INSTITUTE OF BIOLOGY, MEDICINAL CHEMISTRY & BIOTECHNOLOGY
 
  Drug Discovery
  Molecular Analysis
  Organic and Organometallic Chemistry
  Medicinal Chemistry
  Structural Biology & Chemistry
  Molecular Endocrinology
  Signal Mediated Gene Expression
  Molecular & Cellular Ageing
  Biomedical Applications
  Holistic Approaches in Health
  Chemical Carcinogenesis and Genetic Toxicology
  Metabolic Engineering-Bioinformatics
  Biotechnology
  Enzyme and Synthetic Biotechnology
  Biomimetics & Nanobiotechnology

Medicinal Chemistry

 

The Team focuses on the synthesis of new bioactive compounds for the prevention and treatment of diseases with high socioeconomic impact including neurodegenerative diseases and aging, cardiovascular diseases, analgesia and parasitic neglected diseases. A parallel research activity involves the development of synthetic methodology.

Research Team

Theodora Calogeropoulou, Ph.D.,  Researcher A'
Maria Koufaki, Ph.D.,  Researcher A'
Demetris Papahatjis, Ph.D., Researcher A'

Postdoctoral Researchers

Theano Fotopoulou, Ph.D.,
Nicolaos  Assimomytis, Ph.D.
Kyriakos Prousis, Ph.D., M.Sc.  Fellowship MEDEXIS

M.Sc. Students
Ms Ero Charalambous
Mr Ioannis Christopoulos

Young Research Collaborator
Ms P. Karakitsou

Diploma Students
Mr Vassilios Dimitriadis (Diploma thesis, TEI)
Ms Christina Kirkou (Diploma thesis, TEI)
Ms Efrosyni Nathanail (Diploma thesis, National Technical University of Athens)
Ms Evanthia Hazapi (Diploma thesis, Univ. of Crete)  

 

Current Projects

  • Synthesis of BRAFV600E  Inhibitors (purine, theophylline and benzothiophene analogues) for the development of agents against colorectal cancer.
  • Synthesis of Proteasome Activators (chroman or 5,7,8-trimethyl-1,4-benzoxazine/hydroxytyrosol hybrids) against aging. 
  • Chirospecific synthesis of novel endogenous and natural cannabinoid analogues.
  • Development of novel arachidonic acid cascade modulators.
  • Development of tissue-specific antiestrogens.
  • Design and synthesis of multifunctional antioxidants bearing five-membered heterocycles, such as oxadiazoles, 1,2,3-triazole, tetrazole and isoxazole. These heterocycles are potential pharmacophores and have been utilized as ester or amide bioisosteres in the search for compounds with superior pharmacokinetic profiles.
  • Design and synthesis of heterocyclic compounds with multifunctional pharmacological profile:
    • Possessing neuroprotective activity
    • Tyrosinase modulators
  • Design and synthesis of purine and adenosine analogues bearing nitrate esters, mimicking and/or enhancing endogenous cardioprotective mechanisms (ischemic preconditioning and postconditioning) in vivo.
  • Design and synthesis of novel neurosteroid analogues with neuroprotective activity mimicking Nerve Growth Factor activity.
  • Design and synthesis of antiprotozoal constrained ether phospholipids.    
  • Design and synthesis of fluorescent bioactive compounds and probes for mechanistic studies and imaging.
  • New synthetic technology enabling the synthesis of conformationally constrained bioactive molecules.
  • Organocatalysis: asymmetric Aldol and Michael reactions in aqueous media.
  • Development of synthetic methodology using microwave or ultrasound irradiation.


 

SELECTED RESEARCH HIGHLIGHTS

Chirospecific synthesis of novel endogenous and natural cannabinoid analogues.

  • Figure 4The tricyclic structures are very well recognized by both CB1 and CB2 receptors.
    Our results support the hypothesis for a subsite within CB1 and CB2 binding domain at the level of the benzylic side chain carbon in (-)-Δ8-THC series.

  • Differences in the size of C1’-ring substituents can be used to optimize selectivity for CB1.

  • End carbon substitution at the side chain is well tolerated

 

Development of novel arachidonic acid cascade modulators.

  • Development of enantioselective synthesis of novel methyl-substituted arachidonic acid derivatives.
  • (13S)-Methyl-substituted anandamide analogues were found to possess
    remarkably high affinity for the CB1 cannabinoid receptor.

