Research

Chemical Innovation

Apart from its objectives as a storage and handling center, HSMC is a center of excellence for chemical innovation. Top-notch chemical synthesis is one of our main concerns in HSMC. Groups working in the total synthesis of natural products, medicinal chemistry, and development of catalytic systems provide an ideal environment for the synthesis of novel chemical entities that can further enrich our chemical libraries.

 

Total Synthesis of Natural Products

Total synthesis of naturally occurring compounds with complex molecular architectures, useful biological properties and interesting mechanism of biological action, is under our constant interest. (I would recommend a small pop up with more details in every category)

  • Alkaloids (pyridones, pyrrole-imidazole, pyrroles, indoles)
  • Sesquiterpenoids
  • Nucleosides

Discovery and Development of Novel Reactions-Catalysis

New reaction discovery is the most important research activity in the area of organic chemistry, and target-directed reaction discovery is one of the best strategies for identifying important transformations.

Under this general area we are especially interested on:

  • CH-activation: the late stage functionalization of heterocycles and b. for selective late stage oxidations of complex molecules.
  • Photocatalysis: Selective photo-oxidation of organic compounds with Polyoxometalates (POMs) and molecular oxygen.
  • Catalysis: a) Green Organic redox transformations catalyzed by Metal Nanoparticles (NPs) and b) Organo-catalytic methodologies and mechanistic studies οn the synthesis of herocyclic compounds (i.e. pyrroles, pyrazoles, pyridines and imidazoles).

Medicinal Chemistry Projects

Current medicinal chemistry projects involve the development of bioactive compounds as modulators of protein function for the study of various biological processes and the development of novel therapeutics. For example:

  • Enzyme inhibitors: inositol derivatives, modified nucleosides, carbohydrate derivatives, heterocycles, acridones
  • Inhibitors of protein-protein interactions: a) Phenoxazines as DKK1/LRP6 interaction inhibitors for the treatment of Alzheimer’s disease and related neurodegenerative tauopathies. b)  Pyrrole-2,5-diones as LMP1/TRAF interaction inhibitors
  • Hybrid compounds for targeted drug delivery: Peptides and steroids have been selected to deliver classical chemotherapeutic drugs (nitrogen mustards, platinum complexes, antimetabolites, cytotoxic natural products) to cancer cells in order to minimize systemic toxicity and increase their therapeutic effect.

Modification of complex molecules

A team of experts in organic synthesis and catalysis provides solutions for the late stage modifications of important compounds. In collaboration with the inventors and teams working on molecular modeling, HSMC synthetic groups can try to modify specific regions of your “lead” compounds to optimize their biological properties. (photo should be a collage of molecular models with some enzymes)

Publications

Indicative publications from every area of our research are highlighted below

Total synthesis of natural products

  1. V. Demertzidou, A. L. Zografos “Platinum-catalyzed cycloisomerizations of a common enyne: a divergent entry to cyclopropane sesquiterpenoids” Org. Biomol. Chem. 2016, 14, 6942.
  2. E. E. Anagnostaki, V. Demertzidou, A. L. Zografos* “Divergent Pathways to Furosesquiterpenes. First Total Syntheses of (+)-Zedoarol and (Rac)-Gweicurculactone” Chem. Comm. 2015, 51, 2364
  3. E. Anagnostaki, A. Zografos* “A non-natural elemane as the stepping stone for the synthesis of germacrane and guaiane sesquiterpenes” Org. Lett. 2013, 15, 152.
  4. A. Fotiadou, A. Zografos* “Accessing the structural diversity of pyridone alkaloids: Total synthesis of Rac-citridone A” Org. Lett. 2011, 13, 4592.
  5. A Chatzimpaloglou, MP Yavropoulou, KE Rooij, R Biedermann, U Mueller, S Kaskel, V Sarli, ‘’Total synthesis and biological activity of the proposed structure of phaeosphaeride A’’, J. Org. Chem. 2012, 77, 9659.
  6. A Chatzimpaloglou, M Kolosov, TK Eckols, DJ Tweardy, V Sarli, ‘’Synthetic and biological studies of phaeosphaerides’’ J. Org. Chem. 2014, 79, 4043.

