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Professor Michael Kassiou


Contact Details

Professor of Medicinal Chemistry
Room 516
Brain and Mind Research Institute and
School of Chemistry, Building F11
The University of Sydney
NSW, 2006, Australia
E: michael.kassiou@sydney.edu.au
T: +61-2-9351-2745
F: +61-2-9351-3329
W: http://sydney.edu.au/science/chemistry/~kassiou

Career Profile

  • BSc (Hons), University of New South Wales, 1988
  • PhD, University of New South Wales, 1992
  • Visiting Scientist, The Johns Hopkins Medical Institutes USA, 1993
  • Visiting Scientist, SHFJ-CEA Life Sciences group France, 1993
  • NIH Fogarty Fellow, The National Institute on Drug Abuse USA, 1996

Areas of Research

  • Medicinal Chemistry and Drug Discovery
  • Structure-activity relationships of CNS bioactive molecules
  • Rationale CNS drug design and evaluation
  • Heterocyclic Chemistry

Research

Research in my group is interdisciplinary and built around the key themes of medicinal chemistry and drug discovery. In this domain understanding drug-protein and drug-binding site interactions is a key component which allows us to obtain structure-activity relationships of bioactive CNS molecules and therefore the rational design of more efficacious treatments for diseases of the brain. In addition by using molecular imaging techniques within these fields we are able to better understand the living brain in normal and diseased states through in vivo studies.

For current research activities and opportunities please visit our home page: http://www.chem.usyd.edu.au/~kassiou

Publications (2009 to 2013)

  1. Banister, SD; Manoli, M and Kassiou, M. The development of radiotracers for imaging sigma (σ) receptors in the central nervous system (CNS) using positron emission tomography (PET). Journal of Labelled Compounds and Radiopharmaceuticals, 56 (3-4), 215-224, 2013. DOI: 10.1002/jlcr.3010

  2. Austin, CJD; Kahlert, J; Kassiou, M and Rendina, LM. The translocator protein (TSPO): A novel target for cancer chemotherapy. The International Journal of Biochemistry & Cell Biology, 45 (7), 1212-1216, 2013. DOI: 10.1016/j.biocel.2013.03.004

  3. Boutin, H; Prenant, C; Maroy, R; Galea, J; Greenhalgh, AD; Smigova, A; Cawthorne, C; Julyan, P; Wilkinson, SM; Banister, SD; Brown, G; Herholz, K; Kssiou, M and Rothwell, NJ. [18F]DPA-714: Direct comparison with [11C]PK11195 in a model of cerebral ischemia in rats. PLOS ONE, 8 (2), e56441, 2013. DOI: 10.1371/journal.pone.0056441

  4. Peyronneau, M-A; Saba, W; Goutal, S; Damont, A; Dollé, F; Kassiou, M; Bottlaender, M and Valette, H. Metabolism and quantification of [18F]DPA-714, a new TSPO positron emission tomography radioligand. Drug Metabolism and Disposition, 41 (1), 122-131, 2013. DOI: 10.1124/dmd.112.046342

  5. Wilkinson, SM; Price, J and Kassiou, M. Improved accessibility to the desoxy analogues of Δ9-tetrahydrocannabinol and cannabidiol. Tetrahedron Letters, 54 (1), 52-54, 2013. DOI: 10.1016/j.tetlet.2012.10.080

  6. Corcia, P; Tauber, C; Vercoullie, J; Arlicot, N; Prunier, C; Praline, J; Nicolas, G; Venel, Y; Hommet, C; Baulieu, J-L; cottier, J-P; Roussel, C; Kassiou, M; Guilloteau, D and Ribeiro, M-J. Molecular imaging of microglial activation in amyotrophic lateral sclerosis. PLOS ONE, 7 (12), e52941, 2012. DOI: 10.1371/journal.pone.0052941

  7. Gilmore, AJ; Heblinski, M; Reynolds, A; Kassiou, M and Connor, M. Inhibition of human recombinant T-type calcium channels by N-arachidonoyl 5-HT. British Journal of Pharmacology, 167 (5), 1076-1088, 2012. DOI: 10.1111/j.1476-5381.2012.02047.x