 

Design and synthesis of multifunctional antioxidants bearing five-membered heteroaromatics.

  • New bioinspired synthetic antioxidants encompassing structural motifs of natural antioxidants and their bioisosteres (Vitamin E, Lipoic Acid, Caffeic Acid).
  • The majority of the new compounds displayed neuroprotective activity against oxidative stress induced cell death (oxytosis) using the hippocampal cell line HT22, with EC50values in the nanomolar range.
  • In vivo anti-aging activity in the C. elegans model.

 

Design and synthesis of heterocyclic compounds with multifunctional pharmacological profile

  • 1,4-Benzoxazines are considered privileged structures, isosteres of the chroman moiety.
  • 5,7,8-Trimethyl-1,4-benzoxazine analogues displayed neuroprotective activity against oxidative stress induced cell death in the nanomolar range.
  • The most active analogues protect the retina in the model of AMPA excitotoxicity.
  • All analogues were active against Toxoplasma gondii.

 

Design and synthesis of purine and adenosine analogues bearing nitrate esters, mimicking and/or enhancing endogenous cardioprotective mechanisms (ischemic preconditioning and post-conditioning) in vivo.

  • New class of compounds triggering endogenous cardioprotective mechanisms to limit infarct size after reperfusion of the ischemic myocardium.
  •  Novel pharmacological agents that could be used as mimics or enhancers of ischemic preconditioning or postconditioning, acting on intracellular pathways involved in these processes.

 

Design and synthesis of antiprotozoal constrained ether phospholipids

  • Introduction of rings in the lipid portion of ether phospholipids results in high activity and reduced host toxicity with respect to the current drug Miltex® (hexadecylphosphocholine).

  • More than 120 compounds were synthesized including click phospholipids and hybrids with antileishmanial dinitroanilines.

  • In vivo activity in mice infected with Leishmania infantum.

  • In  vivo  activity  of  an  oral  formulation  in  dogs  infected  with  kala-azar   (canine Leishmaniasis)

 

Design and synthesis of novel neurosteroid analogues with neuroprotective activity mimicking Nerve Growth Factor activity

  • 17-Spiroepoxy-DHEA derivatives up to micromolar range concentrations, are unable to activate estrogen receptors ERα,ERβ and androgen receptors or to interfere with ER- and AR-dependent gene expression.
  • They are unable to stimulate the growth of Ishikawa, MCF-7 and LNCaP cells.
  • They exhibit neuroprotective and immnunomodulatory properties and promote neurogenesis.

 

Current Collaborations


National
Prof. A. Gravanis, Medical School, University of Crete
Prof. C. Stournaras, Medical School, University of Crete
Prof. V. Roussis, Pharmacy Department, University of Athens
Prof. A. Tsotinis, Pharmacy Department, University of Athens
Prof. E. Iliodromitis, Medical School, University of Athens, Greece
Prof. K. Thermos, Medical School, University of Crete
Asc. Prof. P. Papazafiri, Department of Biology, University of Athens
Ass. Prof. I. Charalampopoulos, Medical School, University of Crete
Ass. Prof. E. Scoulica, Medical School, University of Crete
Ass. Prof. I. Andreadou, Pharmacy Department, University of Athens
Ass. Prof. G. Panagis, School of Social Sciences, University of Crete
Ass. Prof. K. Antoniou, Medical School, University of Ioannina
Ass. Prof. A. Detsi, Department of Chemical Engineeering, National Technical University of Athens

 

International

Prof. A. Makriyannis, Northeastern University, Center for Drug Discovery, Boston, USA
Dr S. Nikas, Northeastern University, Center for Drug Discovery, Boston, USA
Prof. G. Campiani, University of Sienna, Italy
Prof. M. Bradley, Chemistry Department, University of Edinburgh, UK
Prof. J.-L. Connat, University of Burgundy, Dijon, France
Prof. M.-P. Costi, Pharmacy Department, University of Modena and Reggio Emilia, Italy
Dr J. Clos, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany
Dr A. Cordeiro-da-Silva, Instituto de Biologia Molecular e Celular, Porto, Portugal
Prof. S. Otto, University of Groningen, Netherlands
Prof. S. Mangani, University of Siena, Italy
Prof. J.M. Alunda, Universidad Complutense de Madrid, Spain
Dr N. Martinet, Inst. Chimie Nice, France
Dr S. Golič Grdadolnik, Institute of Chemistry, Ljubljana, Slovenia
Dr M. Sokovic Inst. Biol. Res. “Sinisa Stankovic”  Belgrade, Serbia
Prof. A. Khalid, National Center for Research, Khartoum, Sudan
Dr M. Comini, Institut Pasteur de Montevideo, Uruguay
Prof. W. De Souza, Asc. Prof. R. Vommaro, Ass. Prof. J. Rodriguez, Federal University of Rio de Janeiro, Brazil
Dr L. Freitas Jr, Brazilian Biosciences National Laboratory (LNBio), Campinas, Brazil

