ABSTRACT
Thiochromanones and 1,3,4-thiadazoles as heterocyclic compounds have broad biological activities. In order to find novel compounds with antifungal activity, we synthesized a novel series of (E)-3-(((1,3,4-thiadiazol-2-yl) amino)methylene)-thiochroman-4-ones. Structures of these compounds were established by HR-MS, 1H NMR, 13C NMR and 1D-noesy. All of the synthesized compounds were screened for antifungal activity by using an established agar double dilution method (plate method) against ten fungi species in vitro. Compound 5j showed significant inhibitory activity to Colletotrichum capsici, Rhizoctonia cerealis and Aspergillus niger compared with that of the positive control carbendazim. Compounds 5h exhibited better antifungal activity to Canidia albicans and Aspergillus funigatus than the positive control fluconazole, in which the minimum inhibition concentration can reach 8 μg·mL-1 and 16 μg·mL-1. Moreover, the molecular docking method was used to study the interaction mode of compound 5h and CYP51, and the results will be helpful for designing of CYP51 inhibitors in the future.
ABSTRACT
Thiochromanones and 1,3,4-thiadazoles as heterocyclic compounds have broad biological activities. In order to find novel compounds with antifungal bioactivity, substituted thiophenol and maleic anhydride were used to synthesize the intermediate 4-oxothiochromane-2-carboxylic acid. It was reacted with 2-amino-1,3,4-thiadiazol to get fourteen target compounds containing 1,3,4-thiadazole moiety. The structures of the obtained compounds were confirmed by 1H NMR, 13C NMR and HR-MS. All compounds were investigated for antifungal activity via microdilution broth method. The results showed that the target compounds 3a and 3c to Epidermophyton floccosum and Mucor racemosus exhibited better antifungal activity than the positive control fluconazole, in which the minimum inhibition concentration can reach 8 μg·mL-1 and 16 μg·mL-1. Compound 3e showed significant inhibitory activity to Helminthosporium maydis, Sclerotinia sclerotiorum and Botrytis cinerea compared with that of the positive control carbendazim. Compound 3b exhibited inhibitory activity to Helminthosporium maydis better than the positive control carbendazim.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the inhibitory effect of lactic acid on semen-derived amyloid (SEVI) fibril formation.</p><p><b>METHODS</b>PAP248-286 (2 mg/mL) was incubated with 4.0, 2.0, 1.0, 0.5, 0.25, and 0.125 mg/mL of lactic acid. After incubation for different times, aliquots were drawn from each sample for Thioflavin T (ThT) and Congo red staining to monitor semen-derived amyloid fibril formation. The β sheet structure formation of PAP248-286 was measured by circular dichroism spectrum, and the morphology of amyloid fibrils incubated with or without lactic acid was observed with transmission electron microscopy (TEM). The enhancing effect of amyloid fibril incubated with lactic acid at different time points was determined using virus infection assay. PAP248-286 (2 mg/mL) was incubated with dilutions of vaginal secretion from healthy women, and amyloid fibril formation was detected with ThT and Congo red staining.</p><p><b>RESULTS</b>Lactic acid inhibited SEVI fibril formation in a dose-dependent manner in vitro. Lactic acid at 0.5 mg/mL completely inhibited 2 mg/mL SEVI fibril formation within 48 h. After incubation for 48 h, lactic acid at 1 mg/mL inhibited the formation of β-sheet structure of SEVI (2 mg/mL) and completely inhibited 2 mg/mL PAP248-286 aggregation as observed with TEM. In the presence of lactic acid, PAP248-286 lost the ability to enhance virus infection. Vaginal secretion inhibited SEVI fibril formation in a dose-dependent manner, and virtually no SEVI fibril occurred after incubation of 2 mg/mL PAP248-286 with 67% vaginal secretion.</p><p><b>CONCLUSION</b>Lactic acid inhibits SEVI fibril formation in vitro.</p>
ABSTRACT
In order to develop potent antidiabetic agents that have inhibitory effect to α-glucosidase, twelve β-acetamido ketone derivatives such as N-{[(substituted-4-oxo-thiochroman-3-yl)phenyl]-methyl}acetamide are designed and synthesized through one-pot Dakin-West reaction. Their chemical structures are confirmed by 1H NMR, 13C NMR, IR and HR-MS. In vitro α-glucosidase inhibition assays of compounds 4a-4l were carried out using glucose oxidase method. The result indicated that most of them possess inhibitory activity in vitro. Compound 4k showed the most potent inhibitory activity with 87.3% inhibition of α-glucosidase at the concentration of 5.39 mmol·L-1. The structure-activity relationship of these β-acetamido ketone derivatives was discussed preliminarily. Moreover, the molecular docking method was used to study the interaction mode of compound 4k and α-glucosidase. Our results will be helpful for designing of α-glucosidase inhibitors in the future.