  8. Banister, SD; Manoli, M; Doddareddy, MR; Hibbs, DE and Kassiou, M. A σ1 receptor pharmacophore derived from a series of N-substituted 4-azahexacyclo[5.4.102,6.03,10.05,9.08,11]dodecan-3-ols (AHDs). Bioorganic & Medicinal Chemistry Letters, 22 (19), 6053-6058, 2012. DOI: 10.1016/j.bmcl.2012.08.046

  9. Moussa, IA; Banister, SD; Manoli, M; Doddareddy, MR; Cui, J; Mach, RH and Kassiou, M. Exploration of ring size in a series of cyclic vicinal diamines with σ1 receptor affinity. Bioorganic & Medicinal Chemistry Letters, 22 (17), 5493-5497, 2012. DOI: 10.1016/j.bmcl.2012.07.026

  10. Hicks, C; Jorgensen, W; Brown, C; Fardell, J; Koehbach, J; Grubers, CW; Kassiou, M; Hunt, GE and McGregor, IS. The nonpeptide oxytocin receptor agonist WAY 267,464: Receptor-binding profile, prosocial effects and distribution of c-Fos expression in adolescent rats. Journal of Neuroendocrinology, 24 (7), 1012-129, 2012. DOI: 10.1111/j.1365-2826.2012.02311.x

  11. Gosling, JI; Baker, SP; Haynes, JM; Kassiou, M; Pouton, CW; Warfe, L; White, PJ and Scammells, PJ. Synthesis and biological evaluation of adenosines with heterobicyclic and polycyclic N6-substituents as adenosine A1 receptor agonists. ChemMedChem, 7 (7), 1191-1201, 2012. DOI: 10.1002/cmdc.201200208

  12. Banister, SD; Wilkinson, SM; Hanani, R; Reynolds, AJ; Hibbs, DE and Kassiou, M. A practical, multigram synthesis of the 2-(2-(4-alkoxyphenyl)-5,7-dimethylpy-razolo[1,5-a]pyrimidin-3-yl)acetamide (DPA) class of high affinity translocator protein (TSPO) ligands. Tetrahedron Letters, 53 (29), 3780-3783, 2012. DOI: 10.1016/j.tetlet.2012.05.044

  13. Scarf, AM; Luus, C; da Pozzo, E; Selleri, S; Guarino, C; Martini, C; Ittner, LM and Kassiou, M. Evidence for complex binding profiles and species differences at the translocator protein (TSPO) (18 kDa). Current Molecular Medicine, 12 (4), 488-493, 2012. http://bit.ly/M5l4LM

  14. Scarf, AM; Auman, KM and Kassiou, M. Is there any correlation between binding a functional effects at the translocator protein (TSPO) (18 kDa)? Current Molecular Medicine, 12 (4), 387-397, 2012. http://bit.ly/KN9ZlT

  15. Banister, SD; Rendina, LM and Kassiou, M. 7-azabicyclo[2.2.1]heptane as a scaffold for the development of selective sigma-2 (σ2) receptor ligands. Bioorganic & Medicinal Chemistry Letters, 22 (12), 4059-4063, 2012. DOI: 10.1016/j.bmcl.2012.04.077

  16. Arlicot, N; Vercouillie, J; Ribeiro, M-J; Tauber, C; Venel, Y; Baulieu, J-L; Maia, S; Corcia, P; Stabin, MG; Reynolds, A; Kassiou, M and Guilloteau, D. Initial evaluation in healthy humans of [18F]DPA-714, a potential PET biomarker for neuroinflammation. Nuclear Medicine and Biology, 39 (4), 570-578, 2012. DOI: 10.1016/j.nucmedbio.2011.10.012