 

SMEs and Spin-off Companies

MAKScientific, Boston, USA.
Heidelberg Institute for Theoretical Studies, Germany
Tydock Pharma, Modena, Italy
Hypha Discovery, UK
European Screening Port, Hamburg, Germany
COHIRO, Dijon,  France
BIONATURE EA, Herakleion, Greece

 

Research funding 2005-to date

EUROPEAN

  • FP7-HEALTH-2013-INNOVATION-1 (2014-2017) “New Medicines for Trypanosomatidic Infections”
  • FP7-2009-REGPOT-1 (2010-2013)  ¨Advancement of Research Capability for the Development of New Functional Compounds (ARCADE).
  • FP6. Marie Curie Transfer of Knowledge Programme - MTKD-CT-2004-014399 (2005-2009) "Solid-phase phospholipid and dendrimer synthesis" (SOPHOLIDES)
  • FP6. Marie Curie  Host fellowships for Early Stage Research Training (EST) (2006-2009). EURODESY: A European Research Training Site for the Design and Synthesis of Novel Neuroprotective and Hypoglycaemic Agents through a Multi-disciplinary approach.

 

NATIONAL

  • Research Funding Program KRIPIS: Project STHENOS: "Targeted therapeutic approaches against ageing and degenerative diseases, cancer in particular", (2013-2015).
  • Kouponia Kainotomias for SMEs (2011-2012).
  • Hellenic Society Of Cardiology(2007-10)Synthesis of nicorandil and adenosine derivatives as triggers of pharmacological preconditioning” (2010-12)Development of agents mimicking postconditioning” .
  • Excellence in the Research Institutes supervised by the Greek General Secretariat for Research and Technology EPAN 3.3.1. (2006-2009). “Design and synthesis of bioactive and functional materials”.
  • E2050-4/2 Greek Ministry of Development (2006-09)  “Design and Synthesis of Bioactive Molecules”.
  • Operational Programme for Competitiveness, GSRT YB/60 (2004-07). “Exploitation of novel cannabinoid analogs with possible analgesic, psychomotor and anti-abuse potential”.
  • Operational Programme for Competitiveness, GSRT YB/39 (2004-07) “Therapeutic Interventions Against Protozoan Infections”
  • Bilateral Collaboration of Greece–Hungary (2003-06) “Synthesis of novel antiarrhythmics and study of their electrophysiological effects” .
  • PENED 2001 GSRT (2002-2006). “Investigation of the mechanisms of action of neuroprotective neurosteroids. Development of new compounds with high neuroprotective and low estrogenic or androgenic activity” .
  • GSRT programme “Location and use of research results by the creation of new enterprises” (Spin-off, 2003-05) “Cannabinomimetic Analogs with Therapeutic Applications”
  • GSRT programme “Location and use of research results by the creation of new enterprises” (Spin-off, 2003-05)  “New ether phospholipids as ultrasound contrast agents”.
  • Bilateral Collaboration of Greece–Hungary (2002–2005) “Neuroactive steroids and ionotropic neurotransmitter receptors” . 
  • Excellence in the Research Institutes supervised by the Greek General Secretariat for Research and Technology EPAN 3.3.1.  (2002-2005). “Novel strategies against neurodegeneration”.