ABSTRACT
In order to develop potent antidiabetic agents that have inhibitory effect to a-glucosidase, twelve β-acetamido ketone derivatives such as N-{[(substituted-4-oxo-thiochroman-3-yl)phenyl]-methyl}acetamide are designed and synthesized through one-pot Dakin-West reaction. Their chemical structures are confirmed by 1H NMR, 13C NMR, IR and HR-MS. In vitro α-glucosidase inhibition assays of compounds 4a-41 were carried out using glucose oxidase method. The result indicated that most of them possess inhibitory activity in vitro. Compound 4k showed the most potent inhibitory activity with 87.3% inhibition of α-glucosidase at the concentration of 5.39 mmol x L(-1). The structure-activity relationship of these β-acetamido ketone derivatives was discussed preliminarily. Moreover, the molecular docking method was used to study the interaction mode of compound 4k and α-glucosidase. Our results will be helpful for designing of α-glucosidase inhibitors in the future.
Subject(s)
Acetamides , Glycoside Hydrolase Inhibitors , Pharmacology , Hypoglycemic Agents , Pharmacology , Molecular Docking Simulation , Structure-Activity Relationship , alpha-Glucosidases , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To explore the efficacy of frozen-thawed embryo transfer combined with intrauterine administration of autologous peripheral blood mononuclear cells (PBMCs) in the treatment of repeated implantation failure (RIF).</p><p><b>METHODS</b>PBMCs obtained from 3 patients with RIF on the day of follicle rupture (natural cycle) or when the endometrial thickness reached 8 mm (hormone replacement cycle) were cultured in the presence of HCG for 48 h. The cultured PBMCs, along with freshly isolated PBMCs, were administered into the uterine cavity of the patients. Vitrified cleavage-stage embryos or blastocysts transfer was performed on day 3 or 5, respectively.</p><p><b>RESULTS</b>Vitrified embryo or blastocyst transfer resulted in pregnancy and healthy live births in all the 3 patients.</p><p><b>CONCLUSION</b>Frozen-thawed embryo transfer combined with intrauterine administration of autologous PBMCs may be an effective and safe approach to the treatment of RIF and may improve the outcomes of assisted reproduction.</p>
Subject(s)
Adult , Female , Humans , Pregnancy , Blastocyst , Cryopreservation , Embryo Implantation , Embryo Transfer , Methods , Fertilization in Vitro , Methods , Monocytes , Pregnancy Rate , Treatment FailureABSTRACT
<p><b>OBJECTIVE</b>To explore the relationship between protein oxidation levels in the follicular fluid and the outcome parameters of in vitro fertilization-embryo transplantation (IVF-ET).</p><p><b>METHODS</b>The levels of advanced oxidation protein products (AOPP) in the follicular fluid were measured in 64 women with tubal infertility undergoing IVF-ET. The relationship between the AOPP levels and IVF-ET outcome parameters was analyzed.</p><p><b>RESULTS</b>AOPP levels showed significant inverse correlations between the proportion of mature oocytes (r=-0.401, P=0.001), fertilization rate (r=-0.257, P=0.045), cleavage rate (r=-0.290, P=0.024) and good embryo rate (r=-0.520, P=0.000). AOPP levels differed significantly between the groups with different retrieved oocyte numbers (F=3.851, P=0.027), being the lowest in women with 8 to 15 retrieved oocytes and the highest in those with retrieved oocytes below 8. The AOPP level in the non-pregnant women was significantly higher than that in the pregnant women (t=3.665, P=0.001). The AOPP levels also differed significantly with age (F=15.919, P=0.000), and the women >35 years of age had the highest level and those below 30 years had the lowest level.</p><p><b>CONCLUSION</b>Protein oxidative stress is present in the follicular fluid of women on IVF-ET cycles. High level of AOPP may have adverse effects on the oocytes and early embryonic development and may affect the outcome of IVF-ET.</p>
Subject(s)
Adult , Female , Humans , Pregnancy , Embryo Transfer , Fertilization in Vitro , Follicular Fluid , Metabolism , Infertility, Female , Metabolism , Therapeutics , Oxidation-Reduction , Oxidative Stress , Pregnancy Rate , Proteins , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To understand the current situations of saturnism and blood lead levels of children resided in village and circumjacent areas, and to know its relations with sex, age and other factors on children' s health as to providing some evidences for prevention and control.</p><p><b>METHODS</b>An epidemiological survey was conducted for finding out the pollution sources and for a better understanding of the surrounding environment. All 221 children under 14 years old, from the lead pollution villages and surrounding establishments were enrolled, and their blood lead levels were detected by graphite atomizer absorption spectrophotometer method. Symptoms of the saturnism were investigated through a standardized questionnaire. SPSS13.0 software was administrated for data analysis.</p><p><b>RESULTS</b>High blood lead level identification rate was 66.06% (146/221), and saturnism rate 32.13% (71/221). The children's blood lead levels among group 1, group 2, group 3 in this village and jade factory were (161.20 +/- 32.94), (176.60 +/- 43.62), (258.00 +/-106.08) and (238.01 +/- 55.20) microg/L respectively and the significant differences were observed through Kruskal-Wallis test (chi2 = 51.84, df= 3, P<0. 