SinFarm (CHIM/08)

Attività di ricerca

Our research focuses on developing anti-mycobacterial agents and antibody drug conjugates (ADCs) for immunomodulation.
With the emergence of resistant M. tuberculosisstrains (MDR and XDR), co-infection with HIV, the existence of latent tuberculosis infectious (LTBI) and the extensive treatment regimen, our medicinal chemistry program aims at identifying new anti-TB drugs that target both MDR and XDR strains, that are compatible with ART and kill M. tuberculosisin its different physiological states, including LTBI. In this context, we are developing two classes of anti-mycobacterial compounds: MmpL3 inhibitors and compounds that inhibit tryptophan biosynthesis.
The rapid and robust transcriptional induction of the ELR+CXC class of chemokines is necessary to induce neutrophil chemotaxis, the first line of the mammalian innate immune defense. Many critical proinflammatory genes, such as the chemokines, exhibit accessible promoters and are therefore primed for rapid activation. The promoters of these genes are enriched for histone H3K4 trimethylation (H3K4me3), an active chromatin mark that is catalyzed by the mixed-lineage leukemia (MLL) family of methyltransferases. MLL1 is one of the six MLL histone methyltransferases (HMTs) in mammals. In this context, we are developing a new class of ADCs to deliver compounds that can block MLL1 activity.
 

Collaborazioni nazionali e internazionali
  • Eric J. Rubin (Harvard T.H. Chan School of Public Health, USA)
  • Lluis Ballell (Diseases of the Developing World, Tres Cantos Medicines Development Campus, GSK, Spain)
  • Musa Mhlanga (University of Cape Town, South Africa)
  • Kelly Chibale (University of Cape Town, South Africa)
  • Shu-Sin Chng (National University of Singapore, Singapore)
  • Maurizio Anzini (Università di Siena, Italy)
  • Lidia Sautebin (Università degli Studi di Napoli Federico II, Italy)
  • Carla Ghelardini (Università degli Studi di Firenze, Italy)
  • Paola Patrignani (Università degli Studi di Chieti G. d’Annunzio, Italy)
  • Alessandro De Logu (Università degli Studi di Cagliari, Italy)
  • Giulio Vistoli (Università degli Studi di Milano, Italy)
  • Lanfranco Fattorini (Istituto Superiore di Sanità, Italy).
Strumentazione

lab fully equipped for organic synthesis, access to NMR departmental facilities

Settori ERC

LS7_3 - Pharmacology, pharmacogenomics, drug discovery and design, drug therapy

Finanziamenti
  • 2015- Progetti di Ricerca Universitari: “Targeting tryptophan biosynthesis to treat tuberculosis”
  • 2016- Grandi Ricerche Universitarie: "Novel MmpL3 inhibitors to treat tuberculosis”
  • 2017- Grandi Ricerche Universitarie: “Novel MmpL3 inhibitors-loaded niosomes to treat tuberculosis via lung delivery”
     
