9^{th European Chemistry Congress} June 17-18, 2019 | Golden Tulip Berlin- Hotel Hamburg | Berlin, Germany

Liliia M Kril is a Senior Research Technician in the Department of Molecular and Cellular Biochemistry at the University of Kentucky (USA) in Professor D.S. Watt’s laboratory. She contributes to several, on-going drug development projects and her scientific contribution led to the development of novel MAT2A and tubulin inhibitors as promising anticancer agents as well as to the discovery of (N-amidinohydrazones) and N-(amidino)-N′-aryl-bishydrazones as new classes of antibacterial/antifungal agents. She is co-author of numerous papers published in peer-reviewed journals.

Colorectal cancer (CRC) is the third leading cause of cancer-related mortality worldwide. CRC is initiated by mutations of the tumor suppressor gene, adenomatous polyposis coli (APC), or β-catenin gene. These mutations stabilize β-catenin and constitutively activate Wnt/β -catenin target genes, such as c-Myc and cyclin D1, ultimately leading to cancer. We developed a family of fluorinated diarylacetylene agents, called FIDAS agents, that inhibit the proliferation of CRC cells in vitro at nanomolar levels and in vivo at a dosage of 20 mg/kg. Using a biotinylated FIDAS analogue, we identified the catalytic subunit (MAT2A) of MAT2 as the direct and exclusive binding target of these diarylacetylene-based FIDAS agents. Structure-activity relationships defined the nature of aryl and heteroaryl rings as well as the substituents on these rings associated with potency as MAT2 inhibitors. MAT2 is up-regulated in many cancers, including liver cancers and colorectal cancers (CRC) and is a potentially important drug target. FIDAS agents inhibited MAT2 selectively without affecting MAT1 that supplies SAM for most cellular needs. Validation of MAT2 as a cancer target relied on the observation that shRNAs also inhibited CRC cell growth. A diarylacetylene-based FIDAS agent delivered orally repressed CRC and hepatocellular cancer xenografts in athymic nude mice. These findings suggest that diarylacetylene-based FIDAS analogs function as epigenetic regulators by targeting MAT2 and represent a family of novel and potentially useful agents for cancer treatment.

Zhiyong Hu has completed his master degree at the age of 26 years from East China University of Science and Technology in China. During his master studying, he worked at Shanghai Institute Of Organic Chemistry for two years. Now he is a PhD student in Ruhr-Universität Bochum followed by Lukas J. Gooßen as the supervisor.

In the presence of a [Cp*RhCl2]2 catalyst, the Lewis acid In(OTf)3, and the mild base Na2CO3, aromatic carboxylates and α,β-unsaturated ketones undergo a unique hydroarylation/Claisen/retro-Claisen process to give the corresponding indanones. In this carboxylate-directed ortho-C_H annelation, the C_COR bond of the ketone and the CO_OH group of the aromatic carboxylate are cleaved, and the hydroxy group is transferred from the aromatic to the aliphatic acyl residue. This reactivity is synthetically useful, particularly when starting from cyclic ketones, which are converted into indanones bearing aliphatic carboxylate side chains, thus greatly increasing the molecular complexity of aromatic carboxylates in a single step.

Mario Komar has completed his MSc at Department of Chemistry in Osijek, Croatia. He is a PhD student at Faculty of Chemical Engineering and Technology in Zagreb and works as Assistant on the Faculty of Food Technology in Osijek. The main subject of his research is application of deep eutectic solvents in organic synthesis. He has published two papers in reputed journals

1,2,4-Triazoles, a heterocyclic compounds with a wide range of biological activities such as antibacterial, antifungal, antitumor, anticolvulsant, antiinflammatory and antimicrobial, exist in two tautomeric forms, 1H and 4H. Until recently, these heterocycles are usually prepared from 1,2,4-oxadiazoles in reaction with hydrazine, 1,3,4-oxadiazoles and hydrazides or thiosemicarbazides in basic conditions. Hereby, we report a synthesis of 1,2,4-triazoles in deep eutectic solvents. DES is a mixture of a salt, usually chloline chloride wich is hydrogen bond acceptor (HBA) and a hydrogen bond donor (HBD) such as alcohols, sugars, amides and carboxyl acids, which mostly exist as liquid at or below 100°C. A model reaction between 2-((4-methyl-2-oxo-2H-chromen-7-yl)oxy)acetohydrazide and phenyl isothiocyanate was carried out on two different temperatures (40°C and 80°C) in 14 choline chloride based deep eutectic solvents (DESs). Pure thiosemicarbazide was formed in choline chloride:malonic acid (1:1), choline chloride:malic acid (1:1) and DESs with different alcohols as HBDs. The best conversion to 1,2,4-triazole derivatives was obtained in choline chloride:urea (1:2) at 80°C, so this DES was used for next synthesis of 1,2,4-triazoles with various isothiocyanates and hydrazides.

