Institute of Chemical Biology - National Hellenic Research Foundation

Synthetic and Medicinal Chemistry
Dr. George E. Magoulas | Associate Researcher, Group Leader

About Team Collaborations Publications

Research Directions - Aims

The group focuses on the design and synthesis of biologically active molecules suitable for Structure-activity relationship (SAR) studies against a wide range of pathologies with high impact on society such as cancer and neglected tropical diseases. For this purpose, apart from employing modern synthetic methodologies, the group also embraces the philosophy of green chemistry utilizing microwave-assisted synthesis or multi-component reactions (MCR) which offers simplicity, versatility and high atom economy. Furthermore, Dr. G.E. Magoulas has created an extensive network of collaborators in Greece and abroad through previous research projects and COST Actions.

Project 1: Design and synthesis of heterocyclic compounds against Malaria, Leishmaniasis, Chagas diseases and Human African Trypanosomiasis

Neglected Tropical Diseases (NTDs) represent a group of 20 pathologies that are classified by the World Health Organization (WHO) as such due to their medicinal and societal impact. They are endemic in 149 countries, mainly in tropical and subtropical areas, and are highly associated with poverty. These diseases affect hundreds of millions of people worldwide with significant morbidity and/or mortality. In addition, they are neglected by research since most of the drugs currently in use for their treatment, are old with various limitations such as low efficacy, high toxicity, emergence of parasite resistance, difficulties in patient compliance, and high cost.

The group, through COST action “One Health drugs against parasitic vector borne diseases in Europe and beyond”, aspires to contribute to the enrichment of compound libraries through the synthesis of new heterocyclic compounds as potent anti-malarial and anti-trypanosomatid agents.

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Project 2: Design and synthesis of lignans to combat Triple-Negative Breast Cancer (TNBC)

Lignans comprise a large family of optically active compounds isolated from plant extracts sharing a common feature, that is, two phenylpropanoid units coupled through the central carbons of their propane side chains. In plants, the biosynthesis of lignans is probably realized through a peroxidase enzyme-catalyzed free radical dimerization of hydroxy caffeic acid (HCA) derivatives or of their reduced analogs. These polyphenolic compounds exhibit a wide range of biological activities including antiapoptotic and cytotoxic actions among others. Capitalizing on our previous findings that compounds 1 and 2 showed interesting antiproliferative activity against MDA-MB-231 cell line, the group focuses on the synthesis of new hybrid compounds of the lignan-type with improved biological activity and pharmacokinetic properties.

Technology Transfer

Patents

PCT/EP2021/075969, 21/09/2021 “Compound for use in the treatment of protozoal diseases and process for production of said compound”. Applicant: QuadrEL Srl. Inventors: Calogeropoulou, T. Prousis, K.C., Roussaki, M., Magoulas, G.E., Fotopoulou T.
GR 20200100577, 22/09/2020 “Compound for use in the treatment of protozoal diseases and process for production of said compound”. Applicant: National Hellenic Research Foundation. Inventors: Calogeropoulou, T. Prousis, K.C., Roussaki, M., Magoulas, G.E., Fotopoulou T.

Group Structure and Personnel

Dr. George E. Magoulas, Associate Researcher, Group Leader
Dr. Georgia Antonopoulou, Scientific Technical personnel

Collaborations

National

Research Director Dr. T. Calogeropoulou, ICB-NHRF
Prof. N. Karamanos, Department of Chemistry, University of Patras
Research Director Dr. M. Koufaki, ICB-NHRF
Research Director Dr. N. Chondrogianni, ICB-NHRF
Research Director Dr. I. Kostas, ICB-NHRF

International

Prof. M.L. Bolognesi, Department of Pharmacy and Biotechnology, University of Bologna, Italy
Prof. 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
Prof. L.A. Soares Romeiro, Department of Pharmacy, University of Brasilia, Brazil

Publications

ORCID: https://orcid.org/0000-0001-8944-1635
Google Scholar: https://scholar.google.com/citations?hl=el&user=83iCr3MAAAAJ