  17. Beinat, C; Banister, SD; van Prehn, S; Doddareddy, MR; Hibbs, D; Sako, M; Chebib, M; Tran, T; Al-Muhtasib, N; Xiao, Y and Kassiou, M. Consequences of linker length alteration of the α7 nicotinic acetylcholine receptor (nAChR) agonist, SEN12333. Bioorganic & Medicinal Chemistry Letters, 22 (7), 2380-2384, 2012. DOI: 10.1016/j.bmcl.2012.02.052

  18. Banister, SD and Kassiou, M. The therapeutic potential of sigma (σ) receptors for the treatment of central nervous system diseases: Evaluation of the evidence. Current Pharmaceutical Design, 18 (7), 884-901, 2012. DOI: 10.2174/138161212799436539

  19. Endres, CJ; Coughlin, JM; Gage, KL; Watkins, CC; Kassiou, M and Pomper, MG. Radiation dosimetry and biodistribution of the TSPO ligand 11C-DPA-713 in humans. The Journal of Nuclear Medicine, 53 (2), 330-335, 2012. DOI: 10.2967/jnumed.111.094565

  20. Leaver, KR; Reynolds, A; Bodard, S; Guilloteau, D; Chalon, S and Kassiou, M. Effects of translocator protein (18 kDa) ligands on microglial activation and neuronal death in the quinolinic-acid-injected rat striatum. ACS Chemical Neuroscience, 3 (2), 114-119, 2012. DOI: 10.1021/cn200099e

  21. Issa, F; Kassiou, M and  Rendina, LM.  Boron in drug discovery: carboranes as unique pharmacophores in biologically active compounds.  Chemical Reviews,  111 (9), 5701–5722, 2011. DOI: 10.1021/cr2000866

  22. Crossley, EL; Issa, F; Scarf, AM; Kassiou, M and Rendina, LM. Synthesis and cellular uptake of boron-rich pyrazolopyrimidines: Exploitation of the translocator protein for the efficient delivery of boron into human glioma cells. Chemical Communications, 47 (44), 12179-12181, 2011. DOI: 10.1039/c1cc14587h

  23. Moussa, IA; Banister, SD; Giboureau, N; Meikle, SR and Kassiou, M. Synthesis and in vivo evaluation of [18F]N-(2-benzofuranylmethyl)-N´-[4-(2-fluoroethoxyl)benzyl]piperazine, a novel σ1 receptor PET imaging agent. Bioorganic & Medicinal Chemistry Letters, 21 (22), 6820-6823, 2011. DOI: 10.1016/j.bmcl.2011.09.028

  24. Moussa, IA; Banister, SD; Akladios, FN; Chua, SW and Kassiou, M. Effects of linker elongation in a series of N-(2-benzofuranylmethyl)-N'-(methoxyphenylalkyl)piperazine σ1 receptor ligands. Bioorganic & Medicinal Chemistry Letters, 21 (19), 5707-5710, 2011. DOI: 10.1016/j.bmcl.2011.08.029

  25. Banister, SD; Yoo, DT; Chua, SW; Cui, J; Mach, RH and Kassiou, M. N-arylalkyl-2-azaadamantanes as cage-expanded polycarbocyclic sigma (s) receptor ligands. Bioorganic & Medicinal Chemistry Letters, 21 (18), 5289-5292, 2011. DOI: 10.1016/j.bmcl.2011.07.028

  26. Drake, C; Boutin, H; Jones, MS; Denes, A; McColl, BW; Selvarajah, JR; Hulme, S; Georgiou, RF; Hinz, R; Gerhard, A; Vail, A; Prenant, C; Julyan, P; Maroy, R; Brown, G; Smigova, A; Herholz, K; Kassiou, M; Crossman, D; Francis, S; Proctor, SD; Russell, JC; Hopkins, SJ; Tyrrell, PJ; Rothwell, NJ and Allan, SM. Brain inflammation is induced by co-morbidities and risk factors for stroke. Brain, Behavior, and Immunity, 25 (6), 1113-1122, 2011. DOI: 10.1016/j.bbi.2011.02.008

