Contribution of the Laboratory of Organic Chemistry in the effort to fight diseases (T. Mavromoustakos Group)

1. Enhancing the treatment of glioblastoma polymorphism through rational design of the quercetin-losartan hybrid composition.

An article has been recently published in the journal Free Radical Biology and Medicine 160 (2), 391-402 (impact index in 2019 6.17 and last five years 6.46), entitled “Enhancing the treatment of polio glioblastoma through a quercetin hybrid –losartan”. In this article the team of the Laboratory of Organic Chemistry collaborated under the guidance of T. Mavromoustakos where rational drug design through Molecular Docking was performed, the team of Associate Professor A. Tzakos, under whose guidance the hybrid molecule was synthesized, conducting biological tests by the Departments of Medicine, Molecular Biology and Biotechnology and Biology of the University of Ioannina, the John Fulcher Neuro-Oncology Laboratory, Imperial College London, Hammersmith Hospital, London, UK and Monash Biomedicine Discovery Institute and Department of Biochemistry and M , Monash University, Clayton, VIC, 3800, Australia.

A brief summary of the research work is given below: Glioblastoma multiforme (GBM) is the most common and aggressive primary malignant brain tumor. Maximal surgical resection followed by radiotherapy and concomitant chemotherapy with temozolomide remains the first-line therapy, prolonging the survival of patients by an average of only 2.5 months. There is therefore an urgent need for novel therapeutic strategies to improve clinical outcomes. Reactive oxygen species (ROS) are an important contributor to GBM development. Here, we describe the rational design and synthesis of a stable hybrid molecule tethering two ROS regulating moieties, with the aim of constructing a chemopreventive and anticancer chemical entity that retains the properties of the parent compounds. We utilized the selective AT1R antagonist losartan, leading to the inhibition of ROS levels, and the antioxidant flavonoid quercetin. In GBM cells, we show that this hybrid retains the binding potential of losartan to the AT1R through competition-binding experiments and simultaneously exhibits ROS inhibition and antioxidant capacity similar to native quercetin. In addition, we demonstrate that the hybrid is able to alter the cell cycle distribution of GBM cells, leading to cell cycle arrest and to the induction of cytotoxic effects. Last, the hybrid significantly and selectively reduces cancer cell proliferation and angiogenesis in primary GBM cultures with respect to the isolated parent components or their simple combination, further emphasizing the potential utility of the current hybridization approach in GBM.

2. Discovery of chemical compounds with dual inhibitory activity of TNF and RANKL, two proteins that are major targets for the treatment of chronic inflammatory diseases.

Distinction of published work: G. Melagraki, E. Ntougkos, V. Rinotas, C. Papaneophytou, G. Leonis, T. Mavromoustakos, G. Kantopidis, E. Douni, A. Afantitis, G. Kol. Cheminformatics-aided discovery of small-molecule protein-protein interaction (PPI) dual inhibitors of Tumor Necrosis Factor (TNF) and receptor activator of NF-κB B ligand (RANKL). PLOS Computational Biology 13 (4), e1005372 (2017). (I.F 2020 4.380). This article is among the top 10% published in the internationally renowned journal PLOS Computational Biology published in 2017.

Congratulations Thomas!
Your article is among the top 10% most cited PLOS Computational Biology papers published in 2017.

Cheminformatics-Aided Discovery of Small-Molecule Protein-Protein Interaction (PPI) Dual Inhibitors of Tumor Necrosis Factor (TNF) and Receptor Activator of NFKB Ligand (RANKL)
CITED 21 TIMES as of July 2020.

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The Most Recent Publication from the Laboratory of Organic Chemistry of the National and Kapodistrian University of Athens in the Top 10% of the Most Downloaded Papers in the Highly Prestigious Journal “Angewandte Chemie International Edition”

On April 30th 2020, Wiley-VCH – European Chemical Society Publishing announced the top downloaded publications in recent publication history. The most recent publication from the Research Group of Assistant Professor Christoforos Kokotos is among the top 10% of the most downloaded papers in the highly prestigious scientific journal Angewandte Chemie International Edition (impact factor 12.24).

