INSTITUTE OF CHEMICAL BIOLOGY
 
  Drug Discovery
  Molecular Analysis
  Organic and Organometallic Chemistry
  Medicinal Chemistry
  Synthetic and Medicinal Chemistry
  Synthetic Medicinal Chemistry and Chemical Biology
  Identification & validation of novel therapeutic targets - Biological evaluation of bioactive small molecules and drugs
  Structural Biology & Chemistry
  Cryogenic electronic microscopy (Cryo-EM) with emphasis on study of proteins, of their interactions and of subcellular particles
  Molecular Endocrinology
  Signal Mediated Gene Expression
  Molecular & Cellular Ageing
  Biomedical Applications
  Holistic Approaches in Health
  Environment and Health
  Metabolic Engineering-Bioinformatics
  Biomarker Discovery & Translational Research
  Bioinformatics focusing on the development of new methodologies and tools
  Biotechnology
  Enzyme and Synthetic Biotechnology
  Biomimetics & Nanobiotechnology
  Conjugated Polymers for Healthcare, Bioelectronics and Bioimaging

 

Medicinal Chemistry - Drug Discovery
Dr. Demetris Papahatjis | Research Director, Group Leader

 

The Group focuses on the design and synthesis of new bioactive compounds for the prevention and treatment of diseases including cancer, neurodegenerative diseases and aging. A parallel research activity involves the development of synthetic methodology.

Research interests are focused on the design and synthesis of bioactive heterocyclic molecules.
In particular:

a) Benzothiophene/hydroxytyrosol hybrids and bioisosteres as proteasome activators, against ageing and age related diseases.

b) Design and synthesis of (13S)-Methyl-Substituted Arachidonic Acid Analogues: Templates for Novel Endocannabinoids.

c) Design and synthesis of novel cannabinoid analogues. Probing the cannabinoid subsite  at C1΄ and C1΄-C2΄ of the side chain.

d) New BRAFV600E inhibitors for the development of agents against colorectal cancer. Novel benzothiophene analogues were designed and synthesized as potential inhibitors of KRAS and/or BRAF mutant colorectal cancer (CRC).

 

Ongoing Research Activities

Discovery of a new class of bioinspired antiaging and neuroprotective proteasome activators

Although the research towards the development of small molecules as proteasome activators is scarce, the results so far suggest that activation of the proteasome complex constitutes a pioneer strategy for the deceleration of ageing and age-related diseases A novel class of hybrid compounds that combine structural features of benzothiophene and of hydroxytyrosol connected through carefully selected linkers, was designed and synthesized by our group, leading to the development of an optimum structural proteasome activator.

STHENOS-b 2017-2020 in collaboration with members of other research groups of I.C.B.

This class of compounds was further exploited by synthesizing more analogues. The biological results to date show great promise with regards to the anti-ageing and neuroprotective effects of the new analogues in cellulo and in organismal level.

RESET: “Bio-inspired antiaging proteasome activators” In collaboration with Intermed SA.

Design and synthesis of (13S)-Methyl-Substituted Arachidonic Acid Analogues: Templates for Novel Endocannabinoids

By the mid 1990’s, the first two key endocannabinoids N-arachidonoylethanolamine ("anandamide") (AEA, Ia) and 2-arachidonoyl glycerol (2-AG, Ib) were isolated and characterized as derivatives of the non-cannabinergic, arachidonic acid (AA, Ic). AEA and 2-AG act at CB1 and CB2, the two known Gi/o-protein-coupled cannabinoid receptors (CBs), to modulate physiological and pathological processes including nociception, inflammation, neuroprotection, feeding, memory, anxiety  and cell proliferation. The biological actions of AEA and 2-AG are terminated by a transport mechanism and enzymatic deactivation. In most tissues, AEA is metabolized hydrolytically by fatty acid amide hydrolase (FAAH), and 2-AG by monoacylglycerol lipase (MAGL).

imageRecently from our laboratory we reported the design, synthesis, and preliminary biological data of two novel endocannabinoid molecular probes referred to as "(13S)-methyl substituted anandamide analogs". It is especially worthy of note that (13S)-methyl substituted anandamide is among the endocannabinoid analogs with the highest CB1-binding affinity known to date.