  27. Boucher, AA; Arnold, JC; Hunt, GE; Spiro, A; Spencer, J; Brown, C; McGregor, IS; Bennett, MR and Kassiou, M. Resilience and reduced c-Fos expression in P2X7 receptor knockout mice exposed to repeated forced swim test. Neuroscience, 189, 170-177, 2011. DOI: 10.1016/j.neuroscience.2011.05.049

  28. Damont, A; Boisgard, R; Kuhnast, B; Lemée, F; Raggiri, G; Scarf, AM; Da Pozzo, E; Selleri, S; Martini, C; Tavitian, B; Kassiou and Dollé, F. Synthesis of 6-[18F]fluoro-PBR28, a novel radiotracer for imaging the TSPO 18 kDa with PET. Bioorganic & Medicianl Chemistry Letters, 21 (16), 4819-4822, 2011. DOI: 10.1016/j.bmcl.2011.06.048

  29. Banister, SD; Moussa, IA; Jorgensen, WT; Chua, SW and Kassiou, M. Molecular hybridization of 4-azahexacyclo[5.4.102,6.03,10.05,9.08,11] dodecane-3-ol with sigma (sigma) receptor ligands modulates off-target activity and subtype selectivity. Bioorganic & Medicinal Chemistry Letters, 21 (12), 3622-3626, 2011. DOI: 10.1016/j.bmcl.2011.04.098

  30. Scarf, AM and Kassiou, M. The translocator protein. Journal of Nuclear Medicine, 52 (5), 677-680, 2011. DOI: 10.2967/jnumed.110.086629

  31. Martin, A; Boisgard, R; Kassiou, M; Dollé, F and Tavitian, B. Reduced PBR/TSPO expression after minocycline treatment in a rat model of focal cerebral ischemia: A PET study using [18F]DPA-714. Molecular Imaging and Biology, 13 (1), 10-15, 2011. DOI: 10.1007/s11307-010-0324-y

  32. Banister, SD; Moussa, IA; Beinat, C; Reynolds, AJ; Schiavini, P; Jorgensen, WT and Kassiou, M. Trishomocubane as a scaffold for the development of selective dopamine transporter (DAT) ligands. Bioorganic & Medicinal Chemistry Letters, 21 (1), 38-41, 2011. DOI: 10.1016/j.bmcl.2010.11.075

  33. Beinat, C; Banister, S; Moussa, I; Reynolds, AJ; McErlean, CSP and Kassiou, M. Insights into structure-activity relationships and CNS therapeutic applications of NR2B selective antagonists. Current Medicinal Chemistry, 17 (34), 4166-4190, 2010. DOI: 10.2174/092986710793348572

  34. Morrison, DE; Issa, F; Bhadbhade, M; Groebler, L; Witting, PK; Kassiou, M; Rutledge, PJ and Rendina, LM. Boronated phosphonium salts containing arylboronic acid, closo-carborane, or nido-carborane: Synthesis, X-ray diffraction, in vitro cytotoxicity, and cellular uptake. J. Biol. Inorg. Chem., 15 (8), 1305-1318, 2010.DOI: 10.1007/s00775-010-0690-6

  35. Banister, S; Roeda, D; Dolle, F and Kassiou, M. Fluorine-18 chemistry for PET: A concise introduction. Current Radiopharmaceuticals, 3 (2), 68-80, 2010.

  36. Giboureau, N; Aumann, KM; Beinat, C and Kassiou, M. Development of vesicular acetylcholine transporter ligands: Molecular probes for Alzheimer's disease. Current Bioactive Compounds, 6 (3), 129-155, 2010. DOI: 10.2174/157340710793237353

  37. Giboureau, N; Som, IM; Boucher-Arnold, A; Guilloteau, D and Kassiou, M. PET radioligands for the vesicular acetylcholine transporter (VAChT). Current Topics in Medicinal Chemistry, 10 (15), 1569-1583, 2010. DOI: 10.2174/156802610793176846