This study introduces a new chemical reaction for the synthesis of ketones from aldehydes and olefins via the development of a “green”, environment-friendly, organocatalytic (metal-free) photochemical organic transformation. For more details regarding the study, please read the following article link https://onlinelibrary.wiley.com/doi/abs/10.1002/anie.201912214 or http://www.chem.uoa.gr/?p=63347&lang=en

Two Recent Publications from the Laboratory of Organic Chemistry of NKUA in the Top 10% of the Most Downloaded Papers in the Journals “European Journal of Organic Chemistry” and “ChemCatChem”

On April 30th 2020, Wiley-VCH – European Chemical Society Publishing announced the top downloaded publications in recent publication history. Two publications from the Research Group of Assistant Professor Georgios C. Vougioukalakis are among the top 10% of the most downloaded papers in the scientific journals European Journal of Organic Chemistry and ChemCatChem.

 

Both publications are in the field of Organic Chemistry and Sustainable Catalysis. The first work is entitled “A Sustainable, User-Friendly Protocol for the Pd-Free Sonogashira Coupling Reaction” with authors Aggeliki A. Liori, Ioannis K. Stamatopoulos, Argyro T. Papastavrou, Afroditi Pinaka, and Georgios C. Vougioukalakis. It discusses the development of a new catalytic system for the palladium-free Sonogashira coupling reaction, based on a widely available, low-cost, non-toxic copper salt. The Sonogashira coupling reaction is widely utilized in industry and academia for the synthesis of compounds with important technological and biological applications. You can access this work by clicking: https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/ejoc.201800827

 

The second work is entitled “Unprecedented Multicomponent Organocatalytic Synthesis of Propargylic Esters via CO2 Activation” with authors Argyro T. Papastavrou, Martin Pauze, Enrique Gómez-Bengoa, and Georgios C. Vougioukalakis. It discusses an innovative, efficient, and straightforward organocatalytic method for the direct, multicomponent carboxylation of terminal alkynes with CO2 and organochlorides, towards propargylic esters, for the first time. Given that CO2 is the major greenhouse effect gas, its monetization towards the preparation of useful chemicals is of outmost importance, especially when this is achieved in a highly sustainable manner. This work can be accessed by clicking: https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/cctc.201900207

 

More information about these works and other research projects implemented in the Research Group of Assistant Professor Georgios C. Vougioukalakis can be found here: http://users.uoa.gr/~vougiouk

 

 

THE INTRODUCTION OF A NOVEL CHEMICAL REACTION FROM THE GROUP OF ASSISTANT PROFESSOR CHRISTOFOROS KOKOTOS OPENS NEW AVENUES FOR THE SYNTHESIS OF HIGH ADDED VALUE CHEMICALS

The development of a “green”, environment-friendly, organocatalytic (metal-free) photochemical organic transformation for the synthesis of ketones from the reaction between aldehydes and unactivated olefins was reported by the group of Assistant Professor Christoforos Kokotos. The publication entitled: «Green Metal-Free Photochemical Hydroacylation of Unactivated Olefins», which was carried out by PhD candidate Errika Voutyritsa and Assistant Professor Christoforos Kokotos in the Laboratory of Organic Chemistry of the Department of Chemistry of the National and Kapodistrian University of Athens, was published in the highly ranked international journal Angewandte Chemie. Angewandte Chemie, a journal of the Wiley publishing house, constitutes a top international journal in Chemistry with a high impact factor (12.24). Publication Link: https://onlinelibrary.wiley.com/doi/abs/10.1002/anie.201912214

The methodology describes a novel organic reaction that employs a small organic molecule (phenylglyoxylic acid) as the photoinitiator, water as the solvent and is carried out under very mild conditions by irradiation employing either household lamps or sunlight. The reaction constitutes a novel C-H activation methodology that does not require metal catalysts or directing groups and can be employed in a plethora of subtrates. The reaction and its products are of high importance for the Chemical Industry and especially the Pharmaceutical Industry. Key role in the success of the work was the study of the reaction mechanism in detail. This new synthetic methodology is expected to open new avenues in Organic Synthetic Chemistry and will find applications in the synthesis of high added value chemicals and pharmaceuticals, as well as in the synthesis of natural products.

