory activities to BuChE. CONCLUSION The inhibitory activities of new L-phenylalanine derivatives on acetylcholinesterase are worth studying further.
     

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??OBJECTIVE To synthesize 5-substituted indole-3-deoxypodophyllotoxin derivatives and study their antitumor activity. METHODS The target compounds were synthesized through a series of reactions and their anti-tumor activity in vitro were evaluated against Hela, K562 and K562/A02 cell lines by MTT as assay. RESULTS Ten target compounds were synthesized and confirmed by ¹H-NMR, ¹³C-NMR, and HR-ESI-MS. All the target compounds had different degrees of cytotoxic activity in vitro. Most of the compounds had significant anti-MDR activity in vitro. CONCLUSION 5-Substituted indole-3-deoxypodophyllotoxin derivatives have good antitumor activity and worth of further study.     

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??OBJECTIVE To synthesize the derivatives of 8-amino benzofuran[3,2-d]pyrimidine and study their anticancer activities.METHODS The target compounds were synthesized through a series of reactions, and their anticancer activities in vitro were evaluated against COLO205, MCF-7 and K562 cell lines by MTT as assay. RESULTS Nine title compounds were synthesized and confirmed by EI-MS,¹H-NMR and ¹³C-NMR.Compounds 2, 3d and 5c had good inhibition effect against COLO205, MCF-7 and K562 cells.The inhibition rates of compound 5c against COLO205, MCF-7 and K562 cells were 99.58%,78.75% and 98.68% respectively at 10^-4 mol??L^-1. CONCLUSION The anticancer activity of benzofuran[3,2-d] pyrimidine derivatives is worthy of further study.     

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??OBJECTIVE To investigate the potential anticancer effect of combretastatin A4 liposomes (SSL-CA4) in destruction of vascular mimicry (VM) in MDA-MB-231 breast cancer cells in vitro. METHODS The in vitro inhibitory effect and blocking wound-healing effect of SSL-CA4 were investigated. The VM destruction of SSL-CA4 was evaluated in three dimensional matrigel culture model in MDA-MB-231 cells. The in vitro inhibitory test showed that the maxium inhibition ratio of SSL-CA4 on MDA-MB-231 cells was close to 50%. SSL-CA4 blocked the wound-healing of MDA-MB-231 cells, which was similar to free CA4. RESULTS SSL-CA4 could inhibit the formation of VM in vitro via inhibition on the VM channel indicators including hypoxia-inducible factor (HIF-??), vascular endothelial-cadherin (VE-Cad), and matrix metallopeptidases (MMP-2). The inhibition on indicators of SSL-CA4 was significantly higher than CA4 treatment groups (P<0.05). CONCLUSION SSL-CA4 has significant anticancer activity via inhibition of VM in MDA-MB-231 cell line.     

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??OBJECTIVE To investigage the effects of celastrol-triggered HeLa cells autophagy and the molecular mechanisms in vitro and in vivo. METHODS The antiproliferative effect of celastrol was detected using MTT assay. Apoptotic rate and cell cycle were evaluated using flow cytometric analysis. Autophagy was detected using fluorescence microscope. Protein expression was evaluated using Western blotting. Tumor growth was evaluated by subcutaneous xenograft model in vivo. RESULTS Celastrol inhibited HeLa cells proliferation and induced HeLa cells autophagy and cell cycle arrest at G₀/G₁ phase, but not induced HeLa cell apoptosis in vitro. The protein expression of Beclin 1 was up-regulated and the conversion from LC3 ?? to LC3 ?? was increase in HeLa cells in vitro after treatment with celastrol. Moreover, celastrol promoted the protein expression of PTEN??p-ERK1/2??p-MEK1/2 and inhibited the phosphorylated of Akt, p70S6K and mTOR in HeLa cells. After pretreatment with 3-methyladenine (5 mmol??L^-1), the antiproliferative and induced-autophagy effects of celastrol were reversed. Furthermore, celastrol inhibited tumor growth and the protein expression of p-Akt and p-mTOR, but up-regulated the protein expression of LC3 ?? and Beclin 1 in vivo. CONCLUSION Antitumor effect of celastrol dependent on cells autophagy in HeLa cells via inhibition of Akt/mTOR signaling pathway in vitro and in vivo.     

