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BS Sabna Thankappan Bency Mahendran Ramasamy Muthusamy Gayathri Femil selta Daniel Raja Angayarkanni Jayaraman 《Probiotics and antimicrobial proteins》2021,13(4):993-1004
Probiotics and Antimicrobial Proteins - Gamma-aminobutyric acid (GABA) is a principal inhibitory neurotransmitter in the central nervous system and is produced by irreversible decarboxylation of... 相似文献
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J. Adam Hendricks Robert N. Hanson Michael Amolins John M. Mihelcic Brian S. Blagg 《Bioorganic & medicinal chemistry letters》2013,23(12):3635-3639
Three novel steroidal antiestrogen–geldanamycin conjugates were prepared using a convergent strategy. The antiestrogenic component utilized the 11β-(4-functionalized-oxyphenyl) estradiol scaffold, while the geldanamycin component was derived by replacement of the 17-methoxy group with an appropriately functionalized amine. Ligation was achieved in high yield using azide alkyne cyclization reactions. Evaluation of the products against two breast cancer cell lines indicated that the conjugates retained significant antiproliferative activity. 相似文献
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Novobiocin was recently shown to inhibit Hsp90 through a previously unrecognized C-terminal ATP binding site. Although the N-terminal region of Hsp90 has been solved by X-ray crystallography, the C-terminal region has not. In an effort to elucidate the C-terminal binding site of Hsp90, four photolabile analogues of novobiocin were prepared. 相似文献
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Adrian Blagg Alan T. Hutton Bernard L. Shaw M. Thornton-Pett 《Inorganica chimica acta》1985,100(2):L33-L34
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Anderson O. Lobo Erica F. Antunes Mariana BS Palma Cristina Pacheco‐Soares Vladimir J. Trava‐Airoldi Evaldo J. Corat 《Cell biology international》2010,34(4):393-398
Monolayer formation of SaOS‐2 (human osteoblast‐like cells) was observed on VACNT (vertically aligned multiwalled carbon nanotubes) scaffolds without purification or functionalization. The VACNT were produced by a microwave plasma chemical vapour deposition on titanium surfaces with nickel or iron as catalyst. Cell viability and morphology studies were evaluated by LDH (lactate dehydrogenase) release assay and SEM (scanning electron microscopy), respectively. The non‐toxicity and the flat spreading with monolayer formation of the SaOs‐2 on VACNT scaffolds surface indicate that they can be used for biomedical applications. 相似文献
6.
Michael J Urban Chengyuan Li Cuijuan Yu Yuanming Lu Joanna M Krise Michelle P McIntosh Roger A Rajewski Brian S J Blagg Rick T Dobrowsky 《ASN neuro》2010,2(4)
Increasing the expression of Hsp70 (heat-shock protein 70) can inhibit sensory neuron degeneration after axotomy. Since the onset of DPN (diabetic peripheral neuropathy) is associated with the gradual decline of sensory neuron function, we evaluated whether increasing Hsp70 was sufficient to improve several indices of neuronal function. Hsp90 is the master regulator of the heat-shock response and its inhibition can up-regulate Hsp70. KU-32 (N-{7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-methoxy-6,6-dimethyl-tetrahydro-2H-pyran-2-yloxy]-8-methyl-2-oxo-2H-chromen-3-yl}acetamide) was developed as a novel, novobiocin-based, C-terminal inhibitor of Hsp90 whose ability to increase Hsp70 expression is linked to the presence of an acetamide substitution of the prenylated benzamide moiety of novobiocin. KU-32 protected against glucose-induced death of embryonic DRG (dorsal root ganglia) neurons cultured for 3 days in vitro. Similarly, KU-32 significantly decreased neuregulin 1-induced degeneration of myelinated Schwann cell DRG neuron co-cultures prepared from WT (wild-type) mice. This protection was lost if the co-cultures were prepared from Hsp70.1 and Hsp70.3 KO (knockout) mice. KU-32 is readily bioavailable and was administered once a week for 6 weeks at a dose of 20 mg/kg to WT and Hsp70 KO mice that had been rendered diabetic with streptozotocin for 12 weeks. After 12 weeks of diabetes, both WT and Hsp70 KO mice developed deficits in NCV (nerve conduction velocity) and a sensory hypoalgesia. Although KU-32 did not improve glucose levels, HbA1c (glycated haemoglobin) or insulin levels, it reversed the NCV and sensory deficits in WT but not Hsp70 KO mice. These studies provide the first evidence that targeting molecular chaperones reverses the sensory hypoalgesia associated with DPN. 相似文献
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Small molecules based upon natural product dimers that exhibit cytotoxic activity were synthesized and evaluated for their anti-proliferative activity in human breast cancer cell lines. A central isophthalic core structure linking aromatic amines containing 3,5-disubstitutions produced the most active compounds. This series of compounds was found to be more active against the estrogen receptor positive cell line MCF-7 than the estrogen receptor negative cell line, SKBr3. 相似文献
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Matts RL Brandt GE Lu Y Dixit A Mollapour M Wang S Donnelly AC Neckers L Verkhivker G Blagg BS 《Bioorganic & medicinal chemistry》2011,19(1):684-692
Several Hsp90 modulators have been identified including the N-terminal ligand geldanamycin (GDA), the C-terminal ligand novobiocin (NB), and the co-chaperone disruptor celastrol. Other Hsp90 modulators elicit a mechanism of action that remains unknown. For example, the natural product gedunin and the synthetic anti-spermatogenic agent H2-gamendazole, recently identified Hsp90 modulators, manifest biological activity through undefined mechanisms. Herein, we report a series of biochemical techniques used to classify such modulators into identifiable categories. Such studies provided evidence that gedunin and H2-gamendazole both modulate Hsp90 via a mechanism similar to celastrol, and unlike NB or GDA. 相似文献
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Blagg JA Noe MC Wolf-Gouveia LA Reiter LA Laird ER Chang SP Danley DE Downs JT Elliott NC Eskra JD Griffiths RJ Hardink JR Haugeto AI Jones CS Liras JL Lopresti-Morrow LL Mitchell PG Pandit J Robinson RP Subramanyam C Vaughn-Bowser ML Yocum SA 《Bioorganic & medicinal chemistry letters》2005,15(7):1807-1810
Through the use of computational modeling, a series of pyrimidinetrione-based inhibitors of MMP-13 was designed based on a lead inhibitor identified through file screening. Incorporation of a biaryl ether moiety at the C-5 position of the pyrimidinetrione ring resulted in a dramatic enhancement of MMP-13 potency. Protein crystallography revealed that this moiety binds in the S(1)(') pocket of the enzyme. Optimization of the C-4 substituent of the terminal aromatic ring led to incorporation of selectivity versus MMP-14 (MT-1 MMP). Structure activity relationships of the biaryl ether substituent are presented as is pharmacokinetic data for a compound that meets our in vitro potency and selectivity goals. 相似文献