L.F. Nunes Lemes, G.E. Magoulas, A. Souza de Oliveira, E. Barrias, L. de Camargo Nascente, R. Granado, S. Teixeira de Macedo Silva, N. Assimomytis, W. de Souza, M.L. Bolognesi, L.A. Soares Romeiro, T. Calogeropoulou. Valorizing constituents of cashew nut shell liquid towards the sustainable development of new drugs against Chagas disease. ACS Infect. Dis. 2023, 9, 1334-1345.
https://doi.org/10.1021/acsinfecdis.3c00076
M. Roussaki, G.E. Magoulas, T. Fotopoulou, N. Santarem, E. Barrias, I. Pöhner, S. Luelmo, P. Afroudakis, K. Georgikopoulou, P.T. Nevado, J. Eick, E. Bifeld, M.J. Corral, M.D. Jiménez-Antón, B. Ellinger, M. Kuzikov, I. Fragiadaki, E. Scoulica, S. Gul, J. Clos, K.C. Prousis, J.J. Torrado, J.M. Alunda, R.C. Wade, W. de Souza, A.C. da Silva, T. Calogeropoulou. Design, synthesis and biological evaluation of antiparasitic dinitroaniline-ether phospholipid hybrids. Bioorg. Chem. 2023, 138, 106615.
https://doi.org/10.1016/j.bioorg.2023.106615
G.E. Magoulas*. Ageladine A, a Bromopyrrole Alkaloid from the Marine Sponge Agelas nakamurai. Compounds, 2023, 3, 107-121.
https://doi.org/10.3390/compounds3010010
A. Venturelli, L. Tagliazucchi, C. Lima, F. Venuti, G. Malpezzi, G.E. Magoulas, N. Santarem, T. Calogeropoulou, A. Cordeiro-da-Silva, M.P. Costi. Current Treatments to Control African Trypanosomiasis and One Health Perspective, Microorganisms, 2022, 10, 1298.
https://doi.org/10.3390/microorganisms10071298
G.E. Magoulas, P. Afroudakis, K. Georgikopoulou, M. Roussaki, C. Borsari, T. Fotopoulou, N. Santarem, E. Barrias, P. Tejera 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. Design, Synthesis and Antiparasitic Evaluation of Click Phospholipids. Molecules, 2021, 26, 4204.
https://doi.org/10.3390/molecules26144204
K. Grafanaki, I. Skeparnias, C.K. Kontos, D. Anastasakis, A. Korfiati, G. Kyriakopoulos, K. Theofilatos, S. Mavroudi, G. Magoulas, D. Papaioannou, A. Scorilas, C. Stathopoulos, D. Drainas. Pharmacoepigenomics circuits induced by a novel retinoid-polyamine conjugate in human immortalized keratinocytes. Pharmacogenomics J. 2021,
https://doi.org/10.1038/s41397-021-00241-9
G.E. Magoulas, L. Kalopetridou, Ana Ćirić, Eftichia Kritsi, P. Kouka, P. Zoumpoulakis, N. Chondrogianni, M. Soković, K.C. Prousis, T. Calogeropoulou. Synthesis, biological evaluation and QSAR studies of new thieno[2,3-d]pyrimidin-4(3H)-one derivatives as antimicrobial and antifungal agents. Bioorg. Chem. 2021, 106, Article 104509.
https://doi.org/10.1016/j.bioorg.2020.104509
E. Chazapi, G.E. Magoulas, K.C. Prousis, T. Calogeropoulou. Phospholipid analogues as chemotherapeutic agents against trypanosomatids. Curr. Pharm. Des. 2021, 27, 1790-1806.
10.2174/1381612826666201210115340
G.E. Magoulas, T. Tsigkou, L. Skondra, M. Lamprou, P. Tsoukala, V. Kokkinogouli, E. Pantazaka, D. Papaioannou, C.M. Athanassopoulos, E. Papadimitriou. Synthesis of novel artemisinin dimers with polyamine linkers and evaluation of their potential as anticancer agents. Bioorg. Med. Chem. 2017, 25, 3756-3767.
https://doi.org/10.1016/j.bmc.2017.05.018
K. Koutsiouki, A. Angelopoulou, E. Ioannou, E. Voulgari; A. Sergides, G.E. Magoulas, A. Bakandritsos, K. Avgoustakis. TAT peptide-conjugated magnetic PLA-PEG nanocapsules for the targeted delivery of paclitaxel: in vitro and cell studies. AAPS PharmSciTech., 2017, 18, 769-781.
https://doi.org/10.1208/s12249-016-0560-9
G.E. Magoulas*, A. Rigopoulos, Z. Piperigkou, C. Gialeli, N.K. Karamanos, A.N. Troganis, A. Chrissanthopoulos, G. Maroulis, D. Papaioannou. Synthesis and antiproliferative activity of two diastereomeric lignan amides serving as dimeric caffeic acid-L-DOPA hybrids. Bioorg. Chem. 2016, 66, 132-144.
https://doi.org/10.1016/j.bioorg.2016.04.003
S. Stoica, G.E. Magoulas, A. Antoniou, A. Cassar, S. Suleiman, L. Gatt, D. Papaioannou, C.M. Athanassopoulos, P. Schembri-Wismayer. Synthesis of minoxidil conjugates and their evaluation as HL-60 differentiation agents. Bioorg. Med. Chem. Lett. 2016, 26, 1145-1150.
https://doi.org/10.1016/j.bmcl.2016.01.048
T. Petridis, D. Giannakopoulou, V. Stamatopoulou, K. Grafanaki, C.G. Kostopoulos, H. Papadaki, C.J. Malavaki, N.K. Karamanos, S. Douroumi, D. Papachristou, G.E. Magoulas, D. Papaioannou, D. Drainas. Investigation on toxicity and teratogenenicity in rats of a retinoid-polyamine conjugate with potent anti-inflammatory properties. Birth Defects Res. B Dev. Reprod. Toxicol. 2016, 107, 32-44.
10.1002/bdrb.21170