Discovery and Development of novel reactions

  1. V. P. Demertzidou, S. Pappa, V. Sarli, A. L. Zografos “Regioselective ene-type allylic chlorination of electron rich alkenes by activated DMSO” J. Org. Chem. 2017, 82, 8710
  2. T. Katsina, E. E. Anagnostaki, F. Mitsa, V. Sarli, A. L. Zografos ” Palladium-Catalyzed Direct Alkenylation of 4-Hydroxy-2-pyridones” RSC Advances, 2016, 6, 6978.
  3. E. E. Anagnostaki, A. D. Fotiadou, V. Demertzidou, A. L. Zografos* “Palladium Catalyzed C-3 Arylation of 4-hydroxy-2-Pyridones” Chem. Commun. 2014, 50, 6879.
  4. A. Fotiadou, A. Zografos* “Electrocyclization of oxatrienes in the construction of structurally complex pyranopyridones” Org. Lett. 2012, 14, 5664.
  5. S. Fountoulaki, V. Daikopoulou, P.L. Gkizis, I. Tamiolakis, G.S. Armatas, I.N. Lykakis* “Mechanistic studies of the reduction of nitroarenes by NaBH4 or hydrosilanes catalyzed by supported gold nanoparticles.” ACS Catalysis 2014, 4, 3504.
  6. D. Andreou, D. Iordanidou, I. Tamiolakis, G.S. Armatas, I.N. Lykakis* “Reduction of nitroarenes into arylamines and N-aryl hydroxylamines via activation of NaBH4 and ammonia-borane complexes by Ag/TiO2 Catalyst” Nanomaterials, 2016, 6, 54.
  7. S. Fountoulaki, P.L. Gkizis, T.S. Symeonidis, E. Kaminioti, A. Karina, I. Tamiolakis, G.S. Armatas, I. N. Lykakis* “Titania-Supported Gold Nanoparticles Catalyze the Selective Oxidation of Amines into Nitroso Compounds in the Presence of Hydrogen Peroxide” Adv. Synth. Catal., 2016, 358, 1500.
  8. M. Kallitsakis, E. Loukopoulos, A. Abdul-Sada, G.J. Tizzard, S. J.; Coles, G. S. Kostakis, I. N. Lykakis* “A copper-benzotriazole based coordination polymer catalyzes the efficient one-pot synthesis of (N’-substituted)-hydrazo-4aryl-1,4-dihydropyridines from azines” Adv. Synth. Catal. 2017, 359, 138.
  9. E. Charistoudi, M. G. Kallitsakis, I. Charisteidis, K. S. Triantafyllidis, I. N. Lykakis* “Selective reduction of azines to benzyl hydrazones with NaBH4 catalyzed by mesoporous silica supported silver nanoparticles: A catalytic route towards pyrazole synthesis“ Adv. Synth. Catal. 2017, 359, 2949.
  10. T. S. Symeonidis, A. Athanasoulis, R. Ishii, Y. Uozumi, Y.M.A. Yamada, I. N. Lykakis* “Photocatalytic aerobic oxidation of alkenes into epoxides or chlorohydrins promoted by polymer supported decatungstate catalyst“. ChemPhotoChem. 2017, 10, 479.
  11. M. G. Kallitsakis, P. Tancini, M. Dixit, G. Mpourmpakis, I. N. Lykakis* “Mechanistic studies on the Michael addition of amines and hydrazines to nitrostyrenes: Nitroalkane elimination via a retro-aza-Henry type process” J. Org. Chem. 2018, 83, 1176.
  12. D. Andreou, M. G. Kallitsakis, E. Loukopoulos, C. Gabriel, G. E. Kostakis, I.N. Lykakis* “Copper-promoted regioselective synthesis of polysubstituted pyrroles from aldehydes, amines and nitroalkenes via 1,2-phenyl/alkyl migration” J. Org. Chem. 2018, 83, 2104.
  13. M Grammatikopoulou, S Thysiadis, V Sarli, ‘’Gold-catalyzed spiro-N,O-ketal synthesis’’, Org. Biomοl. Chem. 2015, 13, 1169.

