共查询到20条相似文献,搜索用时 15 毫秒
1.
2.
3.
4.
Rachid S Huo L Herrmann J Stadler M Köpcke B Bitzer J Müller R 《Chembiochem : a European journal of chemical biology》2011,12(6):922-931
The cinnabaramides and salinosporamides are mixed PKS/NRPS natural products isolated from a terrestrial streptomycete and a marine actinomycete, respectively. They interfere with the proteasome and thus potentially inhibit the growth of cancer cells. The compounds exhibit a γ-lactam-β-lactone bicyclic ring structure attached to a cyclohexenyl unit and a PKS side chain. As a first step towards improving anticancer activity and permitting genetic approaches to novel analogues, we have cloned and characterized the cinnabaramide biosynthetic genes from Streptomyces sp. JS360. In addition to the expected PKS and NRPS genes, the cluster encodes functionalities for the assembly of the hexyl side chain precursor. The corresponding enzymes exhibit relaxed substrate specificities towards a number of synthesized precursors, enabling production of novel chlorinated cinnabaramides. These were isolated and analyzed for activity, revealing that derivatives bearing a chlorine atom in the PKS side chain show higher inhibitory potentials towards the proteasome's proteolytic subunits (especially the trypsin and chymotrypsin units) and higher cytotoxicities towards human tumor cell lines than the parent cinnabaramide A. Although their activities towards the proteasome were weaker than that of salinosporamide A, the cinnabaramides were found to inhibit the growth of various fungi with greater potency. 相似文献
5.
6.
7.
8.
Prof. Dr. Midori A. Arai Kota Sakuraba Yoshinori Makita Dr. Yasumasa Hara Prof. Dr. Masami Ishibashi 《Chembiochem : a European journal of chemical biology》2021,22(18):2799-2804
Pulmonary arterial hypertension (PAH) is a rare and severe progressive disorder characterized by high pulmonary artery pressure. Chronic hypoxia causes a metabolic disorder and the Warburg effect in pulmonary arterial smooth muscle cells (PASMCs). Pyruvate dehydrogenase kinase 1 (PDK1) is a key enzyme in Warburg effect increased by hypoxia-inducible factor (HIF-1). We constructed a cell-based luciferase assay system for HIF-1 inhibitors. Using this system, six HIF-1 inhibitors were identified. Among these inhibitors, the effect of tagitinin C ( 1 ) on PASMC was investigated. Tagitinin C ( 1 ) clearly decreased the amount of HIF-1β and the HIF-1 target PDK1. This result indicates that HIF-1 inhibitors effectively decrease PDK1 activity, which is a cause of the metabolic disorder and Warburg effect observed in PASMCs. Identifying naturally occurring HIF-1 inhibitors could provide novel insights into the development of PAH medications. 相似文献
9.
Karamali Khanbabaee Kerstin Ltzerich Markus Borges Mathias Großer 《Advanced Synthesis \u0026amp; Catalysis》1999,341(2):159-166
The total syntheses of naturally occuring ellagitannins gemin D ( 1 ) and its regioisomer hippomanin A ( 2 ) are reported. In addition, the phase-transfer catalyzed benzylation reaction of the 2,3-glucopyranoside diols 3–7 is described. Our studies have illustrated the influence of the structure of 2,3-glucopyranoside diols on the regioselectivity of the phase-transfer catalyzed benzylation at their free 2,3-OH groups. We could show, that both phase-transfer catalyzed benzylations of 2,3-glucopyranoside diols using tetrabutyl-ammonium hydrogensulfate (Bu4NHSO4) or using tetrabutylammonium iodide (Bu4NI) disfavour the formation of the corresponding 3-O-monobenzylated products and preferrentially give the 2- O-monobenzylated products. However, the ratio of the generated 2- versus 3-O-mono- and 2,3-dibenzylated products from these reactions also strongly depends upon the nature of the starting materials. The glucopyranosides 3 and 4 are the first examples, which allow the completely regioselective monobenzylation at the 2-OH positions by a phase-transfer catalyzed reaction. 相似文献
10.
11.
从天然动植物中提取绿色缓蚀剂的研究进展 总被引:1,自引:0,他引:1
研究了酸洗缓蚀剂的反应机理,阐述了从动植物中提取绿色缓蚀剂的发展历程,展望了天然友好缓蚀剂的发展趋势。以天然植物、海产动植物为原料,提取、分离、加工高效的新型友好环境缓蚀剂,实现资源的优化利用为今后研究的一大方向。 相似文献
12.
