AIMThree major enzymes of HIV-1, reverse transcriptase (RT), protease (PR), and integrase (IN), are important targets for anti-HIV drugs. Nine RT and five PR inhibitors have been effectively used in treatment of AIDS patients. In order to find active integrase inhibitors, twenty polyhydroxylated aromatic compounds were tested.

METHODSELISA method was used to test the integrase activity. The synthesized donor substrate oligonucleotide representing the HIV-1 U5LTR was immobilized onto Covalink polystyrene microtiter plates, and a synthesized biotinlated 20 bp oligonucleotide was used as the target substrate. The products were detected and quantified by a colorimetric avidin-linked alkaline phosphatase reporter system.

RESULTSCompound NQ-2 was found to inhibit HIV-1 integrase with the IC50 of 78.5 mumol.L-1 by ELISA method. Its novel analogue NQ-3 was found to be 2 fold more potent on HIV intrgrase than NQ-2, IC50 was 37.2 mumol.L-1. The IC50s of NQ-2 and NQ-3 to inhibit the 3'-pro + assembly activity of integrase were 96.94 mumol.L-1 and 8.48 mumol.L-1; to inhibit assembly activity were 168 and 6.9 mumol.L-1 and to inhibit strand-transfer activity were 49.8 and 1.1 mumol.L-1, respectively. Compound NQ-2 mostly inhibited the strand transfer activity of HIV-1 integrase. Compound NQ-3 inhibited both the assembly and strand-transfer with high activities.

CONCLUSIONNaphthoquinone compound NQ-3 was found to be a novel HIV integrase inhibitor which warrants further study. Uncoupled ELISA HIV integrase assay is shown to be useful to screen HIV-1 integrase inhibitors.

Coumarins ; pharmacology ; HIV Integrase ; drug effects ; metabolism ; HIV Integrase Inhibitors ; pharmacology ; HIV-1 ; drug effects ; enzymology ; Inhibitory Concentration 50 ; Naphthoquinones ; pharmacology ; Polycyclic Aromatic Hydrocarbons ; pharmacology ; Stilbenes ; pharmacology

OBJECTIVETo find a research method suitable to multi-component multi-index composition-activity relationship of traditional Chinese medicines (TCMs) with the antioxidant activity of four compatible active constituents of TCMs as the subject.

METHODLARS-based regression algorithm and comprehensive weight coefficient method were adopted to study in vitro clearance of DPPH and polyaromatic hydrocarbon with different doses of four compatible active constituents--total flavonoids of Glycyrrhizae Radix et Rhizoma (TFG), Ginkgo Folium extract (GBE), total flavonoids of Epimedii Folium (TFE) and astragaloside (AST) according to the comprehensive efficacy assessment procedures, that is test design, efficacy test and mathematical modeling (model verification).

RESULTLARS and comprehensive weight coefficient method was adopted to assess the optimal comprehensive efficacy of clearing DPPH and polyaromatic hydrocarbon. The results showed that the optimal dose combination of compatible constituents is TFG-GBE-TFE-AST 1: 0.2545: 0.007 6:0.011 5.

CONCLUSIONThe above compatibility of TCMs constituents can effectively clear polyaromatic hydrocarbon and DPPH with a good antioxidation. The uniform design adopted in this experiment, in combination of synthetic weight method, is suitable to the data analysis of "non-linear and small-sample" biotic experiment and the study on screening and assessment of compatibility of TCMs constituents.

