Gianfranco Balboni

 
balboni_gianfranco

Gianfranco Balboni
Address: Department of Life and Environment Sciences
Via Ospedale 72
Cagliari
Phone: +39 070 675 8632
Fax: —
Email: gbalboni@unica.it

Curriculum vitae

1980: Degree in Medicinal Chemistry and Technology “Cum Laude”, University of Ferrara
1981: Degree in Pharmacy “Cum Laude”, University of Ferrara.
1986: PhD in Pharmaceutical Sciences.
1986: Organic Chemistry Researcher.
1989-1998: Medicinal Chemistry Researcher.
1990: Specialization in Cosmetic Science and Technology.
1998- : Associate Professor in Medicinal Chemistry (CHIM/08): Course of Medicinal and Toxicologycal Chemistry (10 CFU) for Degree in Pharmacy; and Course of Toxicologycal Chemistry (7 CFU) for Degree in Toxicology.

Lines of research

  1. Synthesis and structure / activity relationship studies of opioid peptides and pseudopeptides derived from the Dmt-Tic pharmacophore (2′,6′-dimethyl-L-tyrosine – 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid).
    The discovery by us of this pharmacophore has resulted in a significant number of derivatives that are still the subject of numerous prestigious international collaborations. Among the most important compounds obtained in this area are definitely worth remembering: UFP-512: H-Dmt-Tic-Asp-Bid (Bid = 1H-benzimidazole-2-yl) (delta selective agonist) the subject of numerous studies on the antidepressant effect, interaction with mu / delta heterodimeric receptors, and electrophysiology of ion fluxes in the ischemic cerebral cortex; UFP-505: H-Dmt-Tic-Gly-NH-Bzl (mu agonist / delta antagonist) and MD-1: H-Dmt-Tic-Gly-NH-Ph (mu agonist / delta agonist) are currently being evaluated for their analgesic activity without induction of tolerance and dependence; MZ-2: H-Dmt-Tic-Lys-NH-Bzl (mu antagonist / delta antagonist), peptide able to fight osteoporosis and obesity.
  2. Non-peptide prokineticin receptor antagonists.
    Starting from some patents filed recently, with my group research have developed a new method of synthesis that allows easy access to these interesting derivatives. From an initial screening of about 50 compounds, we identified a some selective antagonists for the PKR-1 receptor. These new products have generated considerable interest in the national and international scientific communities and are currently the subject of numerous pharmacological studies in various fields which include: inflammatory pain, interaction with TRPV-1 receptor, multiple sclerosis, reproductive disorders, cerebral ischemia and hypopituitarism. Our research group has also developed the first prokineticin receptor antagonist containing 18F useful for PET imaging.
  3. Flavonoids.
    Since last year our research group is also involved in synthesis and development of flavonoids endowed with a broad-spectrum of activities. Indeed, considering that generally flavonoids show the same activities of resveratrol, we have established a series of collaborations with various national and international laboratories for the study of these compounds. Until now we showed that our derivatives are able of to bind aryl hydrocarbon receptors receptors manifesting a series of different effects: agonist, partial agonist and antagonist according to the different substituents. In addition, we have also highlighted their activity as carbonic anhydrase inhibitors. Currently, this class of compounds are ongoing studies on: the antioxidant effect (some of them showed values 3 times higher than those of Trolox used as a reference), mitochondrial biogenesis, modulation of SIRT1 activity, and the ability to chelate metals associated with the beta-amyloid.
  4. Photocytotoxic diaryl-pyridines.
    Lately, after stressing the antiproliferative activity of some diaryl-pyridines, in view of their structure, we have identified the possibility of obtaining new compounds with photocytotoxic properties after introduction of fluorescent groups. In preliminary studies they showed photocytotoxic activity at submicromolar dosage in different cell lines.