Subsequently, the most promising analogues were modified at the polar head and tail groups to further probe CB receptor recognition in tandem with increasing the stability of the amide group for FAAH. Our design approaches led to a chiral arachidonoyl ethanolamide (AEA) analogue, namely,

(R)-N-(1-Methyl-2-hydroxyethyl)-13-(S)-methyl-arachidonamide (AMG315):

We reported the first AEA probe, namely (13S,1′R)-dimethyl-anandamide [(13S,1′R)-di-Me-AEA], possessing high affinity and potency for the cannabinoid CB1 receptor coupled with excellent biochemical stability for FAAH, MGL, ABHD6, and COX-2. When tested in vivo using the CFA-induced inflammatory pain model, behaved as a more potent analgesic when compared to endogenous AEA. This novel analogue will serve as a very useful endocannabinoid probe.

Design and synthesis of novel cannabinoid analogues. Probing the cannabinoid subsite at C1΄ and C1΄-C2΄

imageOur laboratory has pioneered in the design and use of “cannabinoid ligands” as tools for studying the binding domain of the different classes of ligands within the CB1 and CB2 receptors. Earlier work from our laboratory has revealed a strong correlation between the presence of substituents at C1¢-position of (-)-D8-tetrahydrocannabinols ((-)-D8-THCs,) and the existence of a subsite within the CB1 and CB2 cannabinoid receptor binding domain.

We have expanded the group of cyclic C1′-substituents to include: a) the previously unexplored respective gem-dihalocyclopropyl analogs, and explore the pharmacophoric limits of side chain length and the effects of conformational restriction at the C2-C5′as depicted in Fig. 1. and b) since all four diastereomers of 1΄,2΄-dimethylheptyl-Δ8-THC have been synthesized and proved to be quite potent we have synthesized C-1΄-C-2΄ constrained cannabinoid analogues bearing heterocyclic rings, by incorporating modern synthetic methods. The novel analogs can provide additional insight into the stereo-electronic requirements for interaction with CB receptors, and aid in the discovery of more potent and selective drug candidates.

 

 

Group Structure and Personnel

Dr. Demetris Papahatjis, Research Director, Group Leader

 

Group members (2018 to present)

  • Ms Dafni Chandrinou MSc. (matching funds-Arcade)
  • Ms Olga Kirkilesi MSc. (Bioimaging)
  • Dr Theano Fotopoulou Projects: (Sthenos b and RESET)
  • Dr Sotirios Katsamakas (RESET)
  • Dr Michail Mamais (Sthenos b and Opensreen)
  • Dr George Magoulas (Sthenos b)
  • Dr Alia Cristina Tenchiu (Sthenos b)

 

 

 

Collaborations

The group collaborates with the other medicinal chemists of ICB and also with the groups of molecular analysis, molecular and cellular ageing, signal mediated gene expression and biomarker discovery and translational research, through the participation in common grant applications and publications. 

 

 

Funding

  • Research, Create, Innovate MIS 5031214 (2018-2022) Project RESET: “Bio-inspired antiaging proteasome activators”
  • Research Funding Program (2018-2021) BioImaging-GR “A Greek Research Infrastructure for Visualizing and Monitoring Fundamental Biological Processes”
  • Research Funding Program MIS 5002691 (2018-2021) OPENSCREEN-GR: “An open-access research infrastructure of target-based screening technologies and chemical biology for human and animal health, agriculture and the environment”
  • Research Funding Program KRIPIS2: (2017-2020) Project STHENOS-B: "Targeted therapeutic approaches against ageing and degenerative diseases, cancer in particular - Hit compounds optimization"
  • Research Funding Program KRIPIS: (2013-2015) Project STHENOS: "Targeted therapeutic approaches against ageing and degenerative diseases, cancer in particular”
  • REGPOT-2009-1/ARCADE 245866 (2010-2013) “Advancement of Research Capability for the Development of New Functional Compounds” 
  • Professional Services Agreements with Northeastern University on behalf of its Center for Drug Discovery. (2008-2010). "a) Multistep synthesis of bicyclic and tricyclic cannabinoids. b) Synthesis of inhibitors of FAAH and/or MGL.
  • Professional Services Agreements with UNI-PHARMA. S.A. (2011-2012).
  • EU Marie Curie Early Stage Training (EST) (2006-2010) “A European Research Training Site for the Design and Synthesis of Novel Neuroprotective and Hypoglycaemic Agents through a Multi-disciplinary approach”
  • Operational Programme for Competitiveness, GSRT YB/60 (2004-2007) “Exploitation of novel cannabinoid analogs with possible analgesic, psychomotor and anti-abuse potential”
  • GSRT programme Location and use of research results by the creation of new enterprises (Spin-off, 2003-2005) “Cannabinomimetic analogs with therapeutic applications”
  • Excellence in the Research Institutes (2002-05) "Novel strategies against neurodegeneration"

