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131.
Kumar V Rani N Aggarwal P Sanna VK Singh AT Jaggi M Joshi N Sharma PK Irchhaiya R Burman AC 《Bioorganic & medicinal chemistry letters》2008,18(18):5058-5062
A new series of betulinic acid derivatives have been synthesized by introducing heterocyclic ring between C-2 and C-3 positions of betulinic acid. Further modifications were also carried out by reduction of C-20(29) unsaturated bond and substitution of C-28 carboxyl group by ester and amide linkage to enhance the selectivity. Compound 11 resulted in IC(50) of 2.44, 2.5, and 2.7 microg/ml on MIAPaCa, PA-1, and SW620 cancer cell lines, respectively. Compound 38 resulted in IC(50) of 0.67 microg/ml on MIAPaCa cell line. 相似文献
132.
Pramod K. Dash † Beth A. Traxler ‡ Mitradas M. Panicker § David D. Hackney Edwin G. Minkley Jr 《Molecular microbiology》1992,6(9):1163-1172
The gene product of F tral is a bifunctional protein which nicks and unwinds the F plasmid during conjugal DNA transfer. Further biochemical characterization of the Tral protein reveals that it has a second, much lower, Km for ATP hydrolysis, in addition to that previously identified. Measurement of the single-stranded DNA-stimulated ATPase rate indicates that there is co-operative interaction between the enzyme monomers for maximal activity. Furthermore, 18O-exchange experiments indicate that Tral protein hydrolyses ATP with, at most, a low-level reversal of the hydrolytic step during each turnover. 相似文献
133.
A theoretical investigation of capillary-tissue fluid exchange has been studied including the characteristics and influence of the boundaries and media through which the fluid flows. Filtration from a cylindrical capillary into the concentrically surrounding tissue space and flow from a capillary into the tissue across a thin membrane are analyzed in detail. In has been observed that the filtration efficiency of the functional unit decreases as the viscosity of the peripheral layer increases. Contrary to the results of Apelblat [17], the slip velocity at the porous boundary plays a dominant role in filtration efficiency. It has also been noticed that the filtration efficiency decreases as the slip velocity at the porous boundary increases. 相似文献
134.
135.
Sougata Ghosh Piyush More Abhishek Derle Ajay B. Patil Pramod Markad Adersh Asok Navanath Kumbhar Mahemud L. Shaikh Boppana Ramanamurthy Vaishali S. Shinde Dilip D. Dhavale Balu A. Chopade 《PloS one》2014,9(9)
Diabetes mellitus is a multifactorial metabolic disease characterized by post-prandial hyperglycemia (PPHG). α-amylase and α-glucosidase inhibitors aim to explore novel therapeutic agents. Herein we report the promises of Dioscorea bulbifera and its bioactive principle, diosgenin as novel α-amylase and α-glucosidase inhibitor. Among petroleum ether, ethyl acetate, methanol and 70% ethanol (v/v) extracts of bulbs of D. bulbifera, ethyl acetate extract showed highest inhibition upto 72.06 ± 0.51% and 82.64 ± 2.32% against α-amylase and α-glucosidase respectively. GC-TOF-MS analysis of ethyl acetate extract indicated presence of high diosgenin content. Diosgenin was isolated and identified by FTIR, 1H NMR and 13C NMR and confirmed by HPLC which showed an α-amylase and α-glucosidase inhibition upto 70.94 ± 1.24% and 81.71 ± 3.39%, respectively. Kinetic studies confirmed the uncompetitive mode of binding of diosgenin to α-amylase indicated by lowering of both Km and Vm. Interaction studies revealed the quenching of intrinsic fluorescence of α-amylase in presence of diosgenin. Similarly, circular dichroism spectrometry showed diminished negative humped peaks at 208 nm and 222 nm. Molecular docking indicated hydrogen bonding between carboxyl group of Asp300, while hydrophobic interactions between Tyr62, Trp58, Trp59, Val163, His305 and Gln63 residues of α-amylase. Diosgenin interacted with two catalytic residues (Asp352 and Glu411) from α-glucosidase. This is the first report of its kind that provides an intense scientific rationale for use of diosgenin as novel drug candidate for type II diabetes mellitus. 相似文献
136.
