Drug Discovery
  Molecular Analysis
  Organic and Organometallic Chemistry
  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
  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
  Enzyme and Synthetic Biotechnology
  Biomimetics & Nanobiotechnology
  Conjugated Polymers for Healthcare, Bioelectronics and Bioimaging


Dendrimer and Medicinal Chemistry
Dr Cecile Arbez-Gindre | Research Scientist, Group Leader



Main research directions/Ongoing research activities

Research in chemical biology, resulting from the increasing interaction between organic chemistry and biology, has gradually led to the identification of biological targets and the design of synthetic molecules with biological activities. Both nanomedicine and medicinal chemistry have focused on the discovery of drugs ideally suited to the prevention or treatment of human diseases such as cancer, inflammation or neurodegenerative diseases. Thus, it is strategically interesting for the design and the synthesis of well-defined custom materials with biomedical applications to capitalize on the expertise of dendrimer chemistry for the engineering of tunable biocompatible dendritic nanomolecules for nanomedicine or of medicinal chemistry for the synthesis of small compounds as potential drugs for specific biological targets.

By developing synthetic methodologies served by high energy technique (e.g microwave, ultrasound), we can access to biologically active small molecules or biocompatible nanostructures.


Research Activities Overview

Engineering of tunable biocompatible dendritic nanomolecules for nanomedicine

From classical dendrimer to amphiphilic dendrimer


Classical dendrimers are globular unimolecular species containing a core, multiple branching points and a single type of end group constituting their peripheral functionality. They are highly branched and well-defined polymers with precise characteristics resembling small vesicles. Their development in the fields of nanotechnology and materials sciences is considered a milestone in the engineering of macromolecules with a nanometric size (1-10 nm) allowing for passive targeting effects, that reduce the nonspecific toxicity of the drugs carried. Consequently, dendrimers have found a place as nanocarriers in the biomedical development of drug, gene or imaging delivery systems, as well as in tissue targeting, tumor therapy and diagnostics. Some of them are drugs per se.


Nevertheless, classical dendrimers are presenting several limitations; complex synthesis, organism’s rapid systemic clearance, significant toxicological issues depending on dendrimer generation, charges, and fragment accumulation, poor drug loading or difficulty to achieve a controlled drug release.

Therefore, the last decade, attention has been paid to smallest biocompatible dendritic structures (e.g dendrons, amphiphilic dendrimers) that present the advantage of moieties multivalence targeted presentation, and are more easily manageable and synthetically accessible.


Dendrons because they are molecules containing a functionalized branch with targeted end groups, and a focal point for possible conjugation with bioactive moieties, resulting in the formation of branched hybrid macromolecules whose biological activity is potentially enhanced by targeted multivalent presentation favoring supramolecular dynamics of interaction with complex biological systems.

Amphiphilic dendrimers because they are branched bi-functionalized molecules possessing self-assembly properties that allow the formation of largest non-covalent supramolecular structures mimicking globular covalent dendrimers, or because they can become components of other artificial complex highest nanosystems (e.g., liposomes, cubosomes, polymersomes, nanoemulsions, microemulsion) that with a plethora of applications in the neutra/pharmaceutical industry.


From classical to biocompatible glycodendrimers

imageCarbohydrates play a vital role through their interactions with lectins, which are specific carbohydrate binding proteins prevalent in living organisms implicated in intercellular recognition events such as cell adhesion and migration, cell differentiation and apoptosis, and infection by viral, parasitic and bacterial pathogens.

Lectins are usually aggregated into oligomeric structures which can also dissociate into dimers or monomers on whose surface a binding pocket is located. This provides a suitable arrangement for high affinity multivalent binding to suitable carbohydrate analogs.

image Current interest in the development of potential pharmaceuticals based on carbohydrate-lectin interactions has led to the synthesis of glycoconjugate compounds such as glycodendrimers with a multivalent carbohydrate periphery that confers a capacity of binding to biological macromolecules such as lectins via multiple and simultaneous non-covalent H-bonding interactions. These cooperative interactions confer high binding affinity and specificity to the carbohydrate-ligand complexes typically required to mediate the essential biological processes mentioned above and such compounds are foreseen to have a wide range of potential applications such as anti-adhesion drugs, drug delivery systems, functional antigens or anti-tumor vaccines.

