Institute of Chemical Biology - National Hellenic Research Foundation

Synthetic Medicinal Chemistry and Chemical Biology
Dr. Kyriakos C. Prousis | Senior Researcher, Group Leader

About Team Collaborations Funding Publications

erc_logo The K. C. Prousis group is focused on activities combining the fields of Synthetic Medicinal Chemistry and Chemical Biology. The group aims to provide new therapeutic approaches against several lethal diseases with high socioeconomic impact including Cancer, Inflammation, Antibacterials, Neurodegenerative Diseases and Parasitic Neglected Diseases.

The activities of the group follow two major research lines:

Design and synthesis of biologically active, small organic molecules towards the identification of new lead compounds for the prevention and treatment of diseases of our interest.
Design and synthesis of new strategic NIR fluorescence ‘smart probes’, suitable for Optical Imaging and Biomedical applications related to Cancer and Neurodegenerative Diseases. The use of these ‘smart probes’ will support early diagnosis and therapy, in a non-invasive manner and will provide the opportunity of Theranostic applications.

Research Activities Overview

Combating Cancerous Malignancies

Cancer as a condition refers in abnormal and uncontrolled cell growth across any organ or tissue of the body, remaining still unaddressed until today with treatment issues like general toxicity, side effects, relapse and emerging drug resistance. Appearance and progression of the disease are based on complex and multifactorial etiologies. Among the most important proteins recognized and implicated in numerous cancer hallmarks & inflammatory processes are Galectins. This family of proteins showcases cancer specific functions and their abundant expression in such malignant conditions makes them appealing targets for inhibition or modulation giving space for the development of novel cancer treatments.

Inflammation & Cancer

The existing coherence among cancer and inflammation has been really old and dates back to the late 19th century, where scientists hypothesized that cancer appears where the immunoresponse cells are invading existing inflamed sites. Until today the mechanism is not clearly known but they share common pathways like proliferation, migration, angiogenesis and cell survival. Although inflammation possess a normal immunoresponse to endogenous or exogenous stimuli, chronic inflammation is associated with elevated risk for several diseases occurrence. Moreover, cancer cells show high plasticity in contrast to cancer-associated inflammatory cells that are genetically stable and strategically this could be exploited to circumvent emerging drug resistant cancers.

Cancer Theranostics

The emerging field of ‘Cancer Theranostics’, arises as a cutting-edge approach offering a valuable combination of cancer diagnosis and therapy, aiming to provide early diagnosis, more accurate molecular imaging and precise treatment options. The necessity for accurate diagnosis and treatment at the right time, could be served as a promising and successful modality to alleviate the development and progress of cancer, in a way to improve the survival rate and subsequently the quality of patients lives. Until today, numerous Theranostic probes have been developed and already established as tools for cancer precision and personalized medicine. Therefore, the need for further development of innovative theranostic ‘smart’ probes still remains an urgent topic.

Combating Bacterial Resistance

The emergence of resistant pathogens to antibacterial drugs is becoming one of the most serious threats of the future global health. This became even more apparent the past two years of the pandemic with the witnessed wave of increasing pressure to national health systems. Hence, rising resistance of pathogens to currently available therapies exhibits a consecutive decline of successful infection treatments. The research interest on identifying novel bacterial targets in order to combat resistant strains is continuous and several promising targets have been identified so far. Amongst them are factors directly implicated in bacterial cell divisions that show great interest, given the fact they are highly conserved and posses potent antibacterial activity over drug resistant pathogens.

Group Structure and Personnel

Dr. Kyriakos C. Prousis, Senior Researcher, Group Leader

G. Nigianni, PhD Candidate
E. Konstanteli, PhD Candidate

Collaborations

National

Research Director T. Calogeropoulou, ICB-NHRF
Research Director D. Papahatjis, ICB-NHRF
Research Director M. Koufaki, ICB-NHRF
Senior Researcher V. Pletsa ICB-NHRF
Senior Researcher P. Georgiadis ICB-NHRF
Professor V. Roussis, Pharmacy Department, University of Athens - UOA
Professor A. Gravanis, Medical School, University of Crete - UOC
Professor A. Detsi, Department of Chemical Engineering, National Technical University of Athens - NTUA
Associate Professor E. Ioannou, Pharmacy Department, University of Athens - UOA
Associate Professor Ioannis Charalampopoulos, Foundation for Research and Technology Hellas - FORTH
Associate Researcher A. Kaltzoglou, TPCI-NHRF

