To discover novel fluoroquinolone lead compounds as possible anti-infective or/and antitumor chemotherapies, combination principle of pharmacophore-based drug design, a series of novel tricyclic fluoroquinolone title compounds, [1,2,4]triazino[3,4-h][1,8]naphthyridine-8-one-7-carboxylic acid derivatives ( 5a-5p), were designed and synthesized with a fused [1,2,4]-triazine ring unit. Their structures were characterized by spectral data and elemental analysis and the in vitro antibacterial and anti-cell proliferation activities were also evaluated. The results showed that the titled compounds exhibited more significant inhibitory activities against drug-resistant bacteria (Methicillin-resistant Staphylococcus aureus and multi drug-resistant Escherichia coli strains) and three tested cancer cell lines (human hepatoma SMMC-7721, murine leukemia L1210 and human murine leukemia HL60 cells). Interestingly, SAR showed that compounds with electron-donating groups attached to benzene ring had stronger antibacterial activity than antitumor activity, but electron-withdrawing compounds displayed more potential antitumor activity than antibacterial activity, especially antitumor activity of nitro compounds was comparable to comparison doxorubicin. Thus, novel triazine-fused tricyclic fluoroquinolones as potent anti-infective or/and antitumor lead compounds are valuable to pay attention and for further development.
Animals ; Anti-Bacterial Agents ; chemical synthesis ; chemistry ; Antineoplastic Agents ; chemical synthesis ; chemistry ; Carboxylic Acids ; Carcinoma, Hepatocellular ; Cell Line ; Cell Proliferation ; Drug Design ; Escherichia coli ; drug effects ; Fluoroquinolones ; chemical synthesis ; chemistry ; HL-60 Cells ; Humans ; Leukemia L1210 ; Liver Neoplasms ; Methicillin-Resistant Staphylococcus aureus ; drug effects ; Mice ; Naphthyridines ; Triazines

To explore an efficient strategy for the conversion of antibacterial fluoroquinolones into antitumor fluoroquinolones, an azole heterocyclic ring of oxadiazole instead of the C-3 carboxylic acid group with a functionalized hydrazone group as a modified side-chain, fifteen novel 2-(fluoroquinolon-3-yl)-oxadiazole-5- sulfanylacetylhydrazone derivatives 7a-7o were designed and synthesized on the basis of the pharmacophore hybridization principle from pefloxacin, separately. The structures for fifteen title compounds were characterized by elemental analysis, 1H NMR and MS, and their in vitro antitumor activity against Hep-3B cell line was evaluated by a MTT assay. The results showed that the title compounds exhibited more significantly inhibitory activity than that of the parent pefloxacin, in which compounds with electron-withdrawing group attached on aryl ring had more potency than that of compounds with electron donating group, especially compounds with a carboxylic substituent were comparable to comparison doxorubicin. It suggests that it is favorable for an improvement of antitumor activity to remain a carboxylic acid unit at the aromatic ring.
Antineoplastic Agents ; chemical synthesis ; chemistry ; Cell Line, Tumor ; Fluoroquinolones ; chemistry ; Humans ; Oxadiazoles ; chemistry ; Structure-Activity Relationship

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Carbon-nitrogen lyases (E.C.4.3) are a group of enzymes that release ammonia, amidine or amino group etc, and also show ability to form double bond or ring structure. Specifically, enzymes forming amino group are called amine-lyases (E.C.4.3.3), which are critical in the industrial production of many medicine intermediates. In this review is a summary of four major amine-lyases in terms of their source, enzymatic characteristics and their applications in preparation of pharmaceutical intermediates.

Bioprocess equipment is of great importance in application of modern industrial biotechnology.With the rapid development of industrial biotechnology,demands for talents capable of understanding the theory,design and manipulation of modern bioprocess equipment increased.The experiences in aspects such as the building of teachers' contingent,construction of teaching materials,innovation of teaching method from the top-quality course construction of Bioprocess Equipment was discussed in this paper.

Tautomycin is one of well-known specific protein phosphatase inhibitors and exhibiting potent antifungal ability, especially to Sclerotinia sclerotiolum. This article reviews the recent research progress of tautomycin, focusing on its inhibition region and biosynthesis.