Synthesis and pharmaceutical applications of glycerol- or glycodendrons containing an amino focal group for conjugation to biological active compounds


Previously, we reported the synthesis of low generation glycodendrimeric compounds (e.g. D2) and a crystallographic structural investigation of their cross-linking interactions (Fig2) with human galectin-7 (hGAl-7), a lectin involved in tumor growth [1].


Thermodynamic studies (Fig3) of the binding ability of our ligands to peanut agglutinin (PNA), a galactose recognizing lectin representing a suitable antibody mimic, also demonstrated that multivalent interactions induced a stronger stabilizing effect than the corresponding monosaccharide [2].

[1] Ramaswamy S., Sleiman M.H., Masuyer G., Arbez-Gindre C., Micha-Screttas M., Calogeropoulou T., Steele B.R. and Acharya K. R., “Structural basis of multivalent galactose-based dendrimer recognition by human galectin-7”, FEBS Journal, 2015, 282, 372–387,
[2] Fessas D., Micha-Screttas M., “Binding and stabilisation effects of glycodendritic compounds with peanut agglutinin”, Int. J. of Biological Macromolecules, 2015, 80, 692–701



In our laboratory, to design and synthesize biocompatible nanoscale dendritic macromolecules, we are using a combination of convergent and divergent methods of dendrimer synthesis based on microwave-assisted Huisgen key alkyne azide cycloaddition. This modular strategy is based on the versatile geometry of TRIS (monomer AB3) for a rapid dendritic growth of terminal branches containing glycerol- or disaccharide groups and the synthesis of cores of variable shape and symmetry to allow:


A globular dendrimer growth towards classical low generation dendrimers



A linear growth towards dendrons, bowtie or amphiphilic dendrimers




The conjugation of dendrons with biologically active compounds to produce hybrid compounds


imageBased on promising physicochemical and crystallographic results obtained from in vitro studies with lectin [1,2], various glycerol- and glycodendrons, containing the schematically described focal amino group, are used as versatile precursors for the construction of small libraries of molecules used in various areas of interest as:


1. Tools for the studies of carbohydrate-lectin interactions image


2. Nanostructures for proteasome activation image


3. Biotin-modified dendron for non covalente conjugation with high-affinity folate nanosystems image


4. Components for chimeric liposomal systems with glycodendronized surfaces enhancing liposomal biocompatibility and lectin targeting properties image


5. Biocompatible delivery system with fluorescent properties for encapsulation of hydrophobic natural substances image


6. Probes for the study of artificial membranes: tailored in-house spin probe tools for structural exploration of colloidal systems


These different projects are part of previous or undergoing collaborations
1) Prof. D. Fessas, DiSTAM, Univ. of Milano, Italy and Prof. K. Ravi Acharya, Department of Biology and Biochemistry, University of Bath (UK) 2) Dr. N. Chrondogianni/ Laboratory of Molecular & Cellular Ageing/ ICB/NHRF 3) Dr. D. Appelhans, Leibniz Institute of Polymer Research, Dresden, Germany 4) Prof. K. Demetzos, Dr. M. Chountelisi, Dr. N. Nazarisis, Laboratory of Pharmaceutical Nanotechnology/ Department of Pharmacy of the School of Health Sciences/ National and Kapodistrian University of Athens 5) Dr. S. Pispas and Dr. A. Papagianopoulos, Laboratory of Materials Synthesis and Physical Chemistry, Theoretical & Physical Chemistry Institute/NHRF 6) Dr. A. Xenakis, Dr. V. Papadimitriou, Dr. M. Zoumpanioti, Laboratory of Biomimetics & Nanobiotechnology ICB/NHRF.

Synthesis of small compounds as potential drugs for specific biological targets

Proteasome activators


The effect on proteasome activity and function of nanosized amphiphilic molecules synthesized by hybridization of an anti-oxidant moiety with an amino block grafted with carbohydrate or glycerol groups, was studied after improvement of the synthetic route leading to these analogues. Based on biological assays, one of the dendritic compound appears to be involved in the activation of the proteasome indicating that the use of such hybrid molecules may be interesting in anti-aging strategy.

