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1.
α-Glucosidase is a catabolic enzyme that regulates the body’s plasma glucose levels by providing energy sources to maintain healthy functioning. 2-Amino-thiadiazole (1–13) and 2-amino-thiadiazole based Schiff bases (14–22) were synthesized, characterized by 1H NMR and HREI-MS and screened for α-glucosidase inhibitory activity. All twenty-two (22) analogs exhibit varied degree of α-glucosidase inhibitory potential with IC50 values ranging between 2.30 ± 0.1 to 38.30 ± 0.7 μM, when compare with standard drug acarbose having IC50 value of 39.60 ± 0.70 μM. Among the series eight derivatives 1, 2, 6, 7, 14, 17, 19 and 20 showed outstanding α-glucosidase inhibitory potential with IC50 values of 3.30 ± 0.1, 5.80 ± 0.2, 2.30 ± 0.1, 2.70 ± 0.1, 2.30 ± 0.1, 5.50 ± 0.1, 4.70 ± 0.2, and 5.50 ± 0.2 μM respectively, which is many fold better than the standard drug acarbose. The remaining analogs showed good to excellent α-glucosidase inhibition. Structure activity relationship has been established for all compounds. The binding interactions of these compounds were confirmed through molecular docking. 相似文献
2.
《Bioorganic & medicinal chemistry》2014,22(1):141-147
A series of new sulfonamides was prepared starting from 2-oxo-N′-(4-sulfamoylphenyl)-propanehydrazonoyl chloride, a sulfanilamide derivative, which was reacted with aroylhydrazides, amines, or thiols. A library of derivatives incorporating aroylhydrazone, [1,2,4]triazolo[3,4-b][1,3,4]thiadiazinyl- or 2-(cyanophenyl-methylene)-1,3,4-thiadiazol-3(2H)-yl moieties was thus synthesized. The new compounds were investigated as inhibitors of four α-carbonic anhydrases (CAs, EC 4.2.1.1), the human (h) isoforms hCA I and II, and the bacterial ones recently isolated from the extremophilic bacteria Sulfurihydrogenibium yellostonense (SspCA) and Sulfurihydrogenibium azorense (SazCA). Low nanomolar activity was observed against hCA II (KIs of 0.56–17.1 nM) whereas hCA I was less inhibited by these compounds (KIs of 86.4 nM–32.8 μM). The bacterial CAs were also effectively inhibited by these derivatives (KIs in the range of 0.77–234 nM against SazCA, and of 6.2–89.1 against SspCA, respectively), with several low nanomolar/subnanomolar inhibitors detected against both of them. As SspCA and SazCA are among the most thermostable and catalytically active CAs, it is of interest to find modulators of their activity for potential biotechnologic applications. 相似文献
3.
《Bioorganic & medicinal chemistry》2014,22(22):6324-6332
The blood coagulation cascade represents an attractive target for antithrombotic drug development, and recent studies have attempted to identify oral anticoagulants with inhibitory activity for enzymes in this cascade, with particular attention focused on thrombin and factor Xa (fXa) as typical targets. We previously described the discovery of the orally active fXa inhibitor darexaban (1) and reported a unique profile that compound 1 rapidly transformed into glucuronide YM-222714 (2) after oral administration. Here, we propose a novel strategy towards the discovery of an orally active anticoagulant that is based on the bioconversion of a non-amidine inhibitor into the corresponding conjugate to boost ex vivo anticoagulant activity via an increase in hydrophilicity. Computational molecular modeling was utilized to select a template scaffold and design a substitution point to install a potential functional group for conjugation. This strategy led to the identification of the phenol-derived fXa inhibitor ASP8102 (14), which demonstrated highly potent anticoagulant activity after biotransformation into the corresponding glucuronide (16) via oral dosing. 相似文献
4.
Reza Modarres 《Biometrical journal. Biometrische Zeitschrift》1993,35(7):785-790
The likelihood ratio test for testing equality of vgE;2 correlated variables is developed. In general, evaluation of the test statistic involves the iterative optimization of a likelihood function with 1 + v(v – 1)/2 parameters. The explicit form of the test statistic is derived in the bivariate case, and an iterative algorithm for determining the maximum likelihood estimates is suggested. A limited Monte Carlo study determines the behavior of the proposed procedure under the null hypothesis and variety of parameter values. 相似文献
5.
Samarcandin 1, a natural sesquiterpene-coumarin, was isolated as well as elucidated from F. assa-foetida which has significant effect in Iranian traditional medicine because of its medicinal attitudes. The crystal structure of samarcandin was determined by single-crystal X-ray structure analysis. It is orthorhombic, with unit cell parameters a = 10.8204 (5) Å, b = 12.9894 (7) Å, c = 15.2467 (9) Å, V = 2142.9 (2) Å3, space group P212121 and four symmetry equivalent molecules in the unit cell. Samarcandin was isolated in order to study for its theoretical studies as well as its cellular toxicity as anti-cancer drug against two cancerous cells. In comparison with controls, our microscopic and MTT assay data showed that samarcandin suppresses cancer cell proliferation in a dose-dependent manner with IC50 = 11 μM and 13 for AGS and WEHI-164 cell lines, respectively. Density functional theory (DFT) and time-dependent density functional theory (TD-DFT) of the structure was computed by three functional methods and 6-311++G7 standard basis set. The optimized molecular geometry and theoretical analysis agree closely to that obtained from the single crystal X-ray crystallography. To sum up, the good correlations between experimental and theoretical studies by UV, NMR, and IR spectra were found. 相似文献
6.