 

Contract Research

  • Professional Services Agreements with UNI-PHARMA. S.A. (2011-2012).
  • Research collaboration with Medexis SA (2008-2010) “Synthesis and Study of Na+, K+-ATPase inhibitors”
  • Professional Services Agreements with Northeastern University, Center for Drug Discovery (2008-2010). "Multistep synthesis of bicyclic and tricyclic cannabinoids and Synthesis of inhibitors of FAAH and/or MGL.
  • Research collaboration with Medexis SA (2006-2008) “Synthesis and Study of steroid-protein conjugates.
  • Professional Services Agreement with Northeastern Univiveristy, Center for Drug Discovery (2006-07) “Synthesis of tropolone derivatives”.
  • Research collaboration with Medexis SA (2005-2006) “Total synthesis of ribenol and derivatives thereof”.
  • University of Connecticut Professional Services Agreement No 4505 (2004-05) "Novel Antioxidants and Bioactive ether phospholipids"


PUBLICATIONS IN PEER REVIEWED JOURNALS

2014

Koufaki M.*, Fotopoulou T., Heropoulos G.A. Synergistic effect of dual-frequency ultrasound irradiation in the one-pot synthesis of 3,5-disubstituted isoxazoles. Ultrason. Sonochem. 2014, 21, 35-39.

2013 

Polissidis A., Galanopoulos A., Naxakis G., Papahatjis D., Papadopoulou-Daifoti Z., Antoniou K. The cannabinoid CB1 receptor biphasically modulates motor activity and regulates dopamine and glutamate region dependently. Int. J. Neuropsychopharmacol. 2013, 16, 393-403.

Godinho  J., Georgikopoulou K., Calogeropoulou T., de Souza W., Rodrigues J.  A novel phosphocholine dinitroaniline hybrid molecule exhibits biological activity in vitro against Leishmania amazonensis.  Exp. Parasitol. 2013, 135, 153–165.

Vila T. V. M., Ishida K., de Souza W.,  Prousis K. C., Calogeropoulou T., Rozental S. Effect of alkylphospholipids on Candida albicans biofilm formation and maturation J. Antimicrob. Chemother. 2013, 68, 113-125.

Prousis K. C., Tzani A., Avlonitis N., Calogeropoulou T., Detsi A.  Reactivity of  2-methyl-4H-3,1-benzoxazin-4-ones and  2-methyl-4H-pyrido[2,3-d][1,3]oxazin-4-one under Microwave Irradiation  Conditions. J.  Het.  Chem. 2013, 50, 1313-1321.

Dimas K., Papadopoulou N., Baskakis C., Prousis K. C., Tsakos M., Alkahtani S., Honisch S., Lang F., Calogeropoulou T., Alevizopoulos K., Stournaras C. Steroidal Cardiac Na+/K+ ATPase Inhibitors Exhibit Strong Anti-Cancer Potential in Vitro and in Prostate and Lung Cancer Xenografts in Vivo. Anticancer Agents Med. Chem. 2013, BSP-CMCACA-2013-187 (http://www.ncbi.nlm.nih.gov/pubmed/24066843)

Prousis K. C., Avlonitis N., Heropoulos G. A.; Calogeropoulou T.* FeCl3-catalysed ultrasonic-assisted, solvent-free synthesis of 4-substituted coumarins. A useful complement to the Pechmann reaction. Ultrason. Sonochem. 2013  http://dx.doi.org/10.1016/j.ultsonch.2013.10.018.

2012

Koufaki M.*, Fotopoulou T., Iliodromitis E. K., Bibli S. I., Zoga A., Kremastinos D. Th., Andeadou I.  Discovery of 6-[4-(6-nitroxyhexanoyl)piperazin-1-yl)]-9H-purine, as pharmaco- logical post-conditioning agent. Bioorg. Med. Chem. 2012, 20, 5948-5956.

Koukouli F., Paspaltsis I., Salta E., Xanthopoulos K., Koini E. N., Calogeropoulou T., Sklaviadis, T. Inhibition of PrPSc formation in scrapie infected N2a cells by 5,7,8-trimethyl-3,4-dihydro-2H-1,4-benzoxazine derivatives. Prion  2012, 6, 470-476.

Gravanis A., Calogeropoulou T., Panoutsakopoulou V., Thermos K., Neophytou C., Charalampopoulos, I. Microneurotrophins: Neurosteroids bind to NGF receptors, inducing pro- survival signalling in neuronal cells. Science Signal. 2012, 5 (246), art. no. pt8.

Koini  E.N., Avlonitis N., Martins-Duarte E.S., de Souza W., Vommaro R.C., Calogeropoulou T.* Divergent synthesis of 2,6-diaryl-substituted 5,7,8-trimethyl-1,4-benzoxazines via microwave-promoted palladium-catalysed Suzuki-Miyaura cross coupling and biological evaluation. Tetrahedron 2012, 68, 10302-10309.