 

 

Publications

  • “Total Synthesis of Ionophore Antibiotic X-14547A.  1. Enantion-selective Synthesis of the Tetrahydropyran and Tetrahydroindan Building Blocks”, K.C. Nicolaou, D.P. Papahatjis, D.A. Claremon And R.E. Dolle, III, J. Am. Chem. Soc., 103, 6967-6969 (1981).
  • “Total Synthesis of Ionophore Antibiotix X-14547A. 2. Coupling of the Tetrahydropyran and Tetrahydroindan Systems and Construction of the Butadienyl and Ketopyrrole Moieties”, K.C. Nicolaou, D.A. Claremon, D.P.  Papahatjis and R.L. Magolda, J. Am. Chem. Soc., 103, 6969-6971 (1981).
  • “A Mild Method for the Synthesis of 2-Ketopyrroles from Carboxylic Acids”, K.C. Nicolaou, D.A. Claremon and D.P. Papahatjis, Tetrahedron Letters, 22 (46) 4647-4650 (1981).
  • “A New, Mild and general Method for the Synthesis of 0-glycosides”, K.C. Nicolaou, S.P. Seitz and D.P. Papahatjis, J. Am. Chem. Soc., 105, 2430 (1983).
  • “Practical Synthesis of Oligasaccharides, Partial Synthesis of Avermectin B1a”, K.C. Nicolaou, R.E. Dolle, D.P. Papahatjis and J.L. Randall, J. Am. Chem. Soc., 106. 4189 (1984).
  • “Total Synthesis of Ionophore Antiobiotix X-14547A”, K.C. Nicolaou, D.P. Papahatjis, D.A. Claremon, R.L. Magolda and R.E. Dolle, J. Org. Chem., 50, 1440 (1985).
  • “Modern Synthetic Technology and Total Synthesis of Bioactive Molecules”, K.C. Nicolaou, N.A. Petasis, R.E. Dolle, S.W. Li, D.P. Papahatjis,  J. Uenishi, R.E. Zipkin, in “New Methods in Drug Research”, A. Makriyannis, Ed., J.R. Prous Science, Barcelona, Ch. 11, pp. 179-200, (1985).
  • “Ionophore Antibiotix X-14547A.  Enantioselective Synthesis of the Tetrahydropyrran  Unit.  Studies towards the Synthesis of Amphotericin B.  Syntheis of O-Glycosides and Glycosyl fluorieds”, D.P. Papahatjis, Ph.D. Thesis, University of Pennysylvania (Supervisor: Prof. K.C. Nicolaou), 1984, 336 pp.
  • “Sterocontrol Construction of Key Building Blocks for the Total Synthesis of Amphoteronolide B and Amphotericin B”,  K.C. Nikolaou, R.A. Daines, J. Uenishi, W.S. Li, D.P. Papahatjis and T.K. Chakraborty, J. Am. Chem. Soc., 109, 2205 (1987).
  •  “Total Synthesis of Amphoteronolide B and Amphotericin B”.  1. Strategy and Stereocontrolled Construction of Key Building Blocks, K.C. Nicolaou, R.A. Daines, J. Uenishi, W.S. Li, D.P. Papahatjis, and T.K. Chakraborty,  J. Am. Chem. Soc., 110, 4672 (1988).
  • “Enhanced Optical Purity of 3-Hydroxy-esters Obtained by Bayker’s Yeast Reduction of 3-Ketoesters”, V. Spiliotis,  D.P. Papahatjis and N. Ragoussis, Tetrahedron Letters, 31, (11) 1615-1616 (1990).
  • “A brief review of the recent achievements in the field of Cannabinoids with main emphasis on the synthesis of lead compounds and their interactions on lipid bilayers”, T. Mavromoustakos, D.P. Papahatjis, T. Kourouli, E. Theodoropoulou, A. Makriyannis, Rev. Clinical Pharmacology, 13, 105 (1995).
  • “Study of Thermotropic properties of Cannabinoids inPhosphatidylcholine bilayers using Diffferential scanning Calorimetry and Small Angle X-ray Diffaction”, T. Mavromoustakos, D.P. Papahatjis, E. Theodoropoulou, T. Kourouli, De-Ping Yang, M. Trumbore, A. Makriyannis, Biochim. Biophys. Acta, 1281, (2) 235-244 (1996).