Publications from 2008 to 2015

  1. CONGIU C, ONNIS V, BALBONI G, SCHIANO-MORIELLO A, DI MARZO V, DE PETROCELLIS L. (2015) TRPV1 modulators: Synthesis and in vitro evaluation of 1-heteroarylpiperidinecarboxamide and piperazinylurea derivatives. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, vol.100, p. 129-138.
  2. ABOU-HAMDAN M, COSTANZA M, FONTANA E, DI DARIO M, MUSIO S, CONGIU C, ONNIS V, LATTANZI R, RADAELLI M, MARTINELLI V, SALVADORI S, NEGRI L, POLIANI PL, FARINA C, BALBONI G, STEINMAN L, PEDOTTI R. (2015) Critical role for prokineticin 2 in CNS autoimmunity. NEUROLOGY® NEUROIMMUNOLOGY & NEUROINFLAMMATION, vol. 2, p. e95.
  3. CAO S; CHAO D; ZHOU H; BALBONI G; XIA Y. (2015) A novel mechanism for cytoprotection against hypoxic injury: delta-opioid receptor-mediated increase in Nrf2 translocation. BR. J. PHARMACOL.vol. 172, p. 1869-1881.
  4. LATTANZI R; MAFTEI D; MARCONI V; FLORENZANO F; FRANCHI S; BORSANI E; RODELLA LF; BALBONI G; SALVADORI S; SACERDOTE P; NEGRI L. (2015) Prokineticin 2 upregulation in the peripheral nervous system has a major role in triggering and maintaining neuropathic pain in the chronic constriction injury model. BIOMED RESEARCH INTERNATIONAL, vol. 2015, article ID 301292.
  5. GUIDA F; LATTANZI R; BOCCELLA S; MAFTEI D; ROMANO R; MARCONI V; BALBONI G; SALVADORI S; SCAFURO MA; DE NOVELLIS V; NEGRI L; MAIONE S; LUONGO L. (2015) PC1, a non-peptide PKR1-preferring antagonist, reduces pain behavior and spinal neuronal sensitization in neuropathic mice. PHARMACOLOGICAL RESEARCH, vol. 91, p. 36-46.
  6. LIANG J; CHAO D; SANDHU HK; YU Y; ZHANG L; BALBONI G; KIM DH; XIA Y. (2014) Delta-opioid receptors up-regulate excitatory amino acid transporter in mouse astrocytes. BRITISH JOURNAL PHARMACOLOGY, vol. 171, p. 5417-5430.
  7. LATTANZI R; CONGIU C; ONNIS V; DEPLANO A; SALVADORI S; MARCONI V; MAFTEI D; FRANCIOSO A; AMBROSIO C; CASELLA I; COSTA T; CALTABIANO G; MATSOUKAS MT; BALBONI G; NEGRI L. (2014) Halogenated trizinediones behave as antagonists of PKR1: in-vitro and in-vivo pharmacological characterization. INTERNATIONAL JOURNAL OF PHARMACEUTICAL SCIENCES AND RESEARCH, vol. 5, p. 5064-5072.
  8. DE TOMA AS; KRISHNAMOORTHY J; NAM Y; JIN LEE H; BRENDER JR; KOCHI A; LEE D; ONNIS V; CONGIU C; MANFREDINI S; VERTUANI S; BALBONI G; RAMAMOORTHY A; LIM MH. (2014) interaction and reactivity of synthetic aminoisoflavones with metal-free and metal-associated amyloid-beta. CHEMICAL SCIENCE, vol. 5 p. 4851-4862.
  9. MAFTEI D; MANCONI V; FLORENZANO F; GIANCOTTI LA; CASTELLI M; MORETTI S; BORSANI E; RODELLA LF; BALBONI G; LUONGO L; MAIONE S; SACERDOTE P; NEGRI L; LATTANZI R. (2014) Controlling the activation of the Bv8/prokineticin system reduces neuroinflammation and abolishes thermal and tactile hyperalgesia in neuropathic animals. BRITISH JOURNAL OF PHARMACOLOGY, vol. 171, p. 4850-4865.
  10. KABLI N; NGUYEN T; BALBONI G; O’DOWD BF; GEORGE SR. (2014) Antidepressant-like and anxiolytic-like effects following activation of the mu-delta opioid receptor heteromer in the nucleus accumbens. MOLECULAR PSYCHIATRY, vol. 19, p, 986-994.