Pubblicazioni
Pubblicazioni ultimi 10 anni
  1. Poce G, Consalvi S, Venditti G, Alfonso S, Desideri N, Fernandez-Menendez R,  Bates RH,  Ballell L, Barros Aguirre D, Rullas J, De Logu A, Gardner M, Ioerger T, Rubin EJ, Biava M Novel Pyrazole-Containing Compounds Active against Mycobacterium tuberculosis, ACS Med Chem Letters, 10, 1423-1429, 2019
  2. Raguzzini A, Poce G, Consalvi S, Toti E, Palmacci F, Biava M, Peluso I,  Chocolate consumers and lymphocyte-to-monocyte ratio: A working hypothesis from a preliminary report of a pilot study in celiac subjects, Antioxidant, 10, 440, 2019
  3. Consalvi S, Scarpecci C, Biava M, Poce G Mycobacterial tryptophan biosynthesis: A promising target for tuberculosis drug development? Bioorg Med Chem lett, 2019
  4. Aiello P, Consalvi S, Poce G, Raguzzini A, Toti E, Palmery M, Biava M, Bernardi M, Kamal MA, Perry G, Peluso I Dietary flavonoids: Nano delivery and nanoparticles for cancer therapy, Semin Cancer Biol, 2019
  5. Palmacci F, Toti E, Raguzzini A, Catasta G, Aiello P, Peluso I, Biava M, Palmery M Neutrophil-to-Lymphocyte Ratio, Mediterranean Diet, and Bone Health in Coeliac Disease Patients: A Pilot Study, Oxid Med Cell Longev, 14 pages, 2019
  6. Biava M Introduction to COX inhibitors, Future Medicinal Chemistry, 10, 1737-1740, 2018.
  7. Cheleschi S, Calamia V, Fernandez-Moreno M, Biava M, Giordani A, Fioravanti A, Anzini M, Blanco F In vitro comprehensive analysis of VA692 a new chemical entity for the treatment of osteoarthritis, International Immunopharmacology, 64, 86-100, 2018. 
  8. Poce G, Cocozza M, Alfonso S, Consalvi S, Venditti G, Fernandez-Menendez R, Bates RH, Barros Aguirre D, Ballell L, De Logu A, Vistoli G, Biava M In vivo potent BM635 analogue with improved drug-like properties, European J Med Chem, 145, 539-550, 2018.
  9. Venditti G, Poce G, Consalvi S, Biava M 1,5-Diarylpyrroles as potent antitubercular and anti-inflammatory agents, Chemistry of Heterocyclic Compounds, 1-11, 2017
  10. Poce G, Consalvi S, Cocozza M, Fernandez-Menendez R, Bates RH, Ortega Muro F, Barros Aguirre D, Ballell L, Biava M Pharmaceutical salt of BM635 with improved bioavailability, European Journal of Pharmaceutical Sciences 99, 17-23, 2017
  11. Consalvi S, Biava M, Poce G A series of COX-2 inhibitors endowed with NO-releasing properties: synthesis, biological evaluation and docking analysis. ChemMedChem  11, 1804-1811, 2016
  12. Di Capua A, Sticozzi C, Brogi S, Brindisi M,  Cappelli A,  Sautebin L,  Rossi A,  Pace S,  Ghelardini C,  Di Cesare Mannelli L,  Valacchi G,  Giorgi G,  Giordani A,  Poce G,  Biava M,  Anzini, M  Synthesis and biological evaluation of fluorinated 1,5-diarylpyrrole-3-alkoxyethyl ether derivatives as selective COX-2 inhibitors endowed with anti-inflammatory activity. European J Med Chem, 109, 99-106, 2016.
  13. Desideri N, Proietti Monaco L, Fioravanti R, Biava M, Yáñez M, Alcaro S, Ortuso F (E)-3-Heteroarylidenechroman-4-ones as potent and selective monoamine oxidase-B inhibitors. European J Med Chem, 117, 292–300, 2016
  14. Poce G, Consalvi S, Biava M MmpL3 inhibitors: diverse chemical scaffolds inhibit the same target.      Mini Rev Med Chem. 16, 1274-1283, 2016
  15. Consalvi S, Biava M, Poce G COX inhibitors: a patent review (2011 - 2014). Expert Opin Ther Pat 25, 1357-71, 2015Poce G, Biava M Overcoming drug resistance for tuberculosis. Future Microbiology 10, 1735–1741, 2015