  • “Pharmacophoric Requirements for Cannabinoid Side chains.  Naphthoyl and Naphthylmethyl asubstituted Δ8-THC Analogs.”, D.P.Papahatjis, T. Kourouli and A. Makriyannis, J. Heter. Chem. 33, 559-562 (1996).
  • “Pharmacophoric Requirements for Cannabinoid Side Chains. Multiple bond and C1’ –Substituted Δ8-Tetrahydrocannabinols”, D.P. Papahatjis, T. Kourouli, V. Abadji, A. Goutopoulos and A. Makriyannis, J. Med. Chem. 41, 1195 (1998).
  • “Novel Analogues of Arachidonylethanolamide (Anandamide): Affinities for the CB1 and CB2 Cannabinoid Receptors and Metabolic Stability.” S. Lin, A. T. Khanolkar, P. Fan, A. Goutopoulos, Ce Qin, D.P. Papahatjis, and A. Makriyannis, J. Med. Chem. 41, 5353 (1998).
  • “Structure Elucidation and Conformational Properties of Synthetic Cannabinoids 2-[6a,7,10,10a-tetrahydro-6,6,9-trimethyl-6H dibenzo [b,d]pyran-1-ol]-2-[hexyl]-1,3-dithiolane and its methylated analog” T. Mavromoustakos, E. Theodoropoulou, M. Zervou, T. Kourouli and D.P. Papahatjis.  J. Pharm. Biomed. Analysis.18, 947 (1999).
  • “A New Ring-Forming Methodology for the Synthesis of Conformationally Constrained Bioactive Molecules” Demetris P. Papahatjis, Spyros Nikas, Andrew Tsotinis, Margarita Vlachou and Alexandros Makriyannis. Chemistry Letters 3, 192 (2001).
  • “Differential membrane fluidization by active and inactive cannabinoid analogs” T. Mavromoustakos, D.P. Papahatjis, P. Laggner.Biochimica et Biophysica Acta  1512, 183 (2001).
  • “Novel 1’,1’-Chain Substituted  D8-Tetrahydrocannabinols” Demetris P. Papahatjis , Spyros P. Nikas,  Thanos Andreou and Alexandros Makriyannis. Biorganic and Medicinal Chemistry Letters. 3583, (2002).
  • “Pharmacophoric Requirements for Cannabinoid Side Chains. 3: Probing the Cannabinoid Receptor subsite at C1΄”Demetris P. Papahatjis , Spyros P. Nikas, Therapia Kourouli, Ravi Chari, Wei Xu, Roger G. Pertwee and Alexandros Makriyannis.   J. Med. Chem. 46, 3221, (2003)
  • “The Role of Halogen Substitution in Classical Cannabinoids. A CB1 Pharmacophore Model.” Spyros P. Nikas, Jolanta Grzybovska, Demetris P. Papahatjis, Avgui Charalambous, Ali R. Banijamali, Ravi Chari, Pusheng Fan, Therapia Kourouli, Sonyuan Lin, Albert J. Nitowski, Gilbert Marciniak, Yan Guo, Xiuyan Li, Chia-Lin J. Wang and Alexandros Makriyannis. AAPS, Journal. 6(4): Article 30 (2004)
  • “Preclinical behavioral evaluation of a novel cannabinoid analogue” Antoniou K, Galanopoulos A, Vlachou S, Nahmias V, Thermos, K, Panagis G, Daifoti Z, Marselos M., Papahatjis D, and Spyraki C. Rev. Clinical Pharmacology and Pharmacokinetics, 23, 26 (2005).
  • “Behavioral pharmacological properties of a novel cannabinoid 1’,1’-dithiolane  Δ8-THC analogue,  AMG-3.” Antoniou K, Galanopoulos A, Vlachou S, Kourouli T, Nahmias V, Thermos, K, Panagis G, Daifoti Z, Marselos M., Papahatjis D, and Spyraki C. Behavioral Pharmacology. 16, 499 (2005).
  • “ A Convenient Preparation of Enantiomerically Pure Esters of trans-Epoxysuccinic Acid” D.P. Papahatjis, T. Kourouli, Victoria Nahmias. Letters in Organic Chemistry, 3, 45 (2006).
  • “Structural Modifications of the Cannabinoid Side Chain towards C3-Aryl and 1΄,1΄-Cycloalkyl-1΄-Cyano Cannabinoids” Demetris P. Papahatjis, Victoria R. Nahmias, Thanos Andreou, Pusheng Fan, and Alexandros Makriyannis. Biorganic and Medicinal Chemistry Letters. 1616, (2006).