6-�л�-3-����-7H-����[3,2-b]-1,2,4-���-7-ͪ�໯����ĺϳɼ�������������ø���ƻ���

??OBJECTIVE To explore the synthesis and acetylcholinesterase inhibitory activity of 6-benzyl-3-aryl-7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives. METHODS Benzaldehyde and acetylglycine were used as raw materials and underwent Erlenmeyer-Pl??chl reaction, condensation reaction, hydrolysis reaction, condensation reaction to obtain 6-benzyl-3-thioxo-3,4-dihydro-1,2,4-triazin-5(2H)-ones derivatives. The derivatives reacted with substituted ??-phenacyl chlorides to generate 6-benzyl-3-(hydroxylaryl)-7H-thiazolo[3,2-b]-1,2,4-triazin-7-ones derivatives. Then, Williamson reaction was used to yield 6-benzyl-3-aryl-7H-thiazolo[3,2-b]-1,2,4-triazin-7-ones as target compounds. RESULTS Nine 6-benzyl-3-aryl-7H-thiazolo[3,2-b]-1,2,4-triazin-7-ones were prepared as target compounds. All target compounds exhibited inhibitory activities against human AChE in vitro, five of which had inhibitory rates above 50% at 10 ??mol??L^-1. CONCLUSION Based on the screening results of AChE inhibitory activity in vitro and docking studies, there are some interactions between 6-benzyl-3-aryl-7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives and the anionic binding site and PAS zones of AChE, and the target compounds have exhibited AChE inhibitory activities.     

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??OBJECTIVE To observe the effects of hypericin on proliferation, apoptosis of leukemia cells and its possible mechanism. METHODS Subcellular localization of hypericin in leukemia cells by fluorescence microscopy. MTT(3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) test was adopted to observe the inhibitory effects of hypericin on the proliferation of leukemia cells and calculated its half maximal inhibitory concentration(IC₅₀). The technology of flow cytometry, Annexin-V-FITC/PI double stained method were employed to measure the cell apoptosis of leukemia cells after hypericin treatment. RESULTS The optimal time for hypericin to entry into cells was 16 h. Hypericin could inhibit the proliferation of leukemia cells in vitro, and the inhibition presented obvious dose-effect relationship(r=0.990 5, P??0.01). The apoptotic ratio of leukemia cells was gradually increased. The ratio of Bax/Bcl-2 was significantly increased, and the apoptotic protein caspase-3, 8, 9 is cleaved and activated. CONCLUSION Hypericin could inhibit the growth of leukemia cells, induce the apoptosis through induction of caspase dependent apoptosis pathway.     

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??OBJECTIVE To synthesize cationic polymers of arginine-histidine (HRss) based on disulfide crosslink and construct novel nano-complex HRss/miR-15-a, then study its anti-prostate cancer effect in vitro. METHODS ¹H-NMR was used to characterize HRss2/miR-15-a. Zeta sizer was adopted to estimate the Zeta potential and particle size of the nano-complex. Gel electrophoresis was employed to determine the condensation capacity of HRssto miR-15-a. The cytotoxicity and transfection efficiency of HRss was evaluated using prostate cancer stem-like cells (RC-92a/hTERT). Transwell chambers were used to evaluate the influence of HRss/miR-15-a against the motility of RC-92a/hTERT. RESULTS The RESULTS of cytotoxicity tests indicated that the carrier HRss2 had low toxicity in both normal cells and cancer cells, and the miR-15-a could be loaded in HRss2 to form stable nano-complex. The transfection efficiency and inhibited motility of HRss2/miR-15-a against RC-92a/hTERT were statistically higher than those of HRss1/miR-15-a and HRss3/miR-15-a. CONCLUSION HRss may be useful for gene delivery, and HRss2, as the optimum polycationic carrier as shown by in vitro evaluation, has the potential to become a novel gene vector in the therapy of prostate cancer.