《Bioorganic & medicinal chemistry》2016,24(8):1778-1785
As part of a selection strategy for artificial nucleic acids (XNA) (to be considered as potential new information systems in vivo), we have carried out a modelling study on cyclohexanyl nucleic acids (CNA) duplexes and hairpins. CNA may form a duplex as well as hairpin structures, having the carbocyclic nucleosides in the 4C1 conformation (with equatorial basis). The geometry of ds CNA is close to that of a HNA:RNA duplex. We demonstrated that CNA triphosphates function as a substrate for polymerases. Modelling experiments indicate that the monomers are probably presented to the polymerase in the 1C4 conformation. 相似文献
7.
Sotiris K. Hadjikakou Constantinos D. Antoniadis Maciej Kubicki Spyros Karkabounas 《Inorganica chimica acta》2005,358(10):2861-2866
A novel water stable, antimony(III) complex with the heterocyclic thioamide; 2-mercapto-pyrimidine (pmtH), of formula [Sb(pmt)3] · 0.5(CH3OH), has been synthesized and characterized by elemental analysis, 1H, 13C NMR and FT-IR spectroscopic techniques. Crystal structure of the molecule has been determined by X-ray diffraction at ambient conditions. The compound [C12H9N6S3Sb · 0.5(CH3OH)] is monoclinic, space group P21/c, a = 7.0646(7), b = 16.3767(14), c = 14.7265(13) Å, β = 92.016(7)°, Z = 4. In complex, three sulfur and three nitrogen atoms from thione ligands form a distorted pendagonal pyramidal geometry around antimony(III). The toxicity of the compound against tumor pleiomorphic cells, which has been isolated from a leiomyosarcoma tumor in the Wistar rat (chemical carcinogenesis using BaP) was studied in vitro. The results show that the compound did not destroy or prevent multiplication in vitro in leiomyosarcoma cells in low doses. The influence of the compound in the platelet aggregation, which correlates with the above tumor cells enhanced metastatic potential, has also been studied. The anti-metastatic capability study shows that the compound inhibited cancer cell induced aggregation up to the value of 10% in all mM concentrations tested. 相似文献
8.
Yuzuru Hamada Toshifumi Udono Migaku Teramoto Ikuo Hayasaka 《Primates; journal of primatology》1998,39(2):157-169
Skeletal developmental of chimpanzees was studied cross-sectionally. By application of the TW2 method, we described the skeletal
development of chimpanzees and compared their skeletal development with humans'. A development pattern of chimpanzees repeated
accelerations and decelerations displaying “early-juvenile trough,” “pre-adolescent peak,” “mid-adolescent trough,” and “post-adolescent
peak” in incremental curves. Sex differences in skeletal development are slower development in males during infant and early
juvenile phases, and greater increment around the adolescent phase in males. Females are fully mature at younger ages than
males, e.g. about one and a half years. In comparison with chimpanzees, humans have such characteristics as a longer slower
period of juvenile development and a shorter spurt-like adolescent fast period which ends with full maturity. 相似文献
9.
Growth form is one of the important life history traits ultimately influencing plant fitness. Potentilla palustris is a stoloniferous plant growing in a range of habitats from densely vegetated wet meadows to acidic transitional fens, and
its growth form varies according to habitat. In a four year multi-site comparative study, we investigated which biotic and
abiotic characteristics influence most its growth traits. Vegetation composition and physiognomy, as well as numerous abiotic
environmental variables, were recorded at 32 study sites located on an altitudinal gradient. Growth traits of P. palustris were best explained by the surrounding vegetation physiognomy and not by abiotic conditions, although the latter obviously
represents the factors indirectly influencing its growth. Stolon length traits and branching were positively correlated with
vegetation density and height, and negatively with altitude. Plants flowered more in taller vegetation, and leaf area was
greater in wetter sites with lower vegetation cover. Potentilla palustris appeared to be well adapted to transitional fens, but its vegetative growth was fastest in wet meadows and alluvial habitats
on highly organic humid soils. It produced more branches and larger leaves in alluvial habitats with open water, while it
had enhanced generative reproduction in wet meadows. Species composition was less important than vegetation physiognomy. In
less favorable habitat types, P. palustris prefers an escape strategy of linear growth. Internode length exhibited pronounced plasticity, increasing particularly in
tall dense vegetation of lower altitude, whereas internode number remained fairly constant over various habitats. It is evident
that both plastic low cost growth traits (internode elongation), and constant high cost traits (internode number) contribute
to the P. palustris escape strategy under tall dense vegetation. Phenotypic plasticity enhances the potential of P. palustris to grow in a wide range of habitats and so increases plant fitness on regional scale. 相似文献
10.
Marcia K. Schmehl Loren Cobb Harvey L. Bank 《In vitro cellular & developmental biology. Plant》1989,25(1):69-75
Summary Six different statistical methods for comparing limiting dilution assays were evaluated, using both real data and a power
analysis of simulated data. Simulated data consisted of a series of 12 dilutions for two treatment groups with 24 cultures
per dilution and 1,000 independent replications of each experiment. Data within each replication were generated by Monte Carlo
simulation, based on a probability model of the experiment. Analyses of the simulated data revealed that the type I error
rates for the six methods differed substantially, with only likelihood ratio and Taswell's weighted mean methods approximating
the nominal 5% significance level. Of the six methods, likelihood ratio and Taswell's minimum Chi-square exhibited the best
power (least probability of type II errors). Taswell's weighted mean test yielded acceptable type I and type II error rates,
whereas the regression method was judged unacceptable for scientific work. 相似文献