  38. Banister, SD; Clegg, JK; Hanani, R and Kassiou, M. 11-{[2-(3-fluorophenyl)ethyl](methyl)-amino}pentacyclo[5.4.0.02,6.03,10.05,9]-undecan-8-one. Acta Crystallographica Section E, E66 (10), o2693-u1662, 2010. DOI: 10.1107/S1600536810038523

  39. Reynolds, A; Hanani, R; Hibbs, D; Damont, A; Da Pozzo, E; Selleri, S; Dollé, F, Martini, C and Kassiou, M. Pyrazolo[1,5-a]pyrimidine acetamides: 4-Phenyl alkyl ether derivatives as potent ligands for the 18 kDa translocator protein (TSPO). Bioorganic & Medicinal Chemistry Letters, 20 (19), 5799-5802, 2010. DOI: 10.1016/j.bmcl.2010.07.135

  40. Moussa, IA; Banister, SD; Beinat, C; Giboureau, N; Reynolds, AJ and Kassiou, M. Design, synthesis, and structure—affinity relationships of regioisomeric N-benzyl alkyl ether poperazine derivatives as s-1 receptor ligands. J. Med. Chem., 53 (16), 6228-6239, 2010. DOI: 10.1021/jm100639f

  41. Luus, C; Hanani, R; Reynolds, A and Kassiou, M. The development of PET radioligands for imaging the translocator protein (18 kDa): What have we learned? Journal of Labelled Compounds and Radiopharmaceuticals, 53 (7), 501-510, 2010. DOI: 10.1002/jlcr.1752

  42. Gunosewoyo, H and Kassiou, M. P2X purinergic receptor ligands: Recently patented compounds. Expert Opinion on Therapeutic Patents, 20 (5), 625-646, 2010. DOI: 10.1517/13543771003702424

  43. Naidoo-Variawa, S; Lehnert, W; Kassiou, M; Banati, R and Meikle SR. Attenuation correction for the large non-human primate brain imaging using microPET. Phys. Med. Biol., 55 (8), 2351-2363, 2010. DOI: 10.1088/0031-9155/55/8/015

  44. Martín, A; Boisgard, R; Thézé, B; van Camp, N; Kuhnast, B; Damont, A; Kassiou, M; Dollé, F and Tavitian B. Evaluation of the PBR/TSPO radioligand [18F]DPA-714 in a rat model of focal cerebral ischemia. Journal of Cerebral Blood Flow & Metabolism, 30 (1), 230-241, 2010. DOI: 10.1038/jcbfm.2009.205

  45. Banister, SD; Moussa, IA; Jordan, MJT; Coster, MJ and Kassiou, M. Oxo-bridged isomers of aza-trishomocubane sigma (sigma) receptor ligands: Synthesis, in vitro binding and molecular modeling. Bioorganic & Medicinal Chemistry Letters, 20 (1), 145-148, 2010. DOI: 10.1016/j.bmcl.2009.11.019

  46. Edington, AR; McKinzie, AA; Reynolds, AJ; Kassiou, M; Ryan, RM and Vandenberg, RJ. Extracellular loops 2 and 4 of GLYT2 are required for N-arachidonylglycine inhibition of glycine transport. Journal of Biological Chemistry, 284 (52), 36424-36430, 2009. DOI: 10.1074/jbc.M109.017509

  47. Leaver, KR; Allbutt, HN; Creber, NJ; Kassiou, M and Henderson, JM. Oral pre-treatment with epigallocatechin gallate in 6-OHDA lesioned rats produces subtle symptomatic relief but not neuroprotection. Brian Research Bulletin, 80 (6), 397-402, 2009. DOI: 10.1016/j.brainresbull.2009.08.013

  48. Doorduin, J; Klein, HC; Dierckx, RA; James, M; Kassiou, M and de Vries, EFJ. [11C]-DPA-713 and [18F]-DPA-714 as new PET tracers for TSPO: A comparison with [11C]-(R)-PK11195 in a rat model of herpes encephalitis. Mol. Imaging Biol., 11 (6), 386-398, 2009. DOI: 10.1007/s11307-009-0211-6