2011

Koini E.N., Avlonitis N., Calogeropoulou T.* Simple and Efficient Method for the Halogenation of Oxygenated Aromatic Compounds. SYNLETT 2011, 1537.

Filippou P.S., Koini E. N.,  Calogeropoulou T.,  Kalliakmani P., Panagiotidis C.A., Kyriakidis D. A. Regulation of the Escherichia coli AtoSC two component system by synthetic biologically active 5;7;8-trimethyl-1;4-benzoxazine analogues. Bioorg. Med. Chem. 2011, 19, 5061-5070.

Lazaridis I., Charalampopoulos I., Alexaki V.-I., Avlonitis N., Pediaditakis I., Efstathopoulos P., Calogeropoulou T., Castanas E., Gravanis A. Neurosteroid Dehydroepiandrosterone Interacts with Nerve Growth Factor (NGF) Receptors, Preventing Neuronal Apoptosis. PloS Biol. 2011, 9 (4): e1001051.

Koufaki M.*, Tsatsaroni A., Alexi X., Guerrand H., Zerva S., Alexis M. N. Isoxazole substituted chromans against oxidative stress-induced neuronal damage. Bioorg. Med. Chem. 2011, 19, 4841-4850.

2010

Papahatjis D. P.*, Nahmias V., Nikas S.P., Schimpgen M., Makriyannis A. Design and Synthesis of (13S)-Methyl Substituted Arachidonic Acid Analogs: Templates for Novel Endocannabinoids  Chem.-Eur. J. 2010,
16
, 4091-4099.

Koufaki M.*, Theodorou E., Alexi X., Nikoloudaki F., Alexis M.N. Synthesis of tropolone derivatives and evaluation of their in vitro neuroprotective activity. Eur. J. Med. Chem.2010, 45, 1107-1112.

Koufaki M.*, Theodorou E., Alexi X., Alexis M.N. Synthesis of a second generation chroman/catechol hybrids and evaluation of their activity in protecting neuronal cells from oxidative stress-induced cell death. Bioorg. Med. Chem. 2010, 18, 3898-3909

Nikas S.P., Alapafuja S.O., Papanastasiou I, Paronis C.A., Shukla V.G., Papahatjis D.P., Bowman A.L., Halikhedkar A., Han X., and Makriyannis A. Novel 1′-1′ Chain Substituted Hexahydrocannabinols:9β-Hydroxy-3-(1-hexyl-cyclobut-1-yl)-hexahydrocannabinol (AM2389) a Highly Potent Cannabinoid Receptor 1 (CB1) Agonist.  J. Med. Chem., 2010  53,  6996-7010.

Papanastasiou I.,  Prousis  K.C, Georgikopoulou K., Pavlidis T.,  Scoulica E., Kolocouris N., Calogeropoulou T.* Design and synthesis of new adamantyl-substituted antileishmanial ether phospholipids  Bioorg. Med. Chem. Lett.  2010  20 (18), 5484-5487.

2009

Koufaki M.*, Detsi A., Kiziridi C. Multifunctional lipoic acid conjugates. Curr. Med. Chem. 2009, 16, 4728-4742.

Koini E.N., Papazafiri P., Vassilopoulos A., Koufaki M., Horváth  Z.,  Koncz I., Virág L., Papp G.J., Varró A., Calogeropoulou  T.* 5,7,8-Trimethyl-benzopyran and 5,7,8-Trimethyl-1,4-benzoxazine aminoamide derivatives as novel antiarrhythmics against ischemia-reperfusion injury. J. Med. Chem. 2009, 52, 2328-2340.

Melagraki G., Afantitis A., Igglessi-Markopoulou O., Detsi A., Koufaki M., Kontogiorgis C., Hadjipavlou-Litina D. J. Synthesis and evaluation of the antioxidant and anti-inflammatory activity of novel coumarin-3-aminoamides and their alpha-lipoic acid adducts. Eur. J. Med. Chem. 2009, 44, 3020-3026. 

Koufaki M.*, Kiziridi C., Alexi X., Alexis M. N. Design and synthesis of novel neuroprotective 1,2-dithiolane/chroman hybrids. Bioorg. Med. Chem. 2009, 17, 6432-6441.

2008

Calogeropoulou T.,*  Angelou P., Detsi A., Fragiadaki I., Scoulica E. Design and synthesis of potent antileishmanial cycloalkylidene-substituted ether phospholipid derivatives. J. Med. Chem. 2008, 51, 897-908.