  16. Poce G, Biava M Overcoming drug resistance for tuberculosis. Future Microbiology 10,1735-1741, 2015
  17. Fioravanti R, Desideri N, Biava M, Droghini P, Atzori EM, Ibba C, Collu G, Sanna G, Delogu I, Loddo R, N-((1,3-Diphenyl-1H-pyrazol-4-yl)methyl)anilines: A novel class of anti-RSV agents. Bioorg Med Chem Lett.  25, 2401-2404, 2015
  18. Cheleschi S, Pascarelli NA, Valacchi G, Di Capua A, Biava M, Belmonte G, Giordani A, Sticozzi C, Anzini M, Fioravanti A Chondroprotective effect of three different classes of anti-inflammatory agents on human osteoarthritic chondrocytes exposed to IL-1β.Int Immunopharmacol, 28, 794-801, 2015
  19. Piccaro G, Poce G, Biava M, Giannoni F, Fattorini L Activity of lipophilic and hydrophilic drugs against dormant and replicating Mycobacterium tuberculosis. Journal of Antibiotics, 68, 711-714, 2015
  20. Dragset Marte S, PoceG, Alfonso S, Padilla-Benavides T, Ioerger T R, Kaneko T, Sacchettini JC, Biava M, Parish T, Argüello JM, Steigedal M, Rubin EJ, A Novel Antimycobacterial Compound Acts as an Intracellular Iron Chelator. AAC, 59, 2256-64, 2015.
  21. Consalvi S, Alfonso S, Di Capua A, Poce G, Pirolli A, Sabatino M, Ragno R, Anzini M, Sartini S, La Motta C, Ghelardini C, Di Cesare Mannelli L, Ghelardini C,  Biava M Synthesis, biological evaluation and docking analysis of a new series of methylsulfonyl and sulfamoyl acetamides and ethyl acetates as potent COX-2 inhibitors. Bioorg Med Chem, 23, 810–820, 2015.
  22. Poce G, Cocozza M, Consalvi S, Biava M SAR analysis of new anti-TB drugs currently in pre-clinical and clinical development. Eur J Med Chem, 86, 335-351, 2014.
  23. Biava M, Battilocchio C, Poce G, Alfonso S, Porretta GC, Consalvi S, Calderone V, Martelli A, Testai L, Sautebin L, Rossi A, Ghelardini C, Di Cesare Mannelli L, Giordani A, Patrignani P, Anzini M Enhancing the pharmacodynamic profile of a class of selective COX-2 inhibiting nitric oxide donors. Bioorg Med Chem, 22,  772–786, 2014
  24. Martelli A, Testai L, Anzini M, Cappelli A, Di Capua A, Biava M, Poce G, Consalvi S, Giordani A, Caselli G, Rovati L, Ghelardini C, Patrignani P, Sautebin L, Breschi MC, Calderone V The novel anti‐Inflammatory agent VA694, endowed with both NO‐Releasing and COX2‐selective inhibiting properties, exhibits NO‐mediated positive effects on blood pressure, coronary flow and endothelium in an experimental model of hypertension and endothelial dysfunction. Pharmacol Research, 78, 1– 9, 2013.
  25. Radi M, Bernardo V, Vignaroli G, Brai A, Biava M, Schenone S, Botta M An alternative synthetic approach for the synthesis of biologically relevant 1,4-disubstituted pyrazolo[3,4-d]pyrimidines. Tetrahedron Lett, 54, 5204-5206, 2013.
  26. Fioravanti R, Desideri N, Biava M, Proietti Monaco L, Grammatica L, Yàñez M Design, synthesis, and in vitro hMAO-B inhibitory evaluation of some 1-methyl-3,5-diphenyl-4,5-dihydro-1H-pyrazoles. Bioorg Med Chem Lett, 23, 5128-5130, 2013.
  27. Tintori C,  Laurenzana I, La Rocca F,  Falchi F, Carraro F, Ruiz A, Esté JA, Kissova M, Crespan E, Maga G, Biava M, Brullo C, Schenone S, Botta M Identification of Hck inhibitors as hits for the development of antileukemia and anti-HIV agents. ChemMedChem, 8, 1353-1360, 2013.