This project is part of a close collaboration within the ICB/NHRF with Dr. N. Chrondogianni, Laboratory of Molecular & Cellular Ageing for testing of hybrid dendritic molecules as proteasome activator with anti-ageing properties


Selective non-steroidal glucocorticoid receptor (GR) agonists


There is a need to develop new drugs with the therapeutic advantages of classical glucorticosteroids, but with a reduced side-effect profile. The recent discovered of 1,3-benzothiazole analogues as a new class of genuine SEGRA (Selective Glucocorticoid Receptor Agonists, SEGRA) paves the way for hit-to-lead optimization. Therefore, in accordance with preliminary in silico studies and with the aim to develop novel potent anti-inflammatory drugs, a series of modified imino-benzothiazole-thioacetamides has been designed, synthesized, and subjected to biological evaluation. Between the 3 derivatives found to inhibit hydrocortisone-mediated transactivation, presumably through GR binding and hydrocortisone displacement, one of them gave very interesting results but simultaneously exhibited toxicity and solubility problems. Thus, structural modifications are necessary to confirm the value of further research in this direction.

This project is part of a close collaboration inside the ICB/NHRF with Dr. M. Zervou, Laboratory of Molecular Analysis for the rational design of SEGRA derivativesandwith Dr. D. Mitsiou, Laboratory of Molecular Endocrinology for testing some synthesized imino-amino benzothiazole derivatives.


Education & Training

Training, guiding of undergraduate, graduate, master students, and post-doctoral fellows.



Group Structure and Personnel

Cécile Arbez-Gindre, Group leader, Senior Research Scientist
Maria Micha-Screttas, Researcher Emeritus
George Heropoulos, Researcher Emeritus
Georgia Antonopoulou, Scientific Technical personnel

Postdoctoral Researchers
Theano Fotopoulou (2018)
Alia Tenchiu (2018)
MSc students
Katerina Nasaj (2018)
Petros Siapkaras (2019)



Our activities have been supported and inspired by inherent, fruitful collaborations 1) within our institute 2) within our foundation (with the Laboratory of material synthesis and physical chemistry of the Theoretical and Physical Chemistry Institute) 3) with the Laboratory of Pharmaceutical Technology and Nano-Technology, of the Department of Pharmacy of the National and Kapodistrian University of Athens 4 ) but also from abroad with our member ship to the committee management of  COST Action CA17140  Cancer nanomedicine: from the bench to bedside; (2018-2023)  coordinated by Prof. Barbara Klajnert-Maculewicz (Łodz, Poland) and lately by Prof. Sabrina Pricl (Trieste, Italy) that is bringing together 40 countries and involves business, clinical, and institutions. previously.



Our activities have been supported by the matching funds of REGPOT-2009-1 (FP7)- ARCADE- Advancement of Research Capability for the Development of New Functional Compounds and the Developmental Projects of Research Organizations- KRIPIS. National Strategic Reference Framework, Action 1) STHENOS (2013-2015) Targeted therapeutic approaches against degenerative diseases, with special focus on cancer&ageing 2) STHENOS-B (2017-2021) with special focus on Optimization of the targeted bioactive molecules and the matching funds of “ARCADE”.



PhD thesis

Arbez-Gindre Cécile (1997): “Synthesis of double [13-C] labelled cutaneous metabolites of allergenic corticosteroids. Interaction studies with proteins”, PhD in Organic Synthesis/Medicals Sciences, Université Louis Pasteur, Strasbourg I, France


Chapter of Book/Review Article

Chountoulesi M., Naziris N., Gioran A., Papagiannopoulos A., Steele B. R., Micha-Screttas M., Stravrinides S. G., Hanias M., Chondrogianni N., Pispas S., Arbez-Gindre C., Demetzos C., (2022) “Applications of Nanotechnology in Alzheimer’s Disease." In: Vlamos P., Kotsireas I.S., Tarnanas I. (eds)
Handbook of Computational Neurodegeneration. Springer Nature Switzerland AG, Cham. (In press)