Fotopoulou T., Iliodromitis E. K., Koufaki M.*, Tsotinis A., Zoga A., Gizas V., Pyriochou A., Papapetropoulos A., Andreadou I., Kremastinos D. Th. Design and synthesis of nitrate esters of aromatic heterocyclic compounds as pharmacological preconditioning agents. Bioorg. Med. Chem. 2008, 16, 4523-4531.

Andreadou I., Koufaki M., Iliodromitis E. K., Kremastinos D. Th. Pharmacological pre- and post- conditioning agents: reperfusion-injury of the heart revisited. Mini Rev. Med.Chem. 2008, 8, 952-959.

Andreadou I., Iliodromitis  E. K., Farmakis D., Koufaki M., Tsotinis A., Kremastinos D. Th. Alternative pharmacological interventions that limit myocardial infarction. Curr. Med. Chem. 200815, 3204-3213. 

Wiesbrock F., Patteux C., Olszewski T. K.,  Blanrue A., Heropoulos G. A., Steele B. R., Micha-Screttas M., Calogeropoulou, T.* Solution-Phase Synthesis and Scale-Up of 1st Generation Tetraester-Dendritic Branches  Involving Microwave Irradiation and/or Ultrasound. Eur. J. Org. Chem. 2008, 4344-4349.

2007

Papahatjis D. P.*, Nahmias V., Nikas S. P., Andreou T., Alapafuja S. O., Tsotinis A., Guo J., Fan P., Makriyannis A. The C1´-Cycloalkyl Side Chain Pharmacophore in Tetrahydrocannabinols. J. Med. Chem.
2007
, 50, 4048-4060.

Tsotinis T., Vlachou M., Papahatjis D. P., Nikas S. P., Sugden D. An Efficient Synthesis of Simple β,β'-Cyclobisalkylated Melatoninergic Phenylalkylamides. Lett. Org. Chem. 2007, 4, 92-95.

Durdagi S., Kapou A., Kourouli T., Andreou T.,  Nikas S.P., Nahmias V., Papahatjis D. P., Papadopoulos M. G., Mavromoustakos T. 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.
J. Med. Chem. 2007, 50, 2875-2885.

Khanolkar A. D., Dai Lu T., Malan P. Jr., Ibrahim M., Porreca F., Thakur G.A., Veerappan V., Duclos R. I. Jr., Tian X., George C., Parrish D. A., Papahatjis D. P., Makriyannis A. Cannabilactones: A Novel Class of CB2 Selective Agonists with Peripheral Analgesic Activity. J. Med. Chem. 2007, 50, 6493-6500.

Durdagi  S., Papadopoulos  M. G., Papahatjis  D. P., Mavromoustakos  T. Combined 3D QSAR and molecular docking studies to reveal novel cannabinoid ligands with optimum binding activity. Bioorg. Med. Chem. Lett. 2007, 17, 6754-6763.

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 M. P., Thermos K., Daifoti-Papadopoulou Z., Papahatjis D. P., Spyraki C. Novel ligands for cannabinoid receptors: Pharmacological studies. Behav. Pharmacol. 2007, 18, 24, supp. 1.

Durdagi S., Koukoulitsa C., Kapou A., Kourouli T., Andreou T., Nikas S. P., Nahmias V.,  Papahatjis D. P., Papadopoulos M. G., Mavromoustakos T. Testing the 3D QSAR/ComFA-CoMSIA results of flexible bioactive compounds with molecular docking studies. Drugs Future 2007, 32, supp A, 79.

Detsi A, Bouloumbasi D., Prousis K. C., Koufaki M., Athanasellis G., Melagraki G., Afantitis A., Igglessi-Markopoulou O., Kontogiorgis C., Hadjipavlou-Litina D. J. Design and synthesis of novel quinolinone-3-aminoamides and their α-lipoic acid adducts as antioxidant and anti-inflammatory agents. J. Med. Chem. 2007, 50, 2450-2458.

Koufaki M.*, Kiziridi C., Nikoloudaki F., Alexis M.N. Design and synthesis of 1,2-dithiolane derivatives and evaluation of their neuroprotective activity. Bioorg. Med. Chem. Lett. 2007, 17, 4223-4227.