  • “Mapping the Melatonin Receptor. 7. 8-Substituted  N-Acyl-5-methoxytryptamines and 8-substituted N-Acyl-5-methoxy-1-methyltryptamines: N-butanoyl 5-methoxy-1-methyl-8,8-trimethylenetryptamine (12c), a human MT2 agonist that is an antagonist at the human MT1 receptor. Andrew Tsotinis, Margarita Vlachou, Demetris P. Papahatjis, Theodora Calogeropoulou, Spyros Nikas, Peter J. Garratt, Vincent Piccio, Stefan Vonhoff Kathryn Davidson, Muy-Teck Teh and David Sugden. J. Med. Chem. 49, 3509, (2006).
  • “Pharmacological characterization of novel ligands for CB1 and CB2 cannabinoid receptors” Thermos K, Papazoglou M, Antoniou K, Mastrodimou N, Panagis G, Vlachou S, Renieri E, Nahmias V, Menissiou A, Gianni M, Kondylis MP, Daifoti-Papadopoulou Z, Papahatjis D, Spyraki C Acta Pharmacological Sinica,  27: 394-395 Suppl. 1, Jul (2006).
  • “An Efficient Synthesis of Simple β,β'-Cyclobisalkylated Melatoninergic Phenylalkylamides” Andrew Tsotinis, Margarita Vlachou,  Demetris P. Papahatjis, Spyros P. Nikas and David Sugden. Letters in Organic Chemistry, 4, 92 (2007).
  • “The C1´-Cycloalkyl Side Chain Pharmacophore in Tetrahydrocannabinols”. Demetris P. Papahatjis, Victoria R. Nahmias, Spyros P. Nikas, Thanos Andreou, Shakiru O. Alapafuja, Andrew Tsotinis, Jianxin Guo, Pusheng Fan, and Alexandros Makriyannis. J. Med. Chem. 50, 4048, (2007).
  • “The Applications of 3D-QSAR Studies for Novel Cannabinoid Ligands Substituted at the C1΄ Position of the Alkyl Side Chain on the Structural Requirements for Binding to CB1 and CB2 Receptors” Serdar Durdagi, Agnes Kapou, Therapia Kourouli, Thanos Andreou,  Spyros P. Nikas,  Victoria R. Nahmias,  Demetris P. Papahatjis,  Manthos. G. Papadopoulos and Thomas Mavromoustakos. J. Med. Chem. 50, 2875, (2007).
  • “Cannabilactones: A Novel Class of CB2 Selective Agonists with Peripheral Analgesic Activity” Atmaram D. Khanolkar, Dai Lu, T. Philip Malan, Jr., Mohab Ibrahim, Frank Porreca, Ganesh A. Thakur, Vijayabaskar Veerappan, Richard I. Duclos, Jr.,  Xiaoyu Tian, Clifford George, Damon A. Parrish, Demetris Papahatjis and Alexandros Makriyannis. J. Med. Chem. 50, 6493, (2007).
  • “Combined 3D QSAR and molecular docking studies to reveal novel cannabinoid ligands with optimum binding activity”   Durdagi, S., Papadopoulos, M.G., Papahatjis, D.P., Mavromoustakos, T. Biorganic and Medicinal Chemistry Letters. 6754, (2007).
  • “Novel ligands for cannabinoid receptors: Pharmacological studies” Antoniou K, Chouliara, O, Polissidis, A, Papalexi, E. Papazoglou M, Mastrodimou N, Panagis G, Vlachou S, Renieri E, Nahmias V, Menissiou A, Gianni M, Kondylis MP, Thermos K., Daifoti-Papadopoulou Z, Papahatjis D, Spyraki C. Behavioral Pharmacology. 18, supp.1, 24 (2007).
  • “Testing the 3D QSAR/ComFA-CoMSIA results of flexible bioactive compounds  with molecular docking studies” Serdar Durdagi, Catherine Koukoulitsa, Agnes Kapou,  Therapia Kourouli,   Thanos Andreou,  Spyros P. Nikas,  Victoria R. Nahmias,  Demetris P. Papahatjis,  Manthos. G. Papadopoulos and Thomas Mavromoustakos. Drugs of the Future, 32, supp A, 79 (2007).
