Prenylated quinolinecarboxylic acid compound-18 prevents sensory nerve fiber outgrowth through inhibition of the interleukin-31 pathway

Interleukin-31 (IL-31) is involved in excessive development of cutaneous sensory nerves in atopic dermatitis (AD), leading to severe pruritus. We previously reported that PQA-18, a prenylated quinolinecarboxylic acid (PQA) derivative, is an immunosuppressant with inhibition of p21-activated kinase 2 (PAK2) and improves skin lesions in Nc/Nga mice as an AD model. In the present study, we investigate the effect of PQA-18 on sensory nerves in lesional skin. PQA-18 alleviates cutaneous nerve fiber density in the skin of Nc/Nga mice. PQA-18 also inhibits IL-31-induced sensory nerve fiber outgrowth in dorsal root ganglion cultures. Signaling analysis reveals that PQA-18 suppresses phosphorylation of PAK2, Janus kinase 2, and signal transducer and activator of transcription 3 (STAT3), activated by IL-31 receptor (IL-31R), resulting in inhibition of neurite outgrowth in Neuro2A cells. Gene silencing analysis for PAK2 confirms the requirement for STAT3 phosphorylation and neurite outgrowth elicited by IL-31R activation. LC/MS/MS analysis reveals that PQA-18 prevents the formation of PAK2 activation complexes induced by IL-31R activation. These results suggest that PQA-18 inhibits the IL-31 pathway through suppressing PAK2 activity, which suppresses sensory nerve outgrowth. PQA-18 may be a valuable lead for the development of a novel drug for pruritus of AD.

Tolerance of Three Deep South Non-turf Ornamental Groundcovers to Applications of Postemergence Herbicides1

Ornamental groundcovers are a popular alternative to turfgrass in landscapes due to their low maintenance requirements, pest resistance, and shade tolerance. Weed control is a challenge in these groundcovers because few herbicide options are available. The objective of this research was to determine the tolerance of the groundcovers Asiatic jasmine [Trachelospermum asiaticum (Nakai) ‘Minima'], perennial peanut [Arachis pintoi (Krapov.& W.C. Greg.) ‘Golden Glory'] and dwarf mondo grass [Ophiopogon japonicus (L.f.) Ker Gawl.] ‘Nana'] to herbicides, including bentazon, clopyralid, fluazifop-P-butyl, glufosinate, halosulfuron, imazaquin, sethoxydim, sulfentrazone, and sulfosulfuron applied at approximately 2 times the label rate. Asiatic jasmine and perennial peanut were evaluated in Apopka, FL and dwarf mondo grass was evaluated in Mobile, AL. Bentazon, clopyralid, glufosinate, glyphosate, and sulfosulfuron caused unacceptable injury and/or a reduction in shoot growth for all three species while fluazifop-P-butyl and sethoxydim caused no injury to any species. Halosulfuron caused minor injury but significantly reduced growth of dwarf mondo grass. Sulfentrazone caused no injury to Asiatic jasmine or perennial peanut but caused severe injury to dwarf mondo grass after only one application. Similarly, imazaquin caused only minor injury to Asiatic jasmine and dwarf mondo grass but significantly reduced growth of perennial peanut after two applications. Index words: Postemergence herbicides, groundcovers, mondo grass, perennial peanut, Asiatic jasmine. Chemicals used in this study: Bentazon (Basagran® T/O), 3-(1-methylethyl)-1H-2, 1,3-benzothiadiazin-4(3H)-one 2,2-dioxide, clopyralid (Lontrel), 3,6-dichloro-2pyridinecarboxylic acid, fluazifop-P-butyl (Fusilade® II), (2R)-2-[4-[[5-(trifluoromethyl)-2-pyridinyl]oxy]phenoxy]propanoic acid, Glufosinate (Finale®), 2-amino-4-(hydroxymethylphosphinyl)butanoic acid, Glyphosate (Ranger® PRO), N-phosphonomethyl)glycine, Halosulfuron-methyl (SedgeHammer®), methyl 3-chloro-5-[[[[4,6-dimethoxy-2-pyrimidinyl)amino]carbonyl]amino]sulfonyl]-1-methyl-1H-pyrazole-4-carboxylate, Imazaquin (Sceptor® T&O), 2-[4,5-dihydro-4-4-(1-methylethyl)-5-oxo-1H-imidazol-2-yl]-3-quinolinecarboxylic acid, Sethoxydim (Sethoxydim SPC), 2-[1-ethoxyimino)butyl]-5-[2-(ethylthio)propyl]-3-hydroxy-2-cyclohexen-1-one, Sulfentrazone (Dismiss®), N-[2,4-dichloro-5-[4-difluoromethyl)-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazol-1-yl]phenyl]methanesulfonamide, Sulfosulfuron (Certainty®), 1-(4,6-dimethoxypyrimidin-2-yl)-3-[(2-ethanesulfonyl-imidazo[1,2-a]pyridine-3-yl]sulfonylurea. Species used in this study: Asiatic jasmine ‘Minima' (Trachelospermum asiaticum ‘Minima'), perennial peanut (Arachis pintoi ‘Golden Glory'), dwarf mondo grass (Ophiopogon japonicus ‘Nana').

A practical synthesis of 3-chloro-2,4-difluoro-5-hydroxybenzoic acid

A new and practical synthesis of 3-chloro-2,4-difluoro-5-hydroxybenzoic acid, a key intermediate for preparing antimicrobial 3-quinolinecarboxylic acid drugs, is synthesized from 2,4-difluoro-3-chlororobenzoic acid. The protocol involves nitration, esterification, reduction of NO2, diazotization, and hydrolysis with a 70% overall yield. The structures of the synthesized compounds are determined by infrared spectroscopy, nuclear magnetic resonance spectroscopy, and high-resolution electrospray ionization mass spectrometry. The advantages of this developed synthetic strategy include an improved overall yield and readily controllable reaction conditions.

Azo compounds based on 2-(4'-aminophenyl)-4-quinoline carboxylic acid: synthesis and properties

Synthesis and studies of the properties of dyes for coloring textile materials from fibers of various chemical structures, which contain, in addition to chromophore, also pharmacophore groups in the molecule, which impart biocidal properties to both the dyes themselves and the materials dyed by them, are interesting both theoretically and from an applied point of view. The article presents data on the synthesis of a series of previously undescribed azo compounds based on 2-(4'-aminophenyl)-4-quinolinecarboxylic acid and aromatic hydroxy- and aminocompounds of the naphthalene series. Five naphthylazo derivatives of 2-(4'-aminophenyl)-4-quinolinecarboxylic acid were synthesized in high yields. The structures of the synthesized azo compounds were confirmed by mass-spectrometry and UV-spectroscopy. In the electronic absorption spectra, the absorption maximum of the synthesized azo compounds lies in the range of 480-550 nm, in contrast to the initial diazo and azo components, the absorption maxima of which lie in the near UV region of the spectrum. Dyeing techniques have been developed that provide optimal indicators for the process of coloration of polypeptide fibers (wool and nylon) with synthesized dyes. The colors of the samples have bright, and deep colors of orange-red-violet scales. The obtained painted samples were examined for color fastness to wet processing according to GOST 9733.4-83, sweat GOST 9733.6-83 and light exposure GOST 11279.2-83. It has been shown that the synthesized azo compounds can be used for coloring woolen and polyamide fibers and provide satisfactory performance properties of dyes, which is consistent with generally accepted ideas about acid dyes. Samples of dyed polyamide fabric showed satisfactory color fastness to light (1-3 points), the best result was shown by wool samples dyed with the studied dyes.