Medicinal Chemistry Projects

  1. I. Sigala, G. Ganidis, S. Thysiadis, A. L. Zografos, T. Giannakouros, V. Sarli, E. Nikolakaki, “Lynamicin D an Antimicrobial Natural Product Affects Splicing by Inducing the Expression of SR Protein Kinase” Bioorg. Med. Chem. 2017, 25, 1622
  2. E. Kontogiannidou, D. A. Andreadis, A. L. Zografos, H. Nazar, P. Klepetsanis, S. M. van der Merwe, D. G. Fatouros “Ex vivo buccal drug delivery of ropinirole hydrochloride in the precence of permeation enhancers: the effect of charge” Pharm. Develop. Technol. 2017, 22, 1017
  3. Z. V. Peitsinis, Α. G. Mitrakas, E. A. Nakiou, D. A. Melidou, D. Kalamida, C. Kakouratos, M. I. Koukourakis, A. E. Koumbis, “Trachycladines and Analogues: Synthesis and Evaluation of Anticancer Activity”, ChemMedChem, 2017, 12, 448.
  4. M. Pasolli, K. Dafnopoulos, N.-P. Andreou, P. S. Gritzapis, M. Koffa, A. E. Koumbis, G. Psomas, K. C. Fylaktakidou, “Pyridine and p-Nitrophenyl Oxime Esters with Possible Photochemotherapeutic Activity: Synthesis, DNA Photocleavage and DNA Binding Studies”, Molecules 2016, 21, Νο 864.
  5. N.-P. Andreou, K. Dafnopoulos, C. Tortopidis, A. E. Koumbis, M. Koffa, G. Psomas, K. C. Fylaktakidou, “Alkyl and Aryl Sulfonyl p-Pyridine Ethanone Oximes are Efficient DNA Photo-Cleavage Agents”, J. Photochem. Photobiol. B 2016, 158, 30.
  6. A. Papastergiou, S. Perontsis, P. Gritzapis, A. E. Koumbis, M. Koffa, G. Psomas, K. C. Fylaktakidou, “Evaluation of O-Αlkyl and Αryl Sulfonyl Aromatic and Heteroaromatic Amidoximes as Novel Potent DNA Photo-cleavers”, Photochem. Photobiol. Sci. 2016, 15, 351.
  7. V. Konieczny, J. G. Stefanakis, E. D. Sitsanidis, N.-A. T. Ioannidou, N. V. Papadopoulos, K. C. Fylaktakidou, C. W. Taylor, A. E. Koumbis, “Synthesis of Inositol Phosphate-based Competitive Antagonists of Inositol 1,4,5-Trisphosphate Receptors”, Org. Biom. Chem. 2016, 14, 2504.
  8. S. S. Kotoulas, V. V. Kojić, G. M. Bogdanović, A. E. Koumbis, “Synthesis of Novel Pyrimidine Apiothionucleosides and in vitro Evaluation of their Cytotoxicity”, Tetrahedron 2015, 71, 3396.
  9. P. Karamtzioti, A. Papastergiou, J. G. Stefanakis, A. E. Koumbis, I. Anastasiou, M. Koffa, K. C. Fylaktakidou, “O-Benzoyl Pyridine Aldoxime and Amidoxime Derivatives: Novel Efficient DNA Photo-cleavage Agents”, MedChemComm 2015, 6, 719.
  10. Z. V. Peitsinis, D. A. Melidou, J. G. Stefanakis, H. Evgenidou, A. E. Koumbis, “A Versatile Total Synthesis of Trachycladines A and B and Their Analogues”, Eur. J. Org. Chem. 2014, 8160.
  11. I. Doulou, C. Kontogiorgis, A. E. Koumbis, E. Evgenidou, D. Hadjipavlou-Litina, K. C. Fylaktakidou, “Synthesis of Stable Aromatic and Heteroaromatic Sulfonyl-amidoximes and Evaluation of their Antioxidant and Lipid Peroxidation Activity”, Eur. J. Med. Chem. 2014, 80, 145.
  12. S. S. Kotoulas, V. V. Kojić, G. M. Bogdanović, A. E. Koumbis, “Synthesis and Cytotoxic Evaluation of Novel Pyrimidine Deoxyapiothionucleosides”, Bioorg. Med. Chem. Lett. 2013, 23, 3364.
  13. A.-A. C. Varvogli, K. C. Fylaktakidou, T. Farmaki, J. G. Stefanakis, A. E. Koumbis, “Versatile Synthesis of 1-O-(ω-Aminolauryl)-I(4,5)P2”, Eur. J. Org. Chem. 2012, 5855.
  14. K. C. Fylaktakidou, C. D. Duarte, R. Jogireddy, A. E. Koumbis, C. Nicolau, J.-M. Lehn, “Polyphosphates and Pyrophosphates of Pentopyranoses and Pentofuranoses as Allosteric Effectors of Human Hemoglobin: Synthesis, Molecular Recognition, and Oxygen Release”, ChemMedChem, 2011, 6, 1495.