Antioxidants ; chemistry ; pharmacology ; Biphenyl Compounds ; chemistry ; Chemistry, Pharmaceutical ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Medicine, Chinese Traditional ; methods ; Picrates ; chemistry ; Polycyclic Aromatic Hydrocarbons ; chemistry ; Regression Analysis

Epidemiologic studies have suggested the association between environmental exposure to volatile organic compounds (VOCs) and polycyclic aromatic hydrocarbons (PAHs) and the increased risk of incurring asthma. Yet there is little data regarding the relationship between personal exposure to air pollution and the incidence of asthma in children. This study was designed to evaluate the effect of exposure to air pollution on children with asthma by using exposure biomarkers. We assessed the exposure level to VOCs by measuring urinary concentrations of hippuric acid and muconic acid, and PAHs by 1-OH pyrene and 2-naphthol in 30 children with asthma and 30 children without asthma (control). The mean level of hippuric acid was 0.158+/-0.169micromol/mol creatinine in the asthma group and 0.148+/-0.249micromol/mol creatinine in the control group, with no statistical significance noted (p=0.30). The mean concentration of muconic acid was higher in the asthma group than in the control group (7.630+/-8.915micromol/mol creatinine vs. 3.390+/-4.526micromol/mol creatinine p=0.01). The mean level of urinary 1-OHP was higher in the asthma group (0.430+/-0.343micromol/mol creatinine) than the control group (0.239+/-0.175micromol/mol creatinine), which was statistically significant (p=0.03). There was no difference in the mean concentration of 2-NAP between the two groups (9.864+/-10.037micromol/mol in the asthma group vs. 9.157+/-9.640micromol/mol in the control group, p=0.96). In conclusion, this study suggests that VOCs and PAHs have some role in asthma.
Air Pollutants/*pharmacology ; Asthma/*physiopathology/urine ; Case-Control Studies ; Child, Preschool ; Creatinine/urine ; Female ; Hippurates/urine ; Humans ; Male ; Naphthols/urine ; Organic Chemicals/chemistry/*pharmacology ; Polycyclic Hydrocarbons, Aromatic/*pharmacology ; Pyrenes/metabolism ; Sorbic Acid/*analogs & derivatives/metabolism ; Volatilization

Objective: To evaluate the effects of polycyclic aromatic hydrocarbons (PAHs) and high risk human papillomavirus (HR-HPV) infection and their interaction on the progression of cervical intraepithelial neoplasia. Methods: A total of 486 patients, including 208 women with normal cervix (NC), 154 patients with low-grade cervical intraepithelial neoplasm (CINⅠ), 124 patients with high-grade cervical intraepithelial neoplasm (CINⅡ/Ⅲ), were selected from the cervical lesions cohort from June to December, 2014. HR-HPV was detected by using flow-through hybridization technology and the urine concentration of 1-hydroxypyrene (1-OHP) was detected with high performance liquid chromatography. By using software SPSS 22.0, the χ(2) test, trend χ(2) test, Kruskal-Wallis H test, Nemenyi rank test and Spearman rank correlation analysis were performed. And the interaction effects were evaluated by additive model. Results: The HR-HPV infection rates in NC, CINⅠ and CINⅡ/Ⅲ groups were 27.9%, 37.0% and 58.9%, respectively. The urine concentrations of 1-OHP (μmol/molCr) were 0.07±0.09, 0.11±0.10 and 0.17±0.15, respectively. With increasing severity of the cervical lesions, the HR-HPV infection rate gradually increased (trend χ(2)=29.89, P<0.001) and the high exposure rate of PAHs gradually increased (trend χ(2)=27.94, P<0.001). HR-HPV infection was positively correlated with 1-OHP exposure (r=0.680, P<0.001). There was a positive additive interaction between HPV infection and PAHs exposure in CIN Ⅱ/Ⅲ group, but it was not found in CIN Ⅰ group. Conclusion: Both HR-HPV infection and high exposure of PAHs might increase the risk of cervical intraepithelial neoplasm, and might have a synergistic effect on the progression of high-grade cervical intraepithelial neoplasia.
Case-Control Studies ; Cohort Studies ; Disease Progression ; Female ; Humans ; Papillomaviridae/isolation & purification* ; Papillomavirus Infections/virology* ; Polycyclic Aromatic Hydrocarbons/pharmacology* ; Pyrenes/urine* ; Severity of Illness Index ; Uterine Cervical Dysplasia/virology* ; Uterine Cervical Neoplasms/virology*