Shuohan Huang will attain her Master Degree in Medcine in June 30, 2019 from School of Pharmacy, Nanjing Medical University. Her current interest focuses on the single cell analysis, espeiclally the membrane lipids analysis in single cells in the lipid related dieases such as atherosclerosis.She has published three papers on international journals, including one on Analytical Chemistry.

Phosphatidylcholine (PC) and sphingomyelin (SM) are two important phospholipid components of cell membranes that are positively correlated with cardiovascular diseases. In the current enzymatic quantification method, PC and SM first react with specific enzymes to generate choline and then the choline is irreversibly catalyzed by choline oxidase into hydrogen peroxide and glycine betaine. The lipid content was measured by detecting the amount of peroxidase. However, plasma, tissue and cell membrane all contain a small amount of choline that may confound the measurement of PC and SM. Attempts were made utilizing lipid extraction methods to avoid possible interference of membrane choline, but they yielded conclusions that are often inaccurate. Herein, we describe a rapid, specific and sensitive method to measure membrane choline in living cells by using luminol electrochemiluminescence (ECL). We also employ a pretreatment strategy using choline oxidase to avoid possible interference from membrane choline. The successful removal of choline in the cell membranes was verified. This strategy may serve as a new method for the accurate determination of PC, SM, and membrane choline in the living cells, allowing a precise understanding of the biological roles of these molecules in cell membranes.

Jee Young Kim has completed her PhD from Saga University, Japan in 2015 and Postdoctoral studies from Pusan National University, South Korea. Her research interest lies on interfacial behavior and solvent extraction kinetics with various types’ calix [4] arene derivatives.

The solvent extraction kinetics of silver with methyl ketonic p-tert-octylcalix [4] arene as a hydrophobic extractant has been studied using a modified Lewis cell system. The effects of parameters affecting the extraction efficiency such as stirring speed, temperature and silver concentration were investigated. The initial extraction efficiency was rapidly increased as the stirring speed increased to 170 rpm, then a plateau in the efficiency occurred, which represents the crossover point between diffusion and chemical reaction control at the liquid-liquid interface. The thermodynamic parameters indicated that the adsorption process was spontaneous and exothermic.

Dejan Popovic is from University of Nis, Serbia.

The protective activity of the anthocyanins from the bilberry extract in the acute liver damage in rats caused by CCl4 (1.5 mL/kg i.p.) was examined. The mechanism of the acute hepatotoxicity was based on an excessive production of the reactive metabolites CCl4, which led to the morphological liver cells damage through the lipid peroxidation induction and oxidative stress. The membrane damage caused the enzyme leakage from the hepatocytes and increased activity of AST and ALT in the serum. The acute CCl4 poisoning resulted in a significant increase of the pro-oxidative (MDA and GSSG) and a decrease of the anti-oxidative (GSH, CAT, SOD, GST, GPx, and GR) markers in the liver. The CCl4 toxic effects caused the massive perivenular coagulation necrosis followed by micro and microvesicular fatty changes in the periportal region. The protective use of the bilberry extract (100 mg/kg of the oral ten-day treatment with anthocyanins) prior to the administration with the toxic CCl4 resulted in an evident decrease of the pro-oxidative markers, as well as a significant decrease of the dissipation of the liver anti-oxidative defence capacities in comparison to the results detected in the animals treated with CCl4 exclusively. The pathohistological changes were described as less serious reversible hydropic changes characterized by an evident absence of the necrosis. The protective effect of the anthocyanins was based on the neutralization of the highly reactive CCl4 metabolites by adding the hydrogen atom from the hydroxyl groups of delphinidin from the anthocyanin.