  15. A. E. Koumbis, C. D. Duarte, C. Nicolau, J.-M. Lehn, “Tetrakisphosphates and Bispyrophosphates of myo-Inositol Derivatives as Allosteric Effectors of Human Hemoglobin: Synthesis, Molecular Recognition, and Oxygen Release”, ChemMedChem, 2011, 6, 169.
  16. K. C. Fylaktakidou, C. D. Duarte, A. E. Koumbis, C. Nicolau, J.-M. Lehn, “Polyphosphates and Pyrophosphates of Hexopyranoses as Allosteric Effectors of Human Hemoglobin: Synthesis, Molecular Recognition, and Effect on Oxygen Release”, ChemMedChem 2011, 6, 153.
  17. Tcherniuk, S. Deshayes, V. Sarli, G. Divita, A. Abrieu, “UA62784 is a cytotoxic inhibitor of microtubules, not CENP-E”, Chem. Biol. 2011, 18, 631.
  18. A. Voultsiadou, V. Sarli, “Recent Advances of Kinesin Motor Inhibitors and their Clinical Progress, Rev. Recent Clin. Trials”, 2011, 6, 271.
  19. S. Mpousis, S. Thysiadis, N. Avramidis, S. Katsamakas, S. Efthimiopoulos, V. Sarli, “Synthesis and evaluation of gallocyanine dyes as potential agents for the treatment of Alzheimer’s disease and related neurodegenerative tauopathies”,  Eur. J. Med. Chem. 2016, 108, 28.
  20. S. Thysiadis, S. Mpousis, N. Avramidis, S. Katsamakas, A. Balomenos, R. Remelli, S. Efthimiopoulos, V. Sarli, “Discovery of Novel Phenoxazinone Derivatives as DKK1/LRP6 Interaction Inhibitors”, Bioorg. Med. Chem. 2016, 24, 1014.
  21. S. Katsamakas, A.L. Zografos, V. Sarli, “Advances of Phenoxazines: Synthesis, Reactivity and Their Medicinal Applications”, Curr. Med. Chem. 2016, 23, 2972.
  22. D. Trafalis, E. Geromichalou, P. Dalezis, N. Nikoleousakos, V. Sarli. “Synthesis and evaluation of new steroidal lactam conjugates with aniline mustards as potential antileukemic therapeutics”, Steroids, 2016, 115, 1.
  23. S. Katsamakas, T. Chatzisideri, S. Thysiadis, V. Sarli. “ RGD-mediated delivery of small-molecule drugs”, Future Med. Chem. 2017, 9, 579.
  24. D.T. Trafalis, A. Polonifi, P. Dalezis, N. Nikoleousakos, S. Katsamakas, V. Sarli. “Targeting on poly(ADP-ribose) polymerase activity with DNA-damaging hybrid lactam-steroid alkylators in wild-type and BRCA1-mutated ovarian cancer cells”, Chem. Biol. Drug Des. 2017, 90, 854.
  25. E. Tsovaltzi,  E. Malamidou-Xenikaki,  P. Dalezis,  A. Hatzidimitriou,  D. Trafalis,  T. Lazarides, V. Sarli  “Synthesis and Analysis of the Anticancer Activity of Ru(II) Complexes Incorporating 2-Hydroxymethylidene-indene-1,3-diones Ligands”, New J. Chem, 2017, 41, 10438.
  26. T. Chatzisideri, S. Thysiadis, S. Katsamakas, P. Dalezis, I. Sigala, T. Lazarides, E. Nikolakaki, D. Trafalis, O.A. Gederaas, M. Lindgren, V. Sarli, “Synthesis and Biological Evaluation of a Platinum(II)-c(RGDyK) Conjugate for Integrin-Targeted Photodynamic Therapy”, Eur. J. Med. Chem. 2017, 141, 221.
  27. Thysiadis, S. Katsamakas, P. Dalezis, T. Chatzisideri, D. Trafalis, V. Sarli, “Novel c(RGDyK)-based Conjugates of POPAM and 5-FU for Integrin-Targeted Cancer Therapy”, Future Med. Chem. 2017, 9, 2181.
  28. S. Thysiadis, S. Katsamakas, S. Mpousis, N. Avramidis, S. Efthimiopoulos, V. Sarli, “Design and synthesis of gallocyanine inhibitors of DKK1/LRP6 interactions for treatment of Alzheimer’s disease”, Bioorg Chem. 2018, 80, 230.