  28. Battilocchio C, Guetzoyan L, Cervetto C,  Di Cesare Mannelli L, Frattaroli D, Baxendale IR, Maura G, Rossi A, Sautebin L, Biava M, Ghelardini C, Marcoli M, Ley SV Flow synthesis and bio-pharmacological studies of an adamantane derivative that shows analgesic activity and inhibits the P2X7-evoked glutamate release. ACS Med Chem Lett, 4, 704-709, 2013.
  29. Friggeri L, Ballante F, Ragno R, Musmuca I, De Vita D, Manetti F, Biava M, Scipione L, Di Santo R, Costi R, Feroci M, Tortorella S Pharmacophore assessment through 3-D QSAR: evaluation of the predictive ability on new derivatives by the application on a serie of antitubercular agents. J Chem Inf Model, 53, 1463-1474, 2013.
  30. Mazzarino M,  Biava M, de la Torre X, Fiacco I, Botrè F  Characterization of the biotransformation pathways of clomiphene, tamoxifen and toremifene as assessed by LC-MS/(MS) following in vitro and excretion studies. Anal Bioanal Chem, 405, 5467-5487, 2013.
  31. Baiocco P, Poce G, Alfonso S, Cocozza M, Porretta GC, Colotti G, Biava M, Moraca F, Botta M, Yardley V, Fiorillo A, Malatesta F,  Ilari A Evaluation of azole-based compounds as inhibitors of trypanothione reductase from leishmania infantum: a comparative analysis with its physiological substrate by X-ray crystallography. ChemMedChem, 8, 1175-1183, 2013.
  32. Battilocchio C, Poce G, Alfonso S, Porretta GC, Consalvi S, Sautebin L, Rossi A, Pace F, Ghelardini C, Di Cesare Mannelli L, Schenone S, Giordani A, Di Francesco L, Patrignani P,  Biava M  A class of pyrrole derivatives endowed with analgesic/anti-inflammatory activity. Bioorg Med Chem, 21, 3695-3701, 2013.
  33. Anzini M, Di Capua A, Valenti S, Brogi S, Rovini M, Giuliani G, Cappelli A, Vomero S, Chiasserini L, Saga A, Poce G, Giorgi G, Calderone V, Martelli A, Testai L, Sautebin L, Rossi A, Papa G, Ghelardini C, Di Cesare Mannelli L, Benetti V, Giordani A, Anzellotti P, Dovizio M, Patrignani P, Biava M  Novel analgesic/anti-inflammatory agents: 1,5-diarylpyrrole nitro-oxyalkyl ethers and related compounds as cyclooxygenase-2 inhibiting nitric oxide donors.  J Med Chem, 56, 3191-3206, 2013.
  34. Sticozzi C, Belmonte G, Cervellati F, Di Capua A, Maioli E, Cappelli A, Giordani A, Biava M, Anzini M, Valacchi G Antiproliferative effect of two novel COX-2 inhibitors on human keratinocytes. Eur J Pharm Sci,  49, 133-141, 2013.
  35. Poce G, Bates HR, Alfonso S, Cocozza M,  Porretta GC, Ballel L,  Rullas J, De Logu A, Agus E, La Rosa V, Pasca MR, De Rossi E, Wae B, Franzblau SJ, Manetti F, Botta M, Biava M  Improved BM212 MmpL3 inhibitor analogue shows efficacy in acute murine model of tuberculosis infection. Plos One, 8, e56980, 2013.
  36. Desideri N, Fioravanti R, Proietti Monaco L, Biava M, Yàñez M, Ortuso F, Alcaro S 1,5-Diphenylpenta-2,4-dien-1-ones as potent and selective monoamine oxidase-B inhibitors. Eur J Med Chem, 59, 91-100, 2013.
  37. Biava M,  Battilocchio C, Poce G, Alfonso S, Porretta GC, Consalvi S, Calderone V, Martelli A, Testai L, Ghelardini C, Di Cesare Mannelli L, Sautebin L, Rossi A, Giordani A, Patrignani P, Anzini M Improving the solubility of a new class of antiinflammatory pharmacodynamic hybrids, that release nitric oxide and inhibit Cycloxygenase-2 isoenzyme. Eur J Med Chem, 58, 287-298, 2012.