  49. Reynolds, AJ and Kassiou, M. Recent advances in the Mitsunobu reaction: Modifications and applications to biologically active molecules. Current Organic Chemistry, 13 (16), 1610-1632, 2009. DOI: 10.2174/138527209789578144

  50. Ioppolo, JA; Kassiou, M and Rendina, LM. Water-soluble phosphonium salts containing 1,12-dicarba-closo-dodecaborane(12). Tetrahedron Letters, 50 (47), 6457-6461, 2009. DOI: 10.1016/j.tetlet.2009.08.112

  51. Valette, H; Xiao, Y; Peyronneau, M-A; Damont, A; Kozikowski, AP; Wei, Z-L; Kassiou, M; Kellar, KJ; Dolle, F and Bottlaender, M. 18F-ZW-104: A new radioligand for imagning neuronal nicotinic acetylcholine receptors - in vitro binding properties and PET studies in baboons. The Journal of Nuclear Medicine, 50 (8), 1349-1355, 2009. DOI: 10.2967/jnumed.108.061374

  52. Endres, CJ; Pomper, MG; James, M; Uzuner, O; Hammoud, DA; Watkins, CC; Reynolds, A; Hilton, J; Dannals, RF and Kassiou, M. Initial evaluation of 11C-DPA-713, a novel TSPO PET ligand, in humans. The Journal of Nuclear Medicine, 50 (8), 1276-1282, 2009. DOI: 10.2967/jnumed.109.062265

  53. Dolle, F; Luus, C; Reynolds, A and Kassiou, M. Radiolabelled molecules for imaging the translocator protein (18 kDa) using positron emission tomography. Current Medicinal Chemistry, 16 (22), 2899-2923, 2009. DOI: 10.2174/092986709788803150

  54. Gunosewoyo, H; Coster, MJ; Bennett, MR and Kassiou, M. Purinergic P2X(7) receptor antagonists: Chemistry and fundamentals of biological screening. Bioorganic & Medicinal Chemistry, 17 (14), 4861-4865, 2009. DOI: 10.1016/j.bmc.2009.05.083

  55. Chauveau, F; Van Camp, N; Dolle, F; Kuhnast, B; Hinnen, F; Damont, A; Boutin, H; James, M; Kassiou, M and Tavitian, B. Comparative evaluation of the translocator protein radioligands C-11-DPA-713, F-18-DPA-714, and C-11-PK11195 in a rat model of acute neuroinflammation. Journal of Nuclear Medicine, 50 (3), 468-476, 2009. DOI: 10.2967/jnumed.108.058669

  56. Warraich, ST; Allbutt, HN; Billing, R; Radford, J; Coster, MJ; Kassiou, M and Henderson, JM. Evaluation of behavioural effects of a selective NMDA NR1A/2B receptor antagonist in the unilateral 6-OHDAlesion rat model. Brain Research Bulletin, 78 (2-3), (Special Issue), 85-90, 2009. DOI: 10.1016/j.brainresbull.2008.08.023

  57. Truong, L; Allbutt, HN; Coster, MJ; Kassiou, M and Henderson, JM. Behavioural effects of a selective NMDA NR1A/2B receptor antagonist in rats with unilateral 6-OHDA + parafascicular lesions. Brain Research Bulletin, 78 (2-3), (Special Issue), 91-96, 2009. DOI: 10.1016/j.brainresbull.2008.10.004

  58. Kassiou, M; Banati, R; Holsinger, RMD and Meikle, S. Challenges in molecular imaging of Parkinson's disease: A brief overview. Brain Research Bulletin, 78 (2-3), (Special Issue), 105-108, 2009. DOI: 10.1016/j.brainresbull.2008.08.006

  59. Scarf, AM; Ittner, LM and Kassiou, M. The translocator protein (18 kDa): Central nervous system disease and drug design. Journal of Medicinal Chemistry, 52 (3), 581-592, 2009. DOI: 10.1021/jm8011678