  • “Putative Bioactive Conformers of Small Molecules: A Concerted Approach using NMR Spectroscopy and Computational Chemistry” T. Mavromoustakos, S. Golic Grdadolnik, M. Zervou, P. Zoumpoulakis, C. Potamitis, A. Politi, E. Mantzourani, J.A. Platts, C. Koukoulitsa, P. Minakakis, G. Kokotos, T. Tselios, J. Matsoukas, S. Durdagi, M. G. Papadopoulos, D. P. Papahatjis, Z. Spyranti, G.A. Dalkas, G.A. Spyroulias, In: Medicinal Chemistry Research Progress, G.P. Colombo and S. Ricci (Eds.), (2008), Nova Science Publishers, Inc.
  • “Design and Synthesis of (13S)-Methyl Substituted Arachidonic Acid Analogs: Templates for Novel Endocannabinoids” Demetris P. Papahatjis, Victoria R. Nahmias, Spyros P. Nikas, Marion Schimpgen, Alexandros Makriyannis.  CHEMISTRY - A European Journal. 16/13, 4091, (2010).
  • “Novel 1′-1′ Chain Substituted Hexahydrocannabinols: 9β-Hydroxy-3-(1-hexyl-cyclobut-1-yl)-hexahydrocannabinol (AM2389) a Highly Potent Cannabinoid Receptor 1 (CB1) Agonist”. Spyros P. Nikas, Shakiru O. Alapafuja, Ioannis Papanastasiou, Carol A. Paronis, Vidyanand G. Shukla, Demetris P. Papahatjis, Anna L. Bowman, Aneetha Halikhedkar, Xiuwen Han, and Alexandros Makriyannis. J. Med. Chem. 53, 6996–7010, (2010).
  • “The cannabinoid CB1 receptor biphasically modulates motor activity and regulates dopamine and glutamate region dependently”. Alexia Polissidis, Andreas Galanopoulos, George Naxakis, Demetris Papahatjis, Zeta Papadopoulou-Daifoti, Katerina Antoniou. Int. J. of Neuropsychopharmacol. 16 (2), 393-403, (2013).
  • “Cannabinoids Negatively Modulate Striatal Glutamate and Dopamine Release and Behavioural Output of Acute D-Amphetamine”. Polissidis, A.; Chouliara, O.; Galanopoulos, A.; Naxakis, G.; Papahatjis, D.; Papadopoulou-Daifoti, Z.; Antoniou, K. Behav. Brain Res. 270, 261–269, (2014).
  • “Fragmentation Patterns of Aromatic 2,5-Diketopiperazines Using Liquid Chromatography/Mass Spectrometry”. Bratakos, S. M.; Sinanoglou, V. J.; Matsoukas, M. T.; Siapi, E.; Papahatjis, D. P.; Riganakos, K.; Zoumpoulakis, P. Curr. Anal. Chem. 12 (5), 439–449, (2016).
  • Liu Y.,; Lipin Ji,; Eno M.,; Kudalkar S.,; Ai-ling Li,; Schimpgen M.; Benchama O.; Morales P.; Xu S.; Hurst D.; iaoWu S.; Mohammad A.K.; Wood J.; Zvonok N.; Papahatjis D.; Zhou H.;  Honrao C.; Mackie K.; Reggio P.; Hohmann A.G.; Lawrence J. Marnett L.J.; Makriyannis A.; Nikas S.P. (R)-N-(1-Methyl-2-hydroxyethyl)-13-(S)-methyl-arachidonamide(AMG315): A novel chiral potent endocannabinoid ligand with stability to metabolizing enzymes. J. Med. Chem. 61, 8639-8657, (2018).
  • Theochari, I.; Papadimitriou, V.; Papahatjis, D.; Assimomytis, N.; Pappou, E.; Pratsinis, H.; Xenakis, A.; Pletsa, V. Oil-In-Water Microemulsions as Hosts for Benzothiophene-Based Cytotoxic Compounds: An Effective Combination. Biomimetics. 3, 13, (2018).
  • Goulielmaki, M.; Assimomytis, N.; Rozanc, J.; Taki, E.; Christodoulou, I.; Alexopoulos, G. L.; Zoumpourlis, V.; Pintzas A. and Papahatjis, D. DPS-2: A Novel Dual MEK/ERK and PI3K/AKT Pathway Inhibitor with Powerful Ex Vivo and In Vivo Anticancer Properties Translational Oncology. 12 (7), 932-950, (2019).
  • Theochari, I.; Ilic, T.; Nicolic, I.; Dobricic, V.; Tenchiou, A.; Papahatjis, D.; Savic, S.; Xenakis, A.; Papadimitriou, V.; Pletsa, V. Biological Evaluation of Oil-in-Water Microemulsions as Carriers of Benzothiophene Analogues for Dermal Applications. Biomimetics. 6, 10, (2021).