01). The blood lead levels of children from group 3 in this village and the jade factory were higher than those of other two groups. No correlation was found between children's age and blood lead level (r = 0.10, P = 0.13). There was a significant difference in blood lead levels between boys and girls (t' = 3.83, P<0.01). With the children's blood lead levels rising, the occurrence rate of main saturnism symptoms was significantly increased. This survey suggested that the pollution source was a coarse lead smelter.</p><p><b>CONCLUSION</b>The blood lead level should ke overwhelmingly increased among children who live nearby the higher level of lead blood, that living nearby the lead smeltery,might result in stautnism and negative effect on children's healthy.</p>
Subject(s)
Child , Female , Humans , Male , Environmental Pollution , Industrial Waste , Lead , Blood , Lead Poisoning , Epidemiology , MetallurgyABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of two different doses of letrozole in promoting ovulation in infertile women with polycystic ovarian syndrome (PCOS).</p><p><b>METHODS</b>Seventy-six PCOS infertile women undergoing intrauterine insemination (IUI) or with anovulation were divided into two groups and received oral letrozole at the daily dose of 2.5 (n=36) or 5.0 mg (n=40) from the 3rd to the 7th day of the menstrual cycle. Three days after discontinuation of the medication (the 10th day of the menstrual cycle ), ultrasound scanning was performed to monitor the follicle development. When the diameter of the biggest follicle reached 14 mm, the presence of luteinizing hormone (LH) was monitored; when LH positivity was detected, blood samples were drawn to test follicle-stimulating hormone (FSH), LH, estradiol (E2) and testosterone (T) levels. Human chorionic gonadotropin (hCG, 10 000 U) was then injected to induce ovulation.</p><p><b>RESULTS</b>The ovulation rate, stimulation follicle days, diameter of the biggest follicle on the day of LH positivity and the thickness of endometrium were all similar between the two groups (P>0.05). But in women receiving 5.0 mg letrozole, both the number of mature follicles and pregnancy rate were significantly higher than those in women having the half dose (P<0.05). The levels of FSH, LH, E2, and T on the third day of menstruation and on the day of HCG injection were similar between the two groups (P<0.05).</p><p><b>CONCLUSION</b>Letrozole at the dose of 5.0 mg/day produces higher pregnancy rate and more mature follicles in fertile women with PCOS.</p>
Subject(s)
Adult , Female , Humans , Aromatase Inhibitors , Fertility Agents, Female , Infertility, Female , Drug Therapy , Insemination, Artificial , Nitriles , Ovulation Induction , Methods , Polycystic Ovary Syndrome , TriazolesABSTRACT
<p><b>OBJECTIVE</b>To evaluate the efficacy of ovulation stimulation protocol with gradual increment of gonadotropin in women with high ovarian response.</p><p><b>METHODS</b>A retrospective study was conducted between june 2005 and April 2006 in 70 women undergoing controlled ovarian hyperstimulation. The clinical outcomes of the women using gradual increment protocol were compared with those of women receiving other ovulation-stimulating protocols.</p><p><b>RESULTS</b>The mean number of large follicles (>or=14 mm) and retrieved oocytes on the day of retrival was significantly lower, but the duration of stimulation was significantly longer in the gradual increment group than in the control group. The rate of follicular puncture was also higher in the former group. The clinical pregnancy rate, total gonadotropin dosage, cancellation rate and incidence of ovarian hyperstimulation syndrome were similar for the two groups.</p><p><b>CONCLUSION</b>Ovulation stimulation protocol with gradually increased gonadotropin may provide a promising alternative for controlled ovarian hyperstimulation in women with a strong ovarian response.</p>
Subject(s)
Adult , Female , Humans , Embryo Transfer , Fertilization in Vitro , Gonadotropins, Pituitary , Ovarian Hyperstimulation Syndrome , Ovulation Induction , Methods , Retrospective StudiesABSTRACT
<p><b>OBJECTIVE</b>To observe the fetus protection effects of Zhixue Baotai Decoction (ZBD) on women of early threatened abortion with dark area surrounding pregnancy sac.</p><p><b>METHODS</b>The 105 patients with early threatened abortion, in whom vaginal bleeding was shown already, were randomly assigned to the treatment group and the control group, who were treated respectively with ZBD and progesterone to protect fetus. The efficacy of treatment was evaluated by dynamic monitoring of serum hormone and B-ultrasonic examination.</p><p><b>RESULTS</b>Among the 54 cases in the treatment group the fetus was protected successfully, showing a fetus protecting rate of 81.5%; while among the 51 cases in the control group, the protection was effective in 22 cases (43.1%), the success rate in the former was better (P<0.01). The dark area was absorbed in 16 out of 19 cases (84.2%) in the treatment group, while in the control group absorption occurred only in 6 out of 17 (35.3%).</p><p><b>CONCLUSION</b>The effect of ZBD is superior to that of progesterone in treating women of early threatened abortion with dark area surrounding pregnancy sac.</p>