  38. Fioravanti A, Tinti A, Pascarelli A, Di Capua A, Lamboglia A, Cappelli A, Biava M, Giordani A, Niccolini S, Galeazzi M, Anzini M In vitro effects of VA441, a new selective Cyclooxygenase-2 inhibitor, on human osteoarthritic chondrocytes exposed to IL-1β. J Pharmacol Sci, 120, 6-14, 2012.
  39. Battilocchio C, Baxendale IR, Biava M, Kitching MO, Ley SVA Flow based   synthesis of 2-aminoadamantane-2-carboxilic acid. Org Process Res Dev  16, 798-810, 2012.
  40. Battilocchio C, Baumann M, Baxendale IR, Biava M, Kitching MO, Ley SV, Martin  RE, Ohnmacht SA, Tappina NDC Scale-Up of flow-assisted synthesis of C2-symmetric chiral PyBox ligands. Synthesis, 44, 635–647, 2012.
  41. La Rosa V, Poce G, Ortiz Canseco J, Buroni S, Pasca MR, Biava M, Raju RM, Porretta GC, Alfonso S, Battilocchio C, Javid B, Sorrentino F, Ioerger TR, Sacchettini JC, Manetti F,  Botta M, De Logu A, Rubin EJ MmpL3 is the cellular target of the antitubercular pyrrole derivative BM212. AAC, 56, 324–331, 2012.
  42. Biava M, Porretta GC, Poce G, Battilocchio C, Alfonso S, Rovini M, Valenti S, Giorgi G, Calderone V, Martelli A, Testai L, Sautebin L, Rossi A, Papa G, Ghelardini C, Di Cesare Mannelli L, Giordani A, Anzellotti P, Bruno A, Patrignani P, Anzini M Novel analgesic/anti-inflammatory agents: diarylpyrrole acetic esters endowed with nitric oxide releasing properties. J Med Chem, 54, 7759−7771, 2011.
  43. Radi M, Brullo C, Crespan E, Tintori C, Musumeci F, Biava M, Schenone S, Dreassi E, Zamperini C, Maga G, Pagano D, Angelucci A, Bologna M, Botta M Identification of potent c-Src inhibitors strongly affecting the proliferation of human neuroblastoma cells. Bioorg Med Chem Lett  21, 5928-5933, 2011.
  44. Schenone S, Brullo C, Musumeci F, Biava M, Falchi F, Botta M Fyn kinase in brain diseases and cancer: the search for inhibitors. Current Med Chem,  18,  2921-2942, 2011.
  45. Maccari G, Jaeger T, Moraca F, Biava M, Flohe L, Botta M A fast virtual screening approach to identify structurally diverse inhibitors of trypanothione reductase. Bioorg Med Chem Lett, 21,  5255-5258, 2011.
  46. Biava M, Porretta GC, Poce G, Battilocchio C, Botta M, Manetti F, Rovini M, Cappelli A, Sautebin L, Rossi A, Pergola C, Ghelardini C, Galeotti N, Makovec F, Giordani A, Anzellotti P, Tacconelli S, Patrignani P, Anzini M Enlarging the NSAIDs family: ether, ester and acid derivatives of the 1,5-diarylpyrrole scaffold as novel anti-inflammatory and analgesic agents. Curr Med Chem, 18, 1540-1554, 2011.
  47. Biava M, Porretta GC, Poce G, Battilocchio C, Alfonso S, De Logu A, Manetti F, Botta M Developing pyrrole-derived antimycobacterial agents: a rational lead optimization approach. ChemMedChem, 6, 593-599, 2011.
  48. Biava M, Porretta GC, Poce G, Battilocchio C, Alfonso S, De Logu A, Serra N, Manetti F, Botta M Identification of a novel pyrrole derivative endowed with antimycobacterial activity and protection index comparable to that of the current antitubercular drugs streptomycin and rifampin. Bioorg Med Chem, 18, 8076–8084, 2010.
  49. Biava M, Porretta GC, Poce G, Battilocchio C, Manetti F, Botta M, Sautebin L, Rossi A, Pergola C, Ghelardini C, Norcini M, Makovec F,  Anzellotti P, Cirilli R, Ferretti R, Patrignani P, Anzini M Novel ester and acid derivatives of the 1,5-diarylpyrrole scaffold as anti-inflammatory and analgesic agents. Synthesis, in vitro and in vivo biological evaluation. J Med Chem, 53, 723-733, 2010.

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