 

Patents

  • Patent application No 20050100282/08-06-2005/O.B.I.: ''Tissue specific antiestrogens selective for estrogen receptor alpha'' - Alexis MN, Papahatjis D, Assimomitis N, Siriani D, Sekeris CE.
  • GR 20180100094, WO2019171088A1 Applicant: NHRF, EP3761950A1, Applicant: Ioulia and Irene Tseti Pharmaceutical Laboratories SA. Inventors: Koufaki M., Calogeropoulou T., Chondrogianni N., Papahatjis D., Gonos E.S., Fotopoulou T., Proussis K., Chazapi E. “Bio-inspired proteasome activators with anti-ageing activity”

 

Meeting abstracts

  • Vasilopoulou M.A., Fotopoulou T., Papaevgeniou N., Gioran A., Papahatjis D., Calogeropoulou T., Koufaki M., Chondrogianni N. A novel bioinspired proteasome activator against aging Free Radic. Biol. Med. 2021, 177, S122- S123
  • Papaevgeniou N., Fotopoulou T., Vasilopoulou M., Panat N., Pick E., Golan A., Gonos E.S., Papahatjis D., Calogeropoulou T., Koufaki M., Chondrogianni N. A novel bioinspired proteasome activator: potential anti-ageing strategies offered by mother nature (but not only). Free Radic Biol Med. 2019, 139, S78-S79

 

 

 

© National Hellenic Research Foundation (NHRF), 48 Vassileos Constantinou Ave., 11635 Athens, Greece, Tel. +302107273700, Fax. +302107246618