2015-2002

G.E. Magoulas, M. Bantzi, D. Messari, E. Voulgari, C. Gialeli, D. Barbouri, A. Giannis, N.K. Karamanos, D. Papaioannou, K. Avgoustakis. Synthesis and Εvaluation of Αnticancer Αctivity in Cells of Novel Stoichiometric Pegylated Fullerene-Doxorubicin conjugates. Pharm. Res. 2015, 32, 1676-1693.
https://doi.org/10.1007/s11095-014-1566-1
S.E. Bariamis, G.E. Magoulas, K. Grafanaki, E. Pontiki, T. Tsegenidis, C.M. Athanassopoulos, D. Papaioannou, D. Hadjipavlou-Litina. Synthesis and Biological Εvaluation of new C-10 Substituted Dithranol Pleiotropic Hybrids. Bioorg. Med. Chem. 2015, 23, 7251-7263.
https://doi.org/10.1016/j.bmc.2015.10.022
O.N. Kostopoulou, G.E. Magoulas, G.Papadopoulos, A. Mouzaki, G.P. Dinos, D. Papaioannou, D.L. Kalpaxis. Synthesis and Evaluation of Chloramphenicol Homodimers: Effect on Peptide-Bond Formation, Antimicrobial Activity, and Toxicity against Bacterial Strains and Healthy or Leukemic Human Cells. PLOS ONE. 2015, 10(8) e0134526.
10.1371/journal.pone.0134526
G.E. Magoulas, O.N. Kostopoulou, T. Garnelis, C.M. Athanassopoulos, G.G. Kournoutou, M. Leotsinidis, Synthesis and antimicrobial activity of chloramphenicol-polyamine conjugates. Bioorg. Med. Chem. 2015, 23, 3163-3174.
https://doi.org/10.1016/j.bmc.2015.04.069
G.E. Magoulas, D. Papaioannou. Bioinspired syntheses of dimeric hydroxycinnamic acids (lignans) and hybrids, using phenol oxidative coupling as key reaction, and medicinal significance thereof. Molecules, 2014, 19, 19769-19835.
https://doi.org/10.3390/molecules191219769
O. N. Kostopoulou, E.C. Kouvela, G.E. Magoulas, T. Garnelis, I. Panagoulias, M. Rodi, G. Papadopoulos, A. Mouzaki, G. P. Dinos, D. Papaioannou, D.L. Kalpaxis Conjugation with polyamines enhances the antibacterial and anticancer activity of chloramphenicol. Nucleic Acids Res. 2014, 42, 8621-8634.
10.1093/nar/gku539
D. Hadjipavlou-Litina, G.E. Magoulas, S.E. Bariamis, Z. Tsimali, K. Avgoustakis, C.A. Kontogiorgis, C.M. Athanassopoulos, D. Papaioannou. Synthesis and Evaluation of Antioxidative Potential of Minoxidil-Polyamine Conjugates. Biochimie. 2013, 95, 1437-1449.
https://doi.org/10.1016/j.biochi.2013.03.009
D. Vourtsis, M. Lamprou, E. Sadikoglou, A. Giannou, O. Theodorakopoulou, E. Sarrou, G.E. Magoulas, S.E. Bariamis, C.M. Athanassopoulos, D. Drainas, D. Papaioannou, E. Papadimitriou. Effect of an all-trans-retinoic acid conjugate with spermine on viability of human prostate cancer and endothelial cells in vitro and angiogenesis in vivo. Eur. J. Pharmacol. 2013, 698, 122-130.
https://doi.org/10.1016/j.ejphar.2012.11.007
G.E. Magoulas, Th. Garnelis, C.M. Athanassopoulos, D. Papaioannou, G. Mattheolabakis, K. Avgoustakis, D. Hadjipavlou-Litina. Synthesis and Antioxidative Activity of Novel Fullerene-Polyamine Conjugates. Tetrahedron. 2012, 68, 7041-7049.
https://doi.org/10.1016/j.tet.2012.06.066
