14464-30-3Relevant articles and documents
Synthesis and biological activities of 6-amino- and 6-(acylamino)-N-acetylmuramyl dipeptides
Hasegawa,Okumura,Kiso,et al.
, p. 1309 - 1313 (1980)
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Isolation and synthesis of N-acyladenine and adenosine alkaloids from a southern Australian marine sponge, Phoriospongia sp.
Farrugia, Michelle,Trotter, Nicholas,Vijayasarathy, Soumini,Salim, Angela A.,Khalil, Zeinab G.,Lacey, Ernest,Capon, Robert J.
, p. 5902 - 5904 (2014)
Chemical fractionation of the southern Australian marine sponge Phoriospongia sp. (CMB-03107) yielded phorioadenine A (1) as a nematocidal agent and the first reported example of a 6-N-acyladenine natural product. The structure of 1 was confirmed by spectroscopic analysis and the chemical synthesis of racemic (1a) and enantiomeric (1b) analogues. HPLC-ESIMS analysis of the crude sponge extract with comparisons to the synthetic 6-N-acyladenosine 2a provided evidence that the biosynthetically related adenosine, phorioadenosine A (2), was present as a trace co-metabolite. The rare starfish metabolite asterubine (3) was also isolated as a co-metabolite, and its structure confirmed by spectroscopic analysis and chemical synthesis. Biological investigations confirmed that natural products 1-3 and synthetic analogues 1a-e and 2a were not cytotoxic to multiple mammalian cancer cell lines, or Gram-positive or -negative bacteria. Nematocidal activity (inhibition of larval development of Haemonchus contortus) detected in the Phoriospongia sp. extract was attributed to 1 (LD9931 μg/mL), with preliminary structure-activity relationship investigations confirming the importance of the N-acyl side chain.
Synthesis and Characterization of Fatty Acid Grafted Chitosan Polymer and Their Nanomicelles for Nonviral Gene Delivery Applications
Sharma, Divya,Singh, Jagdish
, p. 2772 - 2783 (2017)
The aim of this study was to synthesize and characterize fatty acid-grafted-chitosan (fatty acid-g-CS) polymer and their nanomicelles for use as carriers for gene delivery. CS was hydrophobically modified using saturated fatty acids of increasing fatty acyl chain length. Carbodiimide along with N-hydroxysuccinimide was used for coupling carboxyl group of fatty acids with amine groups of CS. Proton nuclear magnetic resonance and Fourier transform infrared spectroscopy were used to quantify fatty acyl substitution onto CS backbone. The molecular weight distribution of the synthesized polymers was determined using size exclusion high performance liquid chromatography and was found to be in range of the parent CS polymer (～50 kDa). The critical micelle concentration (cmc) of the polymers was determined using pyrene as a fluorescent probe. The cmc was found to decrease with an increase in fatty acyl chain length. The amphiphilic fatty acid-g-CS polymers self-assembled in an aqueous environment to form nanomicelles of ～200 nm particle size and slightly positive net charge due to the cationic nature of free primary amino groups on CS molecule. These polymeric nanomicelles exhibited excellent hemo- and cytocompatibility, as evaluated by in vitro hemolysis and MTT cell viability assay, respectively, and showed superior transfection efficiency compared to unmodified chitosan and naked DNA. The surface of these nanomicelles can be further modified with ligands allowing for selective targeting, enhanced cell binding, and internalization. These nanomicelles can thus be exploited as potential nonviral gene delivery vectors for safe and efficient gene therapy.
Development of small-molecule inhibitors of fatty acyl-AMP and fatty acyl-CoA ligases in Mycobacterium tuberculosis
Aldrich, Courtney C.,Baran, Marzena,Boshoff, Helena I. M.,Fu, Peng,Grimes, Kimberly D.,Sibbald, Paul A.,Wilson, Daniel J.
, (2020/06/29)
Lipid metabolism in Mycobacterium tuberculosis (Mtb) relies on 34 fatty acid adenylating enzymes (FadDs) that can be grouped into two classes: fatty acyl-CoA ligases (FACLs) involved in lipid and cholesterol catabolism and long chain fatty acyl-AMP ligases (FAALs) involved in biosynthesis of the numerous essential and virulence-conferring lipids found in Mtb. The precise biochemical roles of many FACLs remain poorly characterized while the functionally non-redundant FAALs are much better understood. Here we describe the systematic investigation of 5′-O-[N-(alkanoyl)sulfamoyl]adenosine (alkanoyl adenosine monosulfamate, alkanoyl-AMS) analogs as potential multitarget FadD inhibitors for their antitubercular activity and biochemical selectivity towards representative FAAL and FACL enzymes. We identified several potent compounds including 12-azidododecanoyl-AMS 28, 11-phenoxyundecanoyl-AMS 32, and nonyloxyacetyl-AMS 36 with minimum inhibitory concentrations (MICs) against M. tuberculosis ranging from 0.098 to 3.13 μM. Compound 32 was notable for its impressive biochemical selectivity against FAAL28 (apparent Ki = 0.7 μM) versus FACL19 (Ki > 100 μM), and uniform activity against a panel of multidrug and extensively drug-resistant TB strains with MICs ranging from 3.13 to 12.5 μM in minimal (GAST) and rich (7H9) media. The SAR analysis provided valuable insights for further optimization of 32 and also identified limitations to overcome.
Synthesis of UDP-glucose: N-acylsphingosine glucosyl transferase inhibitors
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Page/Page column 24, (2017/02/09)
Disclosed is a novel enantiomeric synthesis ceramide-like inhibitors of UDP-glucose: N-acylsphingosine glucosyltransferase. Also disclosed are novel intermediates formed during the synthesis.