Best Poster Award on Olive Oil study entitled “Potential of Ion Mobility combined with LC-HRMS in Food Authenticity Studies: Identification and Characterization of Secoiridoids Isomers found in Greek Extra Virgin Olive Oil”

Sofia Drakopoulou, a second-year PhD student, in the research group of Prof. Nikolaos Thomaidis, gained the award of Best Poster for her study on Olive Oil Authenticity, in the 9th Recent Advances in Food Analysis Symposium (RAFA 2019), conducted between 5th-8th of November in Prague, Czech Republic. The research study entitled “Potential of Ion Mobility combined with LC-HRMS in Food Authenticity Studies: Identification and Characterization of Secoiridoids Isomers found in Greek Extra Virgin Olive Oil” (Sofia K. Drakopoulou, Dimitrios E. Damalas, Carsten Baessmann, Nikolaos S. Thomaidis), has been included in the top 7 posters, awarded out of 500 posters participated in total.
Her research study focused on the identification and characterization of isomeric compounds found in olive oil, crucial in olive oil health claim. For the isomers separation, the cutting-edge technology of Trapped Ion Mobility combined to Q-TOF mass analyzer, introduced by Bruker, has been applied, while a novel structure elucidation workflow has also been proposed.
Her poster presented in the conference is part of her PhD research, which includes the development of advanced High-Resolution Mass Spectrometric methods for the thorough characterization of olive oil and discovery of new bioactive substances in food products of national importance and the substantiation of their authenticity.

Sofia Drakopoulou receives the best poster award during the closing ceremony of RAFA 2019

European Commission’s Innovation Radar Prize 2019 was awarded to a research project in which participates a research group from the Department of Chemistry of NKUA

The Innovation Radar is a European Commission initiative, which identifies high-potential innovations in EU-funded research and innovation projects. 36 of the best EU-funded innovators were identified to compete in four categories for the Innovation Radar Prize 2019.

The project LUMIBLAST: A paradigm shift in cancer therapy – using mitochondria-powered chemiluminescence to non-invasively treat inaccessible tumours, won the first prize in the category “Innovative Science 2019”.

LUMIBLAST aims at the development of a groundbreaking therapy, which will treat, in a non-invasive manner, difficult to reach tumors, such as glioblastoma multiforme (brain cancer). This therapeutic approach will use the energy produced from the mitochondria of the cancer cells to enable their self-fueled destruction. The goal of the NKUA research team is to design and synthesize the innovative molecules which will enable this therapy.

Besides the research team of the Department of Chemistry of NKUA, with Principal Investigator Assistant Professor Georgios C. Vougioukalakis, the other LUMIBLAST research groups come from Oslo University Hospital (PI: Prof. K. Berg), Universitat Politècnica de València (PI: Prof. M. Miranda), University of Oslo – School of Pharmacy (PI: Prof. H. H. Tønnesen) and Knight Scientific Limited from UK (PI: Dr. J. Knight). The LUMIBLAST concept has been submitted for intellectual property protection, in a patent application with co-inventors researchers from NKUA, Oslo University Hospital, and Universitat Politècnica de València.

For more information on LUMIBLAST, refer to the project’s webpage http://www.lumiblast.eu/ and the webpage of the research group of Assistant Professor Georgios C. Vougioukalakis http://users.uoa.gr/~vougiouk

Poster Award with title “Electronic Structure and Spectroscopy of Transition Metal Complexes”

Maria Drosou, a second-year PhD student in the group of Prof. Mitsopoulou, has been awarded a Physical Chemistry Chemical Physics Poster Prize at Summer School: ‘Electronic Structure and Spectroscopy of Transition Metal Complexes’, which held from 29 September – 4 October 2019 at Gelsenkirchen, Germany and was attended by 80 young researchers. The summer school was jointly organized by Prof. Frank Neese Dr. Serena DeBeer and Dr D. Pantazis working at the Mülheim Max-Planck Institutes (MPI für Chemische Energiekonversion and MPI für Kohlenforschung) (https://summerschool.cec.mpg.de/index.php?id=1202). It was also supported by the the Editorial Board of Physical Chemistry Chemical Physics (PCCP) of the Royal Society of Chemistry.

The summer school focused particularly on how the combination of spectroscopic techniques with quantum chemistry and high-level computation is used in transition metal chemistry. This combination is a fundamental component of modern molecular sciences since it drives cutting-edge research in fields ranging from inorganic chemistry to biochemistry and from catalysis to energy research.

Her Poster titled: ‘DFT Studies on the Mechanism of Hydrogen Evolution Catalyzed by Nickel Thiolates’ (M. Drosou, A. Zarkadoulas, F. Kamatsos, C. A. Mitsopoulou), and is part of her PhD research, which includes DFT and ab initio calculations for elucidating the mechanism of HER with catalysts of non- noble and abundant metal complexes in photocatalysis and elecrocatalysis.