Objective To investigate the hypoglycemic effects of Laminaria japonica (L. japonica) on diabetic model induced by alloxan in rats. Methods Sixty healthy female rats were used to establish diabetic models by injecting alloxan peritoneally, and L.japonica was applied as raw materials for potential marine drugs.The levels of fasting blood glucose (FBG) were detected by automatic blood glucose device. Enzyme linkedimmunoabsorbant assay was applied to determine the insulin level in serum. The shape and structure of isletcells were observed with histopathological staining, and the expression of superoxide dismutase (SOD) and inducible nitric oxide synthase (iNOS) in islet cells were detected by immunohistochemical technique. Results After the treatment, the levels of FBG of L.japonica treated group B [(9.37±1.70) mmol/LandC (9.18±1.65 ) mmol/L, F= 32.81, q=6.35～11.72, P<0.05 ] reduced, while the serum levels of insulin in treated group A, Band C (0.0378±0.0026, 0.0378±0.0027, 0.0367±0.0035) increased(F= 11.40, q=4.28～8.47, P<0.05) significantly than those of diabetic model group (0.0456 ±0.0057) . The shape and structure of islet cells improved with the up-expressing SOD(t=4.73～4.76, P<0.05)and down-expressing iNOS (t=4.81～5.30, P<0.05) in L.japonica treated group B and C than those in diabetic model group. Conclusion L.japonica might decrease the serum level of FBG through promoting the islet cell recovery by an anti-oxide effect.

Objective To examine the expressions of glyoxalase Ⅰ (GLO-Ⅰ ) in endometrial cancer tissues and cell lines and to investigate the roles of GLO-Ⅰ on proliferation and apoptosis in endometrial cancer cells. Methods Immunohistochemistry, western blot and RT-PCR were used to investigate the expressions of GLO-Ⅰ protein and mRNA in endometrial cancer tissues and Ishikawa cell lines ;enzyme activity of GLO-Ⅰ in normal endometrium, endometrial cancer and paraneoplastic tissue samples was detected with spectrophotometer; proliferation and apoptosis of Ishikawa cell before and after RNA interference (RNAi) procedure were detected by the methyl thiazolyl tetrazolium (MTT) and flow cytometry, respectively. Results (1)There were significant differences of GLO-Ⅰ expression between normal endometrium (0/19) and endometrial cancer tissues ( 76%, 22/29 ); these were also significant differences of enzyme activity of GLO-Ⅰ among normal endometrium, paraneoplastic and endometrial cancer tissues( 1.1,0.8 vs 92.3 IU/mg; P <0.01 ). Enzyme activity of GLO-Ⅰ in fresh normal endometrium and paraneoplastic tissues was weak, while that of fresh endometrial cancer tissues was as high as 92. 3 IU/mg in average. (2)The expression of GLO-Ⅰ mRNA in Ishikawa cell transfected with GLO-Ⅰ siRNA was significantly lower than that in negative group (0.25 ± 0.06 vs 0.93 ± 0.10, P < 0.0l ), and the similar results that in the expression of GLO-Ⅰ protein (0.38 ±0.06 vs 0.94 ±0.13, P <0.01 ). (3) Proliferation in Ishikawa cell was significantly inhibited after silencing RNA expression of GLO-Ⅰ ( P = 0.028 ). The apoptosis rate of cells transfected with GLO- Ⅰ siRNA was significantly higher than that of negative control group and blank control group [ ( 6.7 ± 0.8 ) % vs ( 1.2 ± 0.4) %, ( 1.4 ± 0.4 ) %; P < 0.01 ]. Conclusion The expression and enzyme activity of GLO- Ⅰ is significantly increased in endometrial cancer, which could promote abnormal proliferation and inhibit apoptosis in endometrial cancer cells.

