다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

Natural products and their structural analogues have historically made a major contribution to pharmacotherapy, especially for cancer and infectious diseases. Nevertheless, natural products also present challenges for drug discovery, such as technical barriers to screening, isolation, characterization and optimization, which contributed to a decline in their pursuit by the pharmaceutical industry from the 1990s onwards. In recent years, several technological and scientific developments — including improved analytical tools, genome mining and engineering strategies, and microbial culturing advances — are addressing such challenges and opening up new opportunities. Consequently, interest in natural products as drug leads is being revitalized, particularly for tackling antimicrobial resistance. Here, we summarize recent technological developments that are enabling natural product-based drug discovery, highlight selected applications and discuss key opportunities. Natural products have historically made a major contribution to pharmacotherapy, but also present challenges for drug discovery, such as technical barriers to screening, isolation, characterization and optimization. This Review discusses recent technological developments — including improved analytical tools, genome mining and engineering strategies, and microbial culturing advances — that are enabling a revitalization of natural product-based drug discovery.

/pdf/natural-products-in-drug-discovery-advances-and-4axj6y2vp0.pdf

Natural products in drug discovery: advances and opportunities.

Natural products have been a rich source of compounds for drug discovery. However, their use has diminished in the past two decades, in part because of technical barriers to screening natural products in high-throughput assays against molecular targets. Here, we review strategies for natural product screening that harness the recent technical advances that have reduced these barriers. We also assess the use of genomic and metabolomic approaches to augment traditional methods of studying natural products, and highlight recent examples of natural products in antimicrobial drug discovery and as inhibitors of protein-protein interactions. The growing appreciation of functional assays and phenotypic screens may further contribute to a revival of interest in natural products for drug discovery.

/pdf/the-re-emergence-of-natural-products-for-drug-discovery-in-1h0jebzmkp.pdf

The re-emergence of natural products for drug discovery in the genomics era

Actinobacteria are Gram-positive bacteria with high G+C DNA content that constitute one of the largest bacterial phyla, and they are ubiquitously distributed in both aquatic and terrestrial ecosystems. Many Actinobacteria have a mycelial lifestyle and undergo complex morphological differentiation. They also have an extensive secondary metabolism and produce about two-thirds of all naturally derived antibiotics in current clinical use, as well as many anticancer, anthelmintic, and antifungal compounds. Consequently, these bacteria are of major importance for biotechnology, medicine, and agriculture. Actinobacteria play diverse roles in their associations with various higher organisms, since their members have adopted different lifestyles, and the phylum includes pathogens (notably, species of Corynebacterium, Mycobacterium, Nocardia, Propionibacterium, and Tropheryma), soil inhabitants (e.g., Micromonospora and Streptomyces species), plant commensals (e.g., Frankia spp.), and gastrointestinal commensals (Bifidobacterium spp.). Actinobacteria also play an important role as symbionts and as pathogens in plant-associated microbial communities. This review presents an update on the biology of this important bacterial phylum.

/pdf/taxonomy-physiology-and-natural-products-of-actinobacteria-1arwsidgil.pdf

Taxonomy, Physiology, and Natural Products of Actinobacteria

Tissues are dynamically shaped by bidirectional communication between resident cells and the extracellular matrix (ECM) through cell-matrix interactions and ECM remodelling. Tumours leverage ECM remodelling to create a microenvironment that promotes tumourigenesis and metastasis. In this review, we focus on how tumour and tumour-associated stromal cells deposit, biochemically and biophysically modify, and degrade tumour-associated ECM. These tumour-driven changes support tumour growth, increase migration of tumour cells, and remodel the ECM in distant organs to allow for metastatic progression. A better understanding of the underlying mechanisms of tumourigenic ECM remodelling is crucial for developing therapeutic treatments for patients.

/pdf/concepts-of-extracellular-matrix-remodelling-in-tumour-2m26t5qipg.pdf

Concepts of extracellular matrix remodelling in tumour progression and metastasis

Fluorinated 1,5-Dihydro-pyrrol-2-ones J a -Philippe Bouillon,*a Bernard Tinant,b Jean-Marc Nuzillard,c Charles Portellaa a Laboratoire ‘Réactions Sélectives et Applications’, UMR CNRS 6519, Université de Reims, Faculté des Sciences B.P. 1039, 51687 Reims Cedex 2, France Fax +33(3)26913166; E-mail: jp.bouillon@univ-reims.fr b Université Catholique de Louvain, Laboratoire de Chimie Physique et de Cristallographie, 1 Place Louis Pasteur, 1348 Louvain-laNeuve, Belgium c Laboratoire de Pharmacognoise, UMR CNRS 6013, Université de Reims, Faculté des Sciences, Batiment 18, Moulin de las Housse B. P. 1039, 51687 Reims Cedex 2, France Received 17 November 2003; revised 12 January 2004

Synthesis of New 3-(1-Ethylsulfanyl-2-perfluoroalkyl)-5-hydroxy-5-methyl (or 5-phenyl)-1,5-dihydro-pyrrol-2-ones Starting from γ-Keto Thioesters and Amines.

. The heteronuclear single quantum correlation (HSQC) experiment developed by Bodenhausen and Ruben (1980) in the early days of modern nuclear magnetic resonance (NMR) is without a doubt one of the most widely used experiments, with applications in almost every aspect of NMR including metabolomics. Acquiring this experiment, however, always implies a trade-off: simplification versus resolution. Here, we present a method that artificially lifts this barrier and demonstrate its application towards metabolite identification in a complex mixture. Based on the measurement of clean in-phase and clean anti-phase (CLIP/CLAP) HSQC spectra (Enthart et al., 2008), we construct a virtually decoupled HSQC (vd-HSQC) spectrum that maintains the highest possible resolution in the proton dimension. Combining this vd-HSQC spectrum with a J -resolved spectrum (Pell and
Keeler, 2007) provides useful information for the one-dimensional proton
spectrum assignment and for the identification of metabolites in Dreissena polymorpha (Prud'homme
et al., 2020).

/pdf/virtual-decoupling-to-break-the-simplification-versus-2lay6tfnhw.pdf

Virtual decoupling to break the simplification versus resolution trade-off in nuclear magnetic resonance of complex metabolic mixtures

The application of a biselective radiofrequency pulse to a coupled homonuclear spin system produces effects that are exploited in liquid-state NMR experiments. The insertion of such an RF pulse in a double pulsed field gradient spin echo sequence results in a module for the biselective production of antiphase magnetization states. Biselectivity is obtained through cosine modulation of a singly selective pulse profile. A full description of the module behaviour is possible by means of four parameters, of which two are related to a property called ‘pulse ellipticity’. The theory is in good agreement with the experimental results and numerical simulations. It is thus possible to predict how a maximum of antiphase magnetization can be produced.

/pdf/a-theoretical-study-of-the-biselective-double-pulsed-field-ufgnhhw46m.pdf

A Theoretical Study of the Biselective Double Pulsed Field Gradient Spin-Echo NMR Experiment

Large-scale isolation of anthocyanins from grapevine by strong ion-exchange centrifugal partition chromatography

Predicted carbon-13 NMR data of Natural Products (PNMRNP)

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