  11. CONGIU C; ONNIS V; DEPLANO A; SALVADORI S; MARCONI V; MAFTEI D; NEGRI L; LATTANZI R; BALBONI G. (2014) A new convenient synthetic method and preliminary pharmacological characterization of triazinediones as prokineticin receptor antagonists. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, vol. 81, p. 334-340.
  12. CONGIU C; ONNIS V; BALBONI G; SUPURAN CT (2014) Synthesis and carbonic anhydrase I, II, IX and XII inhibition studies of 4-N,N-disubstituted sulanilamides incorporating 4,4,4-trifluoro-3-oxo-but-1-enyl, phenacylthiourea and imidazol-2(3H)-one/thione moieties. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 24, p. 1776-1779.
  13. CHARFI I; NAGI K; MNIE-FILALI O; THIBAULT D; BALBONI G; SCHILLER PW; TRUDEAU LE; PINEYRO G. Ligand- and cell-dependent determinants of internalization and cAMP modulation by delta opioid receptor (DOR) agonists. (2014) CELLULAR AND MOLECULAR LIFE SCIENCES, vol. 71, p. 1529-1546.
  14. TIAN X, HUA F, SANDHU H K, CHAO D, BALBONI G, SALVADORI S, HE X, XIA Y (2013). Effect of delta-opioid receptor activation on BDNF-TrkB vs. TNF-Alpha in the mouse cortex exposed to prolonged hypoxia. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, vol. 14, p. 15959-15976.
  15. LESMA G, SALVADORI S, AIRAGHI F, MURRAY TF, RECCA T, SACCHETTI A, BALBONI G, SILVANI A. (2013). Structural and biological exploration of Phe3-Phe4-modified endomorphin-2 peptidomimetics.. ACS MEDICINAL CHEMISTRY LETTERS, vol. 4, p. 795-799
  16. VEZZI V, ONARAN HO, MOLINARI P, GUERRINI R, BALBONI G, CALO’ G, COSTA T. (2013). Ligands raise the constraint that limits constitutive activation in G protein-coupled opioid receptors.. JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 288, p. 23964-23978
  17. HE X, YANG Y, ZHI F, MOORE ML, KANG X, CHAO D, WANG R, BALBONI G, SALVADORI S, KIM DH, XIA Y. (2013) Delta-opioid receptor activation modified microRNA expression in the rat kidney under prolonged hypoxia. PLOS ONE, vol. 8, e61080.
  18. LESMA G, SALVADORI S, AIRAGHI F, BOJNIK E, BORSODI A, RECCA T, SACCHETTI A, BALBONI G, SILVANI A. (2013) Synthesis, pharmacological evaluation and conformational investigation of endomorphin-2 hybrid analogues. MOLECULAR DIVERSITY, vol. 17, p. 19-31.
  19. RICHARD-LALONDE M, NAGI K, AUDET N, SLENO R, AMRAEI M, HOGUE M, BALBONI G, SCHILLER P W, BOUVIER M, HÉBERT T E, PINEYRO G. (2013) Conformational dynamics of KIR3.1/KIR3.2 channel activation via delta-opioid receptors. MOLECULAR PHARMACOLOGY, vol. 83, p. 416-428.
  20. CHAO D, HE X, YANG Y, BALBONI G, SALVADORI S, KIM DH, XIA Y. (2012) Hydrogen sulfide induced disruption of Na+ homeostasis in the cortex. TOXICOLOGICAL SCIENCES, vol. 128, p. 198-208.
  21. CHAO D, HE X, YANG Y, BAZZY-ASAAD A, LAZARUS LH, BALBONI G, KIM DH, XIA Y. (2012) DOR activation inhibits anoxic/ischemic Na+ influx through Na+ channels via PKC mechanisms in the cortex. EXPERIMENTAL NEUROLOGY. vol 236; p. 228-239.
  22. WALL R J, HE G, DENISON M S, CONGIU C, ONNIS V, FERNANDES A, BELL D R, ROSE M, CRAIG ROWLANDS J, BALBONI G, MELLOR I R. (2012) Novel 2-amino-isoflavones exhibit aryl hydrocarbon receptor agonist or antagonist activity in a species/cell-specific context. TOXICOLOGY. vol. 297; p. 26-33.