Objective To investigate the expression and distribution of the downstream substrate of extracellular regulated protein kinase(ERK1/2) pathway, ternary complex factor phospho-Elk-1, in rat brains with chronic fluorosis, and reveal the mechanism of the impaired learning and memory ability caused by chronic fluorosis. Methods Seventy-two SD rats, weighing 100 - 120 g, were randomly divided into 3 groups, 24 in each group (half male and half female). The rats in control group were fed with tap water (fluoride < 0.5 mg/L); low- and high-dose fluoride groups were fed with tap water with different concentrations of NaF(5.0,50.0 mg/L F-, respectively). After 6 months, body weight was weighed, dental fluorosis was determined by observation and urinary fluoride and bone fluoride were detected by fluorine ion-selective electrode; the learning ability of rats was measured by navigation test of Morris water maze, and memory ability by spatial probe test in Morris water maze; the expression and distribution of phospho-Elk-1 in different brain regions were detected by immunohistochemistry method. Results In low- and high-fluoride groups, the body weight of rat[(449.2 ± 77.1), (312.8 ± 89.7)g] was significantly decreased than that of control [(635.5 ± 76.2 )g, all P< 0.05], the varying degrees of dental fluorosis were observed(x2 = 7.83, P<0.05), urinary fluoride[(2.56 ±0.91),(5.73 ±3.14)mg/L] and bone fluoride[(709.2 ± 37.4) ,(1306.3 ± 102.4) mg/kg] were significantly higher than those in controls[(0.92 ± 0.30)mg/L,(348.5 ± 89.2)mg/kg, all P< 0.05]. The escape latency of low- and high-fluoride groups[ (7.4 ± 4.1), (12.2 ± 5.7)s] was longer than that of control [(4.8 ± 2.7 )s, all P < 0.05] and the escape latency in high-fluoride group was significantly longer than that in other groups (all P < 0.05); in spatial probe test, the time of first crossing platform was longer in rats with fluorosis [(4.18 ± 1.10),(5.89 ± 0.56)s] as compared to control[(1.17 ± 0.75)s, all P< 0.05]. Expressions of phospho-Elk-1 in the hippocampus CA1(167.4 ± 8.3,163.2 ± 9.4), CA2(175.7 ± 5.0,183.3 ± 4.2), CA3(165.2 ± 11.6,162.9 ± 4.4), CA4(168.7± 6.9,169.5 ±5.3), fascia dentate (185.2 ±4.0,193.1 ±6.1) and caudate putamen( 181.4 ± 3.8, 179.8 ± 5.5) in low- and high-fluoride groups were higher than those of controls(142.4 ± 8.1,144.9 ± 8.4,143.6 ± 5.8, 116.8 ± 9.1,140.2 ± 7.8,163.1 ± 13.1, all P< 0.05). Conclusion Chronic fluorosis can cause increased expression of phospho-Elk-1 in the hippocampus and caudate putamen region of rat brains, which might be related to the mechanisms of decreased learning and memory ability of rats overexposed to fluoride.

Objective To analyze the ultrasonic features of thyroid microcarcinoma (TMC) and the causes of misdiagnosis. Methods The ultrasonic features including shape, margin, echogenecity, microcalcification, vascularity and lymphadenopathy were analyzed retrospectively in 26 pathologically-proven TMC patients. Results In 26 cases, 11 cases were diagnosed correctly before operation (11/26, 42.31%), 12 cases were misdiagnosed (12/26, 46.15%) as adenoma or benign nodule, and 3 cases were missed diagnosed (3/26, 11.54%). Among the 23 cases detected on ultrasound, 21 cases were solid and hypoechoic (21/23, 91.30%);19 cases were ill-defined (19/23, 82.61%);12 cases were taller than wide in shape (12/23, 52.17%); 14 cases had microcalcification (14/23, 60.87%); 7 cases showed central or peripheral blood flow signals (7/23,30.43%) with arterial resistance index>0.70 in 3 lesions and<0.70 in 4 lesions. Conclusions Several ultrasonographic features are helpful in identiifcation of TMC, including hypo/iso-echogenecity, ill-deifned margin, taller-than-wide shape, microcalciifcation, arterial signals with high resistance index, and abnormal lymphadenopathy. Moreover, for cases with multiple lesions, to the potential co-existence of benign and malignant lesions should be considered.