Kapou A., Benetis, N. P., Avlonitis N., Calogeropoulou T., Koufaki M.. Scoulica E., Nikolaropoulos S.S.,  Mavromoustakos T. 3D-Quantitative Structure-Activity Relationships of New Synthetic Antileishmanial Ring-Substituted Ether Phospholipids. Bioorg. Med. Chem. 2007, 15, 1252-1265.

Xilouri M., Avlonitis N., Calogeropoulou T., Papazafiri  P.  Neuroprotective effects of steroid analogues on P19-N neurons. Neurochem. Int. 2007, 50, 660-670.

Karanikolopoulos N., Pitsikalis M. , Hadjichristidis N. , Georgikopoulou K.,  Calogeropoulou, T., Dunlap J. R. pH-Responsive Aggregates from Double Hydrophilic Block Copolymers Carrying Zwitterionic Groups. Encapsulation of Antiparasitic Compounds for the Treatment of Leishmaniasis. Langmuir 2007, 23, 4214-4224.

Maksay G., Fodor L., Bíró T., Avlonitis N., Calogeropoulou T.  A 17b-derivative of allopregnanolone is a neurosteroid antagonist of a cerebellar subpopulation of GABAA receptors with nanomolar affinity.  Brit. J. Pharmacol. 2007, 151, 1078-1086. 

2006

Koufaki M.*, Theodorou E., Galaris D., Nousis L., Katsanou E. S, Alexis M. N. Chroman/catechol hybrids: Synthesis and evaluation of their activity against oxidative stress induced cellular damage. J. Med. Chem. 2006, 49, 300-306.

Koufaki M.*, Kiziridi C., Papazafiri P., Vassilopoulos A., Varró A., Nagy Z., Farkas A., Makriyannis A. Synthesis and biological evaluation of benzopyran analogues bearing class III antiarrhythmic pharmacophores. Bioorg. Med. Chem. 2006, 14, 6666-6678.

Papahatjis D. P.*, Kourouli T., Nahmias V. A Convenient Preparation of Enantiomerically Pure Esters of trans-Epoxysuccinic Acid. Lett. Org. Chem. 2006, 3, 45-47.

Papahatjis D. P.*, Nahmias V., Andreou T., Fan P., Makriyannis A. Structural Modifications of the Cannabinoid Side Chain towards C3-Aryl and 1΄,1΄-Cycloalkyl-1΄-Cyano Cannabinoids. Bioorg. Med. Chem.  2006, 16, 1616-1620.

Tsotinis A., Vlachou M., Papahatjis D.P., Calogeropoulou T., Nikas S. P., Garratt P.J., Piccio V., Vonhoff S., Davidson K., The M. T., Sugden D. Mapping the melatonin receptor. 7. Subtype selective ligands based on beta-substituted N-acyl-5-methoxytryptamines and beta-substituted N-acyl-5-methoxy-1-methyltryptamines. J. Med. Chem. 2006, 49, 3509-3519.

Thermos K., Papazoglou M., Antoniou K., Mastrodimou N., Panagis G., Vlachou S., Renieri E., Nahmias V., Menissiou A., Gianni M., Kondylis M. P., Daifoti-Papadopoulou Z., Papahatjis D. P., Spyraki C. Pharmacological characterization of novel ligands for CB1 and CB2 cannabinoid receptors. Acta Pharmacol. Sin. 2006, 27, 394-395 Suppl. 1.

Charalampopoulos I.,  Alexaki V.-I., Lazaridis I.,  Dermitzaki E.,  Avlonitis N., Tsatsanis C., Calogeropoulou T.,  Margioris A. N.,  Castanas E.,  Gravanis A. G protein-associated, specific membrane binding sites mediate the neuroprotective effect of Dehydroepiandrosterone.  FASEB J. 2006, 20, 577-579.

2005

Souli C.,  Avlonitis N., Calogeropoulou T.*, Tsotinis A., Maksay G., Bíró T., Politi A., Mavromoustakos T., Makriyannis A., Reis H., Papadopoulos M. Novel 17β-substituted conformationally constrained neurosteroids that modulate GABAA receptors. J. Med. Chem. 2005, 48, 5203-5214.

Papazafiri P., Avlonitis N., Angelou P., Calogeropoulou T.*, Koufaki M., Scoulica E., Fragiadaki I. Structure-activity relationships of antineoplastic ring-substituted ether phospholipid derivatives. CancerChemother. Pharmacol. 2005, 56, 261-270.