  23. BALBONI G, CONGIU C, ONNIS V, MARESCA A, SCOZZAFAVA A, WINUM J-Y, MAIETTI A, SUPURAN CT. (2012) Flavones and structurally related 4-chromenones inhibit carbonic anhydrases by a different mechanism of action compared to coumarins.
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. vol. 22; p. 3063-3066.
  24. JACOBSON O, WEISS ID, NIU G, BALBONI G, CONGIU C, ONNIS V, KIESEWETTER DO, LATTANZI R, SALVADORI S, CHEN X. (2011) Prokineticin receptor 1 antagonist PC-10 as a biomarker for imaging inflammatory pain. THE JOURNAL OF NUCLEAR MEDICINE. vol. 52; p. 600-607.
  25. BALBONI G, SALVADORI S, MARCZAK E. D, KNAPP J. M, LAZARUS L. H, PENG X, SI Y. G, NEUMEYER J. L. (2011) Opioid bifunctional ligands from morphine and the opioid pharmacophore Dmt-Tic. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. vol. 46; p. 799-803.
  26. KABLI N, MARTIN N, FAN T, NGUYEN T, HASBI A, BALBONI G, O’DOWD BF, GEORGE SR. (2010) Agonists at the delta-opioid receptor modify the binding of mu-receptor agonists to the mu-delta receptor hetero-oligomer. BRITISH JOURNAL OF PHARMACOLOGY. vol. 161; p. 1122-1136.
  27. BALBONI G, MARZOLA E, SASAKI Y, AMBO A, MARCZAK E. D, LAZARUS L. H, SALVADORI S. (2010) Role of 2′,6′-dimethyl-L-tyrosine (Dmt) in some opioid lead compounds. BIOORGANIC & MEDICINAL CHEMISTRY, vol. 18; p. 6024-6030.
  28. BALLET S, MARCZAK E D, FEYTENS D, SALVADORI S, SASAKI Y, ABELL A. D, LAZARUS L. H, BALBONI G., TOURWE’ D. (2010) Novel multiple opioid ligands based on 4-aminobenzazepinone (Aba), azepinoindole (Aia) and tetrahydroisoquinoline (Tic) scaffolds. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 20; p. 1610-1613.
  29. BALBONI G., SALVADORI S., TRAPELLA C., KNAPP B. I., BIDLACK J. M., LAZARUS L. H., PENG X., NEUMEYER J. L. (2010) Evolution of the bifunctional lead mu agonist / delta antagonist containing the 2′,6′-dimethyl-L-tyrosine-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Dmt-Tic) opioid pharmacophore. ACS CHEMICAL NEUROSCIENCE, vol. 1; p. 155-164.
  30. KANG X, CHAO D, GU Q, DING G, WANG Y, BALBONI G., LAZARUS L. H, XIA Y (2009). Delta-opioid receptors protect from anoxic disruption of Na+ homeostasis via Na+ channel regulation. CELLULAR AND MOLECULAR LIFE SCIENCES, vol. 66; p. 3505-3516.
  31. BALBONI G., TRAPELLA C, SASAKI Y, AMBO A, MARCZAK E. D, LAZARUS L. H, SALVADORI S . (2009) Influence of the side chain next to C-terminal benzimidazole in opioid pseudopeptides containing the Dmt-Tic pharmacophore. JOURNAL OF MEDICINAL CHEMISTRY, vol. 52; pp. 5556-5559.
  32. GIANNINI E, LATTANZI R, NICOTRA A, CAMPESE A. F, GRAZIOLI P, SCREPANTI I, BALBONI G., SALVADORI S, SACERDOTE P, NEGRI L. (2009) The chemokine Bv8/prokineticin 2 is up-regulated in inflammatory granulocytes and modulates inflammatory pain. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA vol. 106; pp. 14646-14651.
  33. MARCZAK E.D., JINSMAA Y., MYERS P.H., BLANKENSHIP T., WILSON R., BALBONI G., SALVADORI S., LAZARUS L. H. (2009) Orally administered H-Dmt-Tic-Lys-NH-CH2-Ph (MZ-2), a potent mu/delta-opioid receptor antagonist, regulates obese-related factors in mice. EUR. J. PHARMACOL. vol. 616, pp. 115-121.
  34. CHAO D, BALBONI G., LAZARUS L. H, SALVADORI S, XIA Y. (2009). Na+ mechanism of delta-opioid receptor induced protection from K+ leakage in the cortex. CELLULAR AND MOLECULAR LIFE SCIENCES. vol. 66, pp. 1105-1115.