Cover Feature: Insights into the Target Interaction of Naturally Occurring Muraymycin Nucleoside Antibiotics (ChemMedChem 8/2018) 下载免费PDF全文
Stefan Koppermann Zheng Cui Patrick D. Fischer Dr. Xiachang Wang Jannine Ludwig Prof. Dr. Jon S. Thorson Prof. Dr. Steven G. Van Lanen Prof. Dr. Christian Ducho 《ChemMedChem》2018,13(8):763-763
13.
Philippe Escavabaja Jacques Viala Yoann Coquerel Jean Rodriguez 《Advanced Synthesis \u0026amp; Catalysis》2012,354(17):3200-3204
Ring rearrangement metathesis (RRM) strategies are proposed for the expeditious synthesis of the cores of naturally occurring cyclic polyethers of the dysiherbaine and acetogenin families, as well as a hybrid compound, from 8‐oxabicyclo[3.2.1]octenes. 相似文献
14.
15.
Towards Tuneable Retaining Glycosidase‐Inhibiting Peptides by Mimicry of a Plant Flavonol Warhead 下载免费PDF全文
Ryoji Yoshisada Lieke van Gijzel Dr. Seino A. K. Jongkees 《Chembiochem : a European journal of chemical biology》2017,18(23):2333-2339
Retaining glycosidases are an important class of enzymes involved in glycan degradation. To study better the role of specific enzymes in deglycosylation processes, and thereby the importance of particular glycosylation patterns, a set of potent inhibitors, each specific to a particular glycosidase, would be an invaluable toolkit. Towards this goal, we detail here a more in‐depth study of a prototypical macrocyclic peptide inhibitor of the model retaining glycosidase human pancreatic α‐amylase (HPA). Notably, incorporation of l ‐DOPA into this peptide affords an inhibitor of HPA with potency that is tenfold higher (Ki=480 pm ) than that of the previously found consensus sequence. This represents a first successful step in converting a recently discovered natural‐product‐derived motif, already specific for the catalytic side‐chain arrangement conserved in the active sites of retaining glycosidases, into a tuneable retaining glycosidase inhibition warhead. 相似文献
16.
17.
18.
Elnakady YA Rohde M Sasse F Backes C Keller A Lenhof HP Weissman KJ Müller R 《Chembiochem : a European journal of chemical biology》2007,8(11):1261-1272
The macrocyclic polyketide kendomycin exhibits antiosteoporotic and antibacterial activity, as well as strong cytotoxicity against multiple human tumor cell lines. Despite the promise of this compound in several therapeutic areas, the cellular target(s) of kendomycin have not been identified to date. We have used a number of approaches, including microscopy, proteomics, and bioinformatics, to investigate the mode of action of kendomycin in mammalian cell cultures. In response to kendomycin treatment, human U-937 tumor cells exhibit depolarization of the mitochondrial membrane, caspase 3 activation, and DNA laddering, consistent with induction of the intrinsic apoptotic pathway. To elucidate possible apoptotic triggers, DIGE and MALDI-TOF were used to identify proteins that are differently regulated in U-937 cells relative to controls. Statistical analysis of the proteomics data by the new web-based application GeneTrail highlighted several significant changes in protein expression, most notably among proteasomal regulatory subunits. Overall, the profile of altered expression closely matches that observed with other tumor cell lines in response to proteasome inhibition. Direct assay in vitro further shows that kendomycin inhibits the chymotrypsin-like activity of the rabbit reticulocyte proteasome, with comparable efficacy to the established inhibitor MG-132. We have also demonstrated that ubiquitinylated proteins accumulate in kendomycin-treated U-937 cells, while vacuolization of the endoplasmic reticulum and mitochondrial swelling are induced in a second cell line derived from kangaroo rat epithelial (PtK(2)) cells, phenotypes classically associated with inhibition of the proteasome. This study therefore provides evidence that kendomycin mediates its cytotoxic effects, at least in part, through proteasome inhibition. 相似文献
19.
Piperdardine 1 and chingchengenamide A 2 , naturally occurring dienamides, are synthesized in 28% and 16% overall yield, respectively, from commercially available safrole 3 . The key steps involve aldol addition to the enal 5 and mild palladium-catalyzed elimination of the carbonates 7 and 10 相似文献