Detsi A.,  Roussis V., Tsotinis A.,  Roussakis C.,  Calogeropoulou T.* A Concise Approach to Benzoic Acid Derivatives Bearing an a,b-Unsaturated Ketone Substituent: Synthesis of Methyl Taboganate.
SYNLETT
 2005, 3131-3135.

Antoniou K., Galanopoulos A., Vlachou S., Nahmias V., Thermos K., Panagis G., Daifoti Z., Marselos M., Papahatjis D. P., Spyraki C. Preclinical behavioral evaluation of a novel cannabinoid analogue. Rev. Clinical Pharmacol. Pharmacokinet. 2005, 23, 26-28.

Antoniou K., Galanopoulos A., Vlachou S., Kourouli T., Nahmias V., Thermos K., Panagis G., Daifoti Z., Marselos M., Papahatjis D, Spyraki C. Behavioral pharmacological properties of a novel cannabinoid 1’,1’-dithiolane  Δ8-THC analogue,  AMG-3. Behav.Pharmacol. 2005, 16, 499-510.

 

PATENTS

1.  US 8,097,752   (issued 17-1-2012) "Antiprotozoal ring-substituted phospholipids"
Inventors: T. Calogeropoulou, M. Koufaki, N. Avlonitis, A. Makriyannis.
2.  GR20050100100 (2/3/05) “Ultrasound contrast agents containing anticancer ether phospholipids”  
Inventors: T. Calogeropoulou, M. Koufaki.
3.  GR 1003725 "Bifunctional agents possessing antioxidant and antiarrhythmic activity"
Applicants and Inventors: M. Koufaki, T. Calogeropoulou, A. Makriyannis.
4. WO 0204438, US2004259763, CA2415523, EP1301504 , DE60106922T "Bifunctional agents possessing antioxidant and antiarrhythmic activity"
Applicant: UNI-PHARMA S.A.  Inventors: M. Koufaki, T. Calogeropoulou, A. Makriyannis.
5. GR 1003861  “GABAA MODULATING NEUROSTEROIDS”
Inventors: T.  Calogeropoulou, C. Souli, A. Tsotinis, A. Makriyannis
6.  US2005176976, US7064116, WO02053577,  GR-1003861, AU2002217353 “GABAA MODULATING NEUROSTEROIDS »
Inventors: T.  Calogeropoulou, C.  Souli, A. Tsotinis, A. Makriyannis.
7. GR 20050100282: ''Tissue specific antiestrogens selective for estrogen receptor alpha''
Inventors: Alexis MN, Papahatjis D, Assimomytis N, Siriani D, Sekeris CE.
8. GR20080100530 “1,4-Benzoxazine Derivatives”
Inventors: Calogeropoulou, T.,  Koini, E., Alexis, M.N., Avlonitis, N., Alexi, X.
9. WO2008155534, GB20070011948, CA2691071, AU2008265046, US2010234335, KR20100040292,  EP2158209, CN101784558, EA201070027    “Neurosteroid compounds”
Inventors:  Gravanis A., Calogeropoulou T., Charalampopoulos I., Avlonitis N., Castanas E., Margioris A., Tsatsanis C., Minas V., Alexaki  V.-I., Alexis M., Remboutsika E., Vergou B., Neophytou C.  Applicant: Bionature EA Ltd,Cyprus
10. US20100369568  “Compounds and methods for treating neoplasia”
Inventors: Alevizopoulos K.; Calogeropoulou T.; Stournaras C.
11.  WO2011030116, SG179049, CA2773600 “Use of steroid compounds for inflammatory and autoimmune disorders”
Inventors: Panoutsakopoulou V.; Angelakopoulou M.; Calogeropoulou T.; Gravanis A.; Lazaridis I.; Neophytou C.
Applicant: Bionature EA Ltd, Nicosia, Cyprus

 

Chapters in books

1. Maria Koufaki and Anastasia Detsi. Design and Synthesis of Antioxidant α-Lipoic Acid Hybrids. Advanced Protocols for Oxidative Stress II Series: Methods in Molecular Biology, Vol. 594, Armstrong, Donald (Ed.)
2010
, p. 297-309.
2. 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, “Putative Bioactive Conformers of Small Molecules: A Concerted Approach using NMR Spectroscopy and Computational Chemistry” In: Medicinal Chemistry Research Progress, G.P. Colombo and S. Ricci (Eds.), 2008, Nova Science Publishers, Inc.

 
 

 

 

 

 
 

 

   
       

 

 

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