Identification of glycoprotein IV (CD36) as a primary receptor for platelet-collagen adhesion 总被引:23,自引:0,他引:23
The role of glycoprotein IV (GPIV) in platelet activation processes has been examined by several different approaches: (i) Fab fragments of a monospecific polyclonal antibody to purified platelet GPIV (approximately 20 micrograms/ml) completely inhibited platelet shape change, aggregation, and secretion induced by collagen. Aggregation and secretion by ADP (but not shape change) and by epinephrine were also inhibited, but there was no effect on platelet activation induced by thrombin, arachidonate, or ionophore A23187. (ii) Purified GPIV was able to compete completely with membrane-bound GPIV to inhibit platelet activation induced by collagen, including shape change, but not in activation induced by any of the other platelet agonists. 50% inhibition of collagen-induced activation and secretion were obtained at GPIV concentrations of approximately 10 nM (1 micrograms/ml). (iii) Purified GPIV bound rapidly and reversibly to collagen Type I fibrils, and binding was not inhibited by adhesive proteins such as denatured collagen, fibronectin, fibrinogen, or von Willebrand factor. The direct binding of purified GPIV to collagen Type I fibrils fit best to a single site model with Kd 0.34 +/- 0.10 nM. (iv) Using a microtiter assay, platelet adhesion to collagen was shown to be inhibited by Fab fragments of monospecific polyclonal anti-GPIV antibodies, but adhesion to other adhesive proteins was unaffected. (v) When anti-GPIV was added at various times during adhesion the time dependence of inhibition was seen to be biphasic. Anti-GP antibody was able to reverse adhesion that occurred within the first 5-8 min and to inhibit adhesion occurring thereafter. These results demonstrate that GPIV mediates the early stages of platelet recognition by and attachment to collagen but that there may be a second GPIV-independent mechanism that mediates the subsequent anchorage of these adherent platelets. 相似文献
137.
G. Gopinath A. K. Mahapatra J. C. Bharadwaj R. Banerji D. N. Sharma P. N. Tandon 《Journal of biosciences》1989,14(3):255-260
A feasibility study of neural transplantation in adult rhesus monkey was undertaken. Fresh and preserved neocortex containing
multiplying and maturing neurons obtained from 55–70 gestation days were transplanted into the striatum, cerebellum and cerebral
cortex of adult monkeys. Tissues were preserved for 4 days either at subzero temperature in the freezer compartment of the
ordinary refrigerator in Ringer lactate or incubated in culture medium. While 2 monkeys out of 5 injected with preserved tissue
had successful transplants after 4 months, all the 10 monkeys injected with fresh tissue had no transplants. The size of the
two surviving transplants was small. The neurons in the transplants were mainly in clusters. Many of the cells were immature
and some showed early degenerative changes. Neuronal processes were restricted to the transplants and thus showed lack of
morphological integration with the host tissue. Further studies are in progress to define the nature of the embryonic tissue
of primate which can grow and survive and also the role of neural grafts in functional recovery following experimental lesions
of the brain regions. 相似文献
138.
139.
Pramod Kumar Yadav Peter Xie Ruma Banerjee 《The Journal of biological chemistry》2012,287(45):37611-37620
Human cystathionine β-synthase (CBS) is a unique pyridoxal 5′-phosphate (PLP)-dependent enzyme that has a regulatory heme cofactor. Previous studies have demonstrated the importance of Arg-266, a residue at the heme pocket end of α-helix 8, for communication between the heme and PLP sites. In this study, we have examined the role of the conserved Thr-257 and Thr-260 residues, located at the other end of α-helix 8 on the heme electronic environment and on activity. The mutations at the two positions destabilize PLP binding, leading to lower PLP content and ∼2- to ∼500-fold lower activity compared with the wild-type enzyme. Activity is unresponsive to PLP supplementation, consistent with the pyridoxine-nonresponsive phenotype of the T257M mutation in a homocystinuric patient. The H2S-producing activities, also impacted by the mutations, show a different pattern of inhibition compared with the canonical transsulfuration reaction. Interestingly, the mutants exhibit contrasting sensitivities to the allosteric effector, S-adenosylmethionine (AdoMet); whereas T257M and T257I are inhibited, the other mutants are hyperactivated by AdoMet. All mutants showed an increased propensity of the ferrous heme to form an inactive species with a 424 nm Soret peak and exhibited significantly reduced enzyme activity in the ferrous and ferrous-CO states. Our results provide the first evidence for bidirectional transmission of information between the cofactor binding sites, suggest the additional involvement of this region in allosteric communication with the regulatory AdoMet-binding domain, and reveal the potential for independent modulation of the canonical transsulfuration versus H2S-generating reactions catalyzed by CBS. 相似文献
140.
The influence of dietary nicotinamide deficiency on lead intoxication in young developing rats was investigated. The Pb induced
an increase in brain dopamine and noradrenaline, inhibition in blood δ-aminolevulinic acid dehydratase activity, an elevation
in urinary excretion of δ-aminolevulinic acid and blood and tissue uptake of Pb were significantly more marked in animals
maintained on a nicotinamide-deficient diet than those fed a nicotinamide-sufficient diet. The nicotinamide deficiency may
enhance the susceptibility to Pb intoxication possible by enhancing the absorption of Pb and altering nicotinic acid metabolism. 相似文献