  35. KANG XUE-ZHI, GU QUAN-BAO, DING GUANG-HONG, CHAO DONG-MAN, WANG YING-WEI, BALBONI G., LAZARUS L. H, XIA YING. (2008). Delta-opioid receptor induced inhibition of sodium channel function. JOURNAL OF ACUPUNCTURE AND TUINA SCIENCE. vol. 6, pp. 276-278.
  36. BALLET S, FEYTENS D, DE WACHTER R, DE VLAEMINCK M, MARCZAK E. D, SALVADORI S, DE GRAAF C, ROGNAN D, NEGRI L, LATTANZI R, LAZARUS L. H, TOURWE’ D, BALBONI G. (2009). Conformationally constrained opioid ligands: the Dmt-Aba and Dmt-Aia versus Dmt-Tic scaffold. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. vol. 19, pp. 433-437 .
  37. BALBONI G., LAZZARI I, TRAPELLA C, NEGRI L, LATTANZI R, GIANNINI E, NICOTRA A, MELCHIORRI P, VISENTIN S, DE NUCCIO C, SALVADORI S. (2008). Triazine compounds as antagonists at Bv8-prokineticin receptors. JOURNAL OF MEDICINAL CHEMISTRY. vol. 51, pp. 7635-7639 .
  38. JINSMAA Y, MARCZAK E. D, BALBONI G., SALVADORI S, LAZARUS L. H. (2008). Inhibition of the development of morphine tolerance by a potent dual mu- / delta-opioid antagonist, H-Dmt-Tic-Lys-NH-CH2-Ph. PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR. vol. 90, pp. 651-657 .
  39. CHAO D, BAZZY-ASAAD A, BALBONI G., SALVADORI S, XIA Y. (2008). Activation of DOR attenuates anoxic K+ derangement via inhibition of Na+ entry in mouse cortex. CEREBRAL CORTEX (on line). vol. 18, pp. 2217-2227.
  40. BALBONI G., FIORINI S, BALDISSEROTTO A, TRAPELLA C, SASAKI Y, AMBO A, MARCZAK E. D, LAZARUS L. H, SALVADORI S. (2008). Further studies on lead compounds containing the opioid pharmacophore Dmt-Tic. JOURNAL OF MEDICINAL CHEMISTRY. vol. 51, pp. 5109-5117.
  41. SALVADORI S, FIORINI S, TRAPELLA C, PORRECA F, DAVIS P, SASAKI Y, AMBO A, MARCZAK E D, LAZARUS L H, BALBONI G. (2008) Role of benzimidazole (Bid) in the delta-opioid agonist pseudopeptide H-Dmt-Tic-NH-CH2-Bid (UFP-502). BIOORGANIC & MEDICINAL CHEMISTRY vol. 16, pp. 3032-3038.
  42. RYU E K, WU Z, CHEN K, LAZARUS L H, MARCZAK E D, SASAKI Y, AMBO A, SALVADORI S, REN C, ZHAO H, BALBONI G, CHEN X. (2008) Synthesis of a potent and selective (18)F-labeled delta-opioid receptor antagonist derived from the Dmt-Tic pharmacophore for positron emission tomography imaging. JOURNAL OF MEDICINAL CHEMISTRY vol. 51, pp. 1817-1823.
  43. VERGURA R, BALBONI G, SPAGNOLO B, GAVIOLI E, LAMBERT D. G, MADONALD J, TRAPELLA C, LAZARUS L. H, REGOLI D, GUERRINI R, SALVADORI S, CALO’ G. (2008) Anxiolytic- and antidepressant-like activities of H-Dmt-Tic-NH-CH(CH2-COOH)-Bid (UFP-512), a novel selective delta opioid receptor agonist. PEPTIDES vol. 29, pp. 93-103.

Active collaborations with other research groups

Prof. Ying Xia Department of Neurosurgery; University of Texas Medical School at Houston (USA).
Prof. Neumeyer L. John, McLean Hospital, Harward Medical School (USA).
Prof. Mi Hee Lim, Life Science Institute, University of Michigan (USA).
Prof. George R. Susan, Department of Pharmacology; University of Toronto (CANADA).
Prof. Graciela Pineyro, Department of Psychiatry and Pharmacology, University of Montreal (CANADA).

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