International

Professor J. Z. Torres, Department of Chemistry and Biochemistry, University of California Los Angeles - UCLA
Professor M.-P. Costi, Pharmacy Department, University of Modena and Reggio Emilia, Italy
Dr A. Cordeiro-da-Silva, Instituto de Biologia Molecular e Celular, Porto, Portugal
Professor Dame Pamela Shaw, University of Sheffield, Sheffield Institute for Translational Neuroscience, United Kingdom
Professor S. Mangani, University of Siena, Italy
Professor Rebecca Wade, HITS gGmbH, Molecular and Cellular Modeling Group, Germany
Professor Christophe Rochais, Université de Caen Normandie, France
Dr. Vasileia-Ismini Alexaki, Technische Universität Dresden, Faculty of Medicine, Germany
Dr. Marie-Ann Ewart, AvantiCell Science Ltd., United Kingdom
Associate Professor Ka Wan Li, Stichting VU, Department of Molecular and Cellular Neurobiology, The Netherlands

Collaborations with Companies

Novartis (Hellas) S.A.C.I., Greece
Accelopment AG, Switzerland

Funding

European

H2020-MSCA-ITN-2017, EuroNeurotrophin: ‘A European training network for the discovery of neurotrophins small molecule mimetics as potential therapeutic agents for neurodegeneration and neuroinflammation’.

National

GSRT Infrastructures program, Bioimaging–GR: ‘A Greek Research Infrastructure for Visualizing and Monitoring Fundamental Biological Processes’