Peer-reviewed journals

  • Ioannou P.-C., Arbez-Gindre C., Zoumpanioti M., Raptopoulou C.P., Psycharis V., Kostas I.D., Kyritsis P., “Catalytic reactivity of the complexes [Pd{(Ph2P)2N(tBu)-P,P´}X2], X = Cl, Br, I, in the Suzuki-Miyaura C−C coupling reaction: Probing effects of the halogeno ligand X– and the ligand’s tBu group”. J. Organomet. Chem., 2019, 879, 40–46; IF=2.22 (2020-2021)
  • Khemakhem M., Papadimitriou V., Sotiroudis G.T., Ζoumpoulakis P., Arbez-Gindre C., Bouzouita N., Sotiroudis T. G. “Melanin and humic acid-like polymer complex from olive mill waste waters. Part I. Isolation and characterization”, Food chem., 2016, 203, 540-547; IF=7.514 (2021)
  • Sleiman M.H., Csonka R., Arbez-Gindre C., Heropoulos G. A., Calogeropoulou T., Signorelli M., Schiraldi A., Steele B. R., Fessas D., Micha-Screttas M., “Binding and stabilisation effects of glycodendritic compounds with peanut agglutinin”, International Journal of Biological Macromolecules, 2015, 80, 692–701; IF= 6.953 (2021)
  • Ramaswamy S., Sleiman M.H., Masuyer G., Arbez-Gindre C., Micha-Screttas M., Calogeropoulou T., Steele B.R. and Acharya K. R., “Structural basis of multivalent galactose-based dendrimer recognition by human galectin-7”, FEBS Journal, 2015, 282, 372–387; IF=5.542 (2021)
  • Kostas I.D., Tenchiu A.-C., Arbez-Gindre C., Psycharis V., Raptopoulou C.P., “Room-temperature Suzuki-Miyaura coupling of aryl bromides with phenylboronic acid catalyzed by a palladium complex with an inexpensive nitrogen-containing bis(phosphinite) ligand” Catal. Commun., 2014, 51, 15-18; IF=3.56 (2020)
  • Claudel E., Arbez-Gindre C., Berl V. and. Lepoittevin J.-P, “An efficient Hemi-synthesis of 20- and 21-[13-C] labelled Cortexolone: A model for the Study of Skin Sensitization to Corticosteroids”, Synthesis 2009, 20, 3391-3398; IF = 3.157 (2021)
  • Arbez-Gindre C., Steele B.R., Heropoulos G.A., Screttas C.G, Communal J.E., Blau W.J, Ledoux-Rak I., “A facile organolithium route to ferrocene-based triarylmethyl dyes with substantial near IR and NLO properties”, J. Organomet. Chem. 2005, 690, 1620-1626; IF=2.22 (2020-2021)
  • Arbez-Gindre C., Berl V., and Lepoittevin J.-P., “Air oxidation of 17-hydroxycorticosteroids catalyzed by cupric acetate: formation of hemiacetal dimmers”, Steroids 2003, 68, 361-365; IF=2.668 (2021)
  • Calaminici P., Jug K., Koster A.M., Arbez-Gindre C. and Screttas C.G., “Mechanism for large first hyperpolarisabilities of phosphonic acid stilbene derivatives”, J. Comput. Chem. 2002, 23, 291-297; IF=3.34 (2020)
  • Paci B; Schmidt C., Fiorini C., Nunzi J.M., Arbez-Gindre C. and Screttas C.G., “Nonlinear optical properties of push-pull stilbenes based on a strong carbocation acceptor moiety”, J. Chem. Physics 1999, 111, 7486-7492; IF=3.488 (2021)
  • Arbez-Gindre C., Berl V., and Lepoittevin J.-P., “Methyl exchange on silicon during the addition of methyl magnesium iodide to cyanohydrin-O-silyl ether”, J. Chem. Soc., Chem. Comm., 1999, 431-432; IF=6.222 (2021)
  • Arbez-Gindre C., Screttas C.G., Fiorini C., Schmidt C. and Nunzi J.M., “Organolithium reagents bearing nonlinear optical chromophores. Synthesis of triarylmethane dyes”, Tetrahedron Lett. 1999, Vol. 40, 7413-7416; IF= 2.25 (2020)
  • Matura M., Lepoittevin J.-P., Arbez-Gindre C., Goossens A.,“Testing with corticosteroid aldehydes in corticosteroid sensitive subjects (preliminary results)”, Contact Derm., 1998, 38, 106-108; IF=6.6 /Q2 (2021-2022)





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