1981-50-6Relevant academic research and scientific papers
A Novel Agonist of the Type 1 Lysophosphatidic Acid Receptor (LPA1), UCM-05194, Shows Efficacy in Neuropathic Pain Amelioration
González-Gil, Inés,Zian, Debora,Vázquez-Villa, Henar,Hernández-Torres, Gloria,Martínez, R. Fernando,Khiar-Fernández, Nora,Rivera, Richard,Kihara, Yasuyuki,Devesa, Isabel,Mathivanan, Sakthikumar,Del Valle, Cristina Rosell,Zambrana-Infantes, Emma,Puigdomenech, María,Cincilla, Giovanni,Sanchez-Martinez, Melchor,Rodríguez De Fonseca, Fernando,Ferrer-Montiel, Antonio V.,Chun, Jerold,López-Vales, Rubén,López-Rodríguez, María L.,Ortega-Gutiérrez, Silvia
, p. 2372 - 2390 (2020/01/02)
Neuropathic pain (NP) is a complex chronic pain state with a prevalence of almost 10% in the general population. Pharmacological options for NP are limited and weakly effective, so there is a need to develop more efficacious NP attenuating drugs. Activation of the type 1 lysophosphatidic acid (LPA1) receptor is a crucial factor in the initiation of NP. Hence, it is conceivable that a functional antagonism strategy could lead to NP mitigation. Here we describe a new series of LPA1 agonists among which derivative (S)-17 (UCM-05194) stands out as the most potent and selective LPA1 receptor agonist described so far (Emax = 118%, EC50 = 0.24 μM, KD = 19.6 nM; inactive at autotaxin and LPA2-6 receptors). This compound induces characteristic LPA1-mediated cellular effects and prompts the internalization of the receptor leading to its functional inactivation in primary sensory neurons and to an efficacious attenuation of the pain perception in an in vivo model of NP.
N-acylated alanine methyl esters (NAMEs) from Roseovarius tolerans, structural analogs of quorum-sensing autoinducers, N-acylhomoserine lactones
Bruns, Hilke,Thiel, Verena,Voget, Sonja,Patzelt, Diana,Daniel, Rolf,Wagner-Doebler, Irene,Schulz, Stefan
, p. 1559 - 1573 (2013/10/21)
The Roseobacter clade is one of the most important bacteria group living in the ocean. Liquid cultures of Roseovarius tolerans EL 164 were investigated for the production of autoinducers such as N-acylhomoserine lactones (AHLs) and other secondary metabolites. The XAD extracts were analyzed by GC/MS. Two AHLs, Z7-C14: 1-homoserine lactone (HSL) and C15: 1-HSL, were identified. Additionally, the extract contained five compounds with molecular-ion peaks at m/z 104, 145, and 158, thus exhibiting mass spectra similar to those of AHLs with corresponding peaks at m/z 102, 143, and 156. Isolation of the main compound by column chromatography, NMR analysis, dimethyl disulfide derivatization for the determination of the location of the CiC bond and finally synthesis of the compound with the proposed structure confirmed the compound to be (Z)-N-(hexadec-9-enoyl)alanine methyl ester. Four additional minor compounds were identified as C14: 0-, C15: 0-, C16: 0-, and C17: 1-N-acylated alanine methyl esters (NAMEs). All NAMEs have not been described from natural sources before. A BLASTp search showed the presence of AHL-producing luxI genes, but no homologous genes potentially responsible for the structurally closely related NAMEs were found. The involvement of the NAMEs in chemical communication processes of the bacteria is discussed. Copyright
Fatty acid desaturation and elongation reactions of trichoderma sp. 1-OH-2-3
Ando, Akinori,Ogawa, Jun,Kishino, Shigenobu,Ito, Taiyo,Shirasaka, Norifumi,Sakuradani, Eiji,Yokozeki, Kenzo,Shimizu, Sakayu
experimental part, p. 227 - 233 (2010/06/16)
The fatty acid desaturation and elongation reactions catalyzed by Trichoderma sp. 1-OH-2-3 were investigated. This strain converted palmitic acid (16:0) mainly to stearic acid (18:0), and further to oleic acid (c9-18:1), linoleic acid (c9,c12-18:2), and α-linolenic acid (c9,c12,c15-18:3) through elongation, and Δ9, Δ12, and Δ15 desaturation reactions, respectively. Palmitoleic acid (c9-16:1) and cis-9,cis-12- hexadecadienoic acid were also produced from 16:0 by the strain. This strain converted n-tridecanoic acid (13:0) to cis-9-heptadecenoic acid and further to cis-9,cis-12-heptadecadienoic acid through elongation, and Δ9 and Δ12 desaturation reactions, respectively. trans-Vaccenic acid (t11-18:1) and trans-12-octadecenoic acid (t12-18:1) were desaturated by the strain through Δ9 desaturation. The products derived from t11-18:1 were identified as the conjugated linoleic acids (CLAs) of cis-9,trans-11-octadecadienoic acid and trans-9,trans-11-octadecadienoic acid. The product derived from t12-18:1 was identified as cis-9,trans-12-octadecadienoic acid. cis-6,cis-9-Octadecadienoic acid was desaturated to cis-6,cis-9,cis-12-octadecatrienoic acid by this strain through Δ12 desaturation. The broad substrate specificity of the elongation, and Δ9 and Δ12 desaturation reactions of the strain is useful for fatty acid biotransformation.
Synthesis and biological characterization of (Z)-9-heptadecenoic and (Z)-6-methyl-9-heptadecenoic acids: Fatty acids with antibiotic activity produced by Pseudozyma flocculosa
Avis,Boulanger,Belanger
, p. 987 - 1000 (2007/10/03)
Difficulties in isolating and purifying antibiotic fatty acids from culture filtrates of Pseudozyma flocculosa, a biocontrol agent against powdery mildew, have been limiting factors in studying the properties and understanding the mode of action of the biocontrol agent. We report a new protocol for synthesizing (Z)-9-heptadecenoic and for the first time synthesis of (Z)-6-methyl-9-heptadecenoic acids, two antibiotic fatty acids produced by P. flocculosa. This allowed reproducible and quantifiable means of assaying biological activity of the molecules. In these bioassays, both molecules exhibited antifungal activity corresponding to their expected potency. These new developments should facilitate further studies aimed at deciphering the ecological properties of P. flocculosa.