Selected Publications

“Development and biological characterization of a novel selective trka agonist with neuroprotective properties against amyloid toxicity”, Rogdakis T., Charou D., Latorrata A., Papadimitriou E., Tsengenes A., Athanasiou C., Papadopoulou M., Chalikiopoulou C., Katsila T., Ramos I., Prousis K. C., Wade, R. C., Sidiropoulou, K., Calogeropoulou, T., Gravanis, A., Charalampopoulos, I., Biomedicines, 2022, 10(3), 614
DOI: https://doi.org/10.3390/biomedicines10030614
“A novel synthetic protocol for the synthesis of pulvinones, and naturally occurring Aspulvinone E, molecules of medicinal interest”, Prousis, K.C.*, Katsamakas, S., Markopoulos, J., Igglessi-Markopoulou, O. Synthetic Communications, 2022, 52(1), 117 – 128
DOI: https://doi.org/10.1080/00397911.2021.2001662
“Design, Synthesis and Antiparasitic Evaluation of Click Phospholipids”, G.E. Magoulas, P. Afroudakis, K. Georgikopoulou, M. Roussaki, C. Borsari, T. Fotopoulou, N. Santarem, E. Barrias, P. T. Nevado, J. Hachenberg, E. Bifeld, B. Ellinger, M. Kuzikov, I. Fragiadaki , E. Scoulica, J. Clos, S. Gul, M.P. Costi, W. de Souza, K.C. Prousis, A. Cordeiro da Silva, T. Calogeropoulou, Molecules 2021, 26(14), 4204
DOI: https://doi.org/10.3390/molecules26144204
“Synthesis, biological evaluation and QSAR studies of new thieno[2,3-d]pyrimidin-4(3H)-one derivatives as antimicrobial and antifungal agents”, G.E. Magoulas, L. Kalopetridou, A. Ćirić, E. Kritsi, P. Kouka, P. Zoumpoulakis, N. Chondrogianni, M. Sokovic, K.C. Prousis, T. Calogeropoulou, Bioorg. Chem. 2021, 106, 104509
DOI: https://doi.org/10.2174/1381612826666201210115340
“New cationic heptamethinecyanine-graphene hybrid materials”, K.C. Prousis, Ruben Canton-Vitoria, Georgia Pagona, Maria Goulielmaki, Vassilis Zoumpourlis, Nikos Tagmatarchis, Theodora Calogeropoulou, Dyes and Pigments 2020, 175, 108047
DOI: https://doi.org/10.1016/j.dyepig.2019.108047
“Functional characterization and anti-cancer action of the clinical phase II cardiac Na+/K+ ATPase inhibitor istaroxime: in vitro and in vivo properties and cross talk with the membrane androgen receptor” K. Alevizopoulos, K. Dimas, N. Papadopoulou, E.-M. Schmidt, A. Tsapara, S. Alkahtani, S. Honisch, K. C. Prousis, S. Alarifi, T. Calogeropoulou, F. Lang, C. Stournaras; Ongotarget 2016, 7, 17, 24415 – 28.
“Selective and differential interactions of BNN27, a novel C17-spiroepoxy steroid derivative, with TrkA receptors, regulating neuronal survival and differentiation” I. Pediaditakis, P. Efstathopoulos, K. C. Prousis, M. Zervou, J. C. Arévalo, V. I. Alexaki, V. Nikoletopoulou, E. Karagianni, C. Potamitis, N. Tavernarakis, T. Chavakis, A. N. Margioris, M. Venihaki, T. Calogeropoulou, I. Charalampopoulos, A. Gravanis; Neuropharmacology 2016, 111, 266–282.
DOI: https://doi.org/10.1016/j.neuropharm.2016.09.007
“Identification of Novel Chemical Scaffolds Inhibiting Trypanothione Synthetase from Pathogenic Trypanosomatids” D. Benítez, A. Medeiros, L. Fiestas, E. A. P. Zenere, F. Maiwald, K. C. Prousis, M. Roussaki, T. Calogeropoulou, A. Detsi, T. Jaeger, J. Šarlauskas, L. P. Mašič, C. Kunick, G. R. Labadie, L. Flohé, M. A. Comini; PLOS Neglected Tropical Diseases 2016, 10(4): e0004617.
“An efficient synthetic approach towards fully functionalized tetronic acids: the use of 1,3-dioxolane-2,4-diones as novel protected-activated synthons of a-hydroxy acids” K. C. Prousis, John Markopoulos, Vickie Mckee, Olga Igglessi-Markopoulou;; Tetrahedron 2015, 66, 8637-48.
“Design and synthesis of 21-alkynylaryl pregnenolone derivatives and evaluation of their anticancer activity”G. Szalóki, A. Pantzou, K. C. Prousis, O. Mavrofrydi, P. Papazafiri, T. Calogeropoulou; Bioorg. & Med. Chem. 2014, 22, 6980–6988.
“Steroidal Cardiac Na+/K+ ATPase Inhibitors Exhibit Strong Anti-Cancer Potential in Vitro and in Prostate and Lung Cancer Xenografts in Vivo” K. Dimas, N. Papadopoulou, C. Baskakis, K. C. Prousis, M. Tsakos, S. Alkahtani, S. Honisch, F. Lang, T. Calogeropoulou, K. Alevizopoulos, C. Stournaras; Anticancer Agents Med Chem 2014, 14(5), 762 – 770.
DOI: http://dx.doi.org/10.2174/18715206113136660338
“Effect of alkylphospholipids on Candida albicans biofilm formation and maturation” T. V. M. Vila, K. Ishida, W. de Souza, K. C. Prousis, T. Calogeropoulou, S. Rozental; J. Antimicrobial Chemotherapy 2013, 68(1) 113-125.
“Efficient Efficient construction of functionalized 5-Carboxymethyl Tetramic Acids using N-Ac-L-aspartic Anhydride as Chiral Building Block” K. C. Prousis, J. Markopoulos, V. Mckee, O. Igglessi-Markopoulou; Tetrahedron, 2010, 66, 3944-3950.
“Design and Synthesis of Novel Quinolinone-3-aminocarboxamides and their α-Lipoic Acid Adducts as Antioxidant and Antiiflammatory Agents.” A. Detsi, D. Bouloumbasi, K. C. Prousis, M. koufaki, G. Athanasellis, G. Melagraki, A. Afantitis, O. Igglessi-Markopoulou, C. Kontogiorgis, D. Hadjipavlou-Litina; J. Med. Chem. 2007, 50, 2450-2458.

Patents

BIOINSPIRED PROTEASOME ACTIVATORS WITH ANTIAGING ACTIVITY”, GR20180100094A, WO2019171088A1, Inventors: Koufaki Μ., Calogeropoulou T., Chondrogianni Ν., Papahatjis D., Gonos E., Fotopoulou T., Prousis Κ. C., Chazapi Ε.
“COMPOUND FOR USE IN THE TREATMENT OF PROTOZOAL DISEASES AND PROCESS FOR PRODUCTION OF SAID COMPOUND”. Greek Patent Application No. 20200100577, Inventors: Theodora Calogeropoulou, Kyriakos C. Prousis, Marina Roussaki, George Magoulas, Theano Fotopoulou.