O.N. Kostopoulou, T.G. Kourelis, P. Mamos, G.E. Magoulas, D.L. Kalpaxis. Insights into the chloramphenicol inhibition effect on peptidyltransferase activity, using two new analogues of the drug. The Open Enz. Inh. J. 2011, 4, 1-10.
10.2174/1874940201104010001
G.E. Magoulas, S.E. Bariamis, C.M. Athanassopoulos, D. Papaioannou, G. Maroulis, A. Haskopoulos, P. Dedes, M. Krokidis, N.K. Karamanos, D. Kletsas. Efficient Total Syntheses, Antiproliferative Activity and Theoretical Characterization of Acitretin-Type Retinoids with Changes in the Lipophilic Part. Eur. J. Med. Chem., 2011, 46, 721-737.
https://doi.org/10.1016/j.ejmech.2010.12.008
D. Hatjipavlou-Litina, G.E. Magoulas, S.E. Bariamis, D. Drainas, D. Papaioannou. Does conjugation of antioxidants improve their antioxidative/anti-inflammatory potential? Biorg. Med. Chem. 2010, 18, 8204-8217.
https://doi.org/10.1016/j.bmc.2010.10.012
G.E. Magoulas, S.E. Bariamis, C.M. Athanassopoulos, D. Papaioannou. Synthetic studies towards the development of novel minoxidil analogs and conjugates with polyamines. Tetrahedron Lett., 2010, 51, 1989-1993.
https://doi.org/10.1016/j.tetlet.2010.02.037
D. Hatjipavlou-Litina, G.E. Magoulas, M. Krokidis, D. Papaioannou. Syntheses and evaluation of the antioxidant activity of acitretin analogs with amide bond(s) in the polyene spacer. Eur. J. Med. Chem. 2010, 45, 298-310.
https://doi.org/10.1016/j.ejmech.2009.10.012
S.E. Bariamis, G.E. Magoulas, C.M. Athanassopoulos, D. Papaioannou, M.J. Manos, V. Nastopoulos. (2E,4E,6E)-3-methyl-7-(pyren-1-yl)octa-2,4,6,-trienoic acid. Acta Cryst. E. 2009, E65, o2580.
10.1107/S1600536809038409
E. Sadikoglou, G. Magoulas, C. Theodoropoulou, C.M. Athanassopoulos, E. Giannopoulou, O. Theodorakopoulou, D. Drainas, D. Papaioannou, E. Papadimitriou. Effect of conjugates of all-trans retinoic acid and shorter polyene chain analogues with amino acids on prostate cancer cell growth. Eur. J. Med. Chem., 2009, 44, 3175-3187.
https://doi.org/10.1016/j.ejmech.2009.03.029
G. Magoulas, D. Papaioannou, E. Papadimou, D. Drainas. Preparation of spermine conjugates with acidic retinoids with potent ribonuclease P inhibitory activity. Eur. J. Med. Chem., 2009, 44, 2689-2695.
https://doi.org/10.1016/j.ejmech.2009.01.001
C.M. Athanassopoulos, T. Garnelis, G. Magoulas, D. Papaioannou. Efficient Synthesis of Polyamines Bearing 1H-Tetrazol-5-yl Units on Their Amino Functions. Synthesis, 2006, 18, 3134-3140.
10.1055/s-2006-942502
G. Magoulas, D. Papaioannou. Synthetic studies towards the development of a novel class of acitretin-type retinoids. Arkivoc 2003, (vi), 213–227.
https://doi.org/10.3998/ark.5550190.0004.623
Μ. Militsopoulou, N. Tsiakopoulos, C. Chochos, G. Magoulas, D. Papaioannou. Simple Synthesis of cyclic polyamines using selectively N–tritylated polyamines and dicarboxylic acids as bridging elements. Tetrahedron Lett. 2002, 43, 2593–2596.
https://doi.org/10.1016/S0040-4039(02)00335-0