Dipartimento di Scienza e Tecnologia del Farmaco

List and description of national scientific collaborations.    

1. Houshmand, M.; Vitale, N.;  Orso, F.;  Cignetti, A.;  Molineris, I.;  Gaidano, V.;  Sainas, S.;  Giorgis, M.;  Boschi, D.;  Fava, C.;  Passoni, A.;  Gai, M.;  Geuna, M.;  Sora, F.;  Iurlo, A.;  Abruzzese, E.;  Breccia, M.;  Mulas, O.;  Caocci, G.;  Castagnetti, F.;  Taverna, D.;  Oliviero, S.;  Pane, F.;  Lolli, M. L.;  Circosta, P.; Saglio, G., Dihydroorotate dehydrogenase inhibition reveals metabolic vulnerability in chronic myeloid leukemia. Cell Death & Disease 2022, 13 (6), 576.
2. Galati, S.; Sainas, S.;  Giorgis, M.;  Boschi, D.;  Lolli, M. L.;  Ortore, G.;  Poli, G.; Tuccinardi, T., Identification of Human Dihydroorotate Dehydrogenase Inhibitor by a Pharmacophore-Based Virtual Screening Study. Molecules 2022, 27 (12).
3. Pippione, A. C.; Kilic-Kurt, Z.;  Kovachka, S.;  Sainas, S.;  Rolando, B.;  Denasio, E.;  Pors, K.;  Adinolfi, S.;  Zonari, D.;  Bagnati, R.;  Lolli, M. L.;  Spyrakis, F.;  Oliaro-Bosso, S.; Boschi, D., New aldo-keto reductase 1C3 (AKR1C3) inhibitors based on the hydroxytriazole scaffold. Eur J Med Chem 2022, 237, 114366.
4. Rubin, E.; Pippione, A. C.;  Boyko, M.;  Einaudi, G.;  Sainas, S.;  Collino, M.;  Cifani, C.;  Lolli, M. L.;  Abu-Freha, N.;  Kaplanski, J.;  Boschi, D.; Azab, A. N., A New NF-κB Inhibitor, MEDS-23, Reduces the Severity of Adverse Post-Ischemic Stroke Outcomes in Rats. Brain Sciences 2022, 12 (1), 35.
5. Calistri, A.; Luganini, A.;  Mognetti, B.;  Elder, E.;  Sibille, G.;  Conciatori, V.;  Del Vecchio, C.;  Sainas, S.;  Boschi, D.;  Montserrat, N.;  Mirazimi, A.;  Lolli, M. L.;  Gribaudo, G.; Parolin, C., The New Generation hDHODH Inhibitor MEDS433 Hinders the In Vitro Replication of SARS-CoV-2 and Other Human Coronaviruses. Microorganisms 2021, 9 (8), 1731.
6. Sainas, S.; Giorgis, M.;  Circosta, P.;  Gaidano, V.;  Bonanni, D.;  Pippione, A. C.;  Bagnati, R.;  Passoni, A.;  Qiu, Y.;  Cojocaru, C. F.;  Canepa, B.;  Bona, A.;  Rolando, B.;  Mishina, M.;  Ramondetti, C.;  Buccinnà, B.;  Piccinini, M.;  Houshmand, M.;  Cignetti, A.;  Giraudo, E.;  Al-Karadaghi, S.;  Boschi, D.;  Saglio, G.; Lolli, M. L., Targeting Acute Myelogenous Leukemia Using Potent Human Dihydroorotate Dehydrogenase Inhibitors Based on the 2-Hydroxypyrazolo[1,5-a]pyridine Scaffold: SAR of the Biphenyl Moiety. J. Med. Chem. 2021, 64 (9), 5404-5428.
7. Luganini, A.; Sibille, G.;  Mognetti, B.;  Sainas, S.;  Pippione, A. C.;  Giorgis, M.;  Boschi, D.;  Lolli, M. L.; Gribaudo, G., Effective deploying of a novel DHODH inhibitor against herpes simplex type 1 and type 2 replication. Antiviral Research 2021, 189, 105057.
8. Peraldo-Neia, C.; Ostano, P.;  Mello-Grand, M.;  Guana, F.;  Gregnanin, I.;  Boschi, D.;  Oliaro-Bosso, S.;  Pippione, A. C.;  Carenzo, A.;  De Cecco, L.;  Cavalieri, S.;  Micali, A.;  Perrone, F.;  Averono, G.;  Bagnasacco, P.;  Dosdegani, R.;  Masini, L.;  Krengli, M.;  Aluffi-Valletti, P.;  Valente, G.; Chiorino, G., AKR1C3 is a biomarker and druggable target for oropharyngeal tumors. Cell Oncol (Dordr) 2021, 44 (2), 357-372.
9. Gaidano, V.; Houshmand, M.;  Vitale, N.;  Carrà, G.;  Morotti, A.;  Tenace, V.;  Rapelli, S.;  Sainas, S.;  Pippione, A. C.;  Giorgis, M.;  Boschi, D.;  Lolli, M. L.;  Cilloni, D.;  Cignetti, A.;  Saglio, G.; Circosta, P., The Synergism between DHODH Inhibitors and Dipyridamole Leads to Metabolic Lethality in Acute Myeloid Leukemia. Cancers (Basel) 2021, 13 (5).
10. Sainas, S.; Pippione, A. C.;  Boschi, D.; Lolli, M. L., Chapter Five - Hydroxyazoles as acid isosteres and their drug design applications—Part 1: Monocyclic systems. In Advances in Heterocyclic Chemistry, Meanwell, N. A.; Lolli, M. L., Eds. Academic Press: 2021; Vol. 134, pp 185-272.
11. Pippione, A. C.; Sainas, S.;  Boschi, D.; Lolli, M. L., Chapter Six - Hydroxyazoles as acid isosteres and their drug design applications—Part 2: Bicyclic systems. In Advances in Heterocyclic Chemistry, Meanwell, N. A.; Lolli, M. L., Eds. Academic Press: 2021; Vol. 134, pp 273-311.
12. Sainas, S.; Pippione, A. C.;  Giraudo, A.;  Martina, K.;  Bosca, F.;  Rolando, B.;  Barge, A.;  Ducime, A.;  Federico, A.;  Grossert, S. J.;  White, R. L.;  Boschi, D.; Lolli, M. L., Regioselective N-Alkylation of Ethyl 4-Benzyloxy-1,2,3-triazolecarboxylate: A Useful Tool for the Synthesis of Carboxylic Acid Bioisosteres. J. Heterocycl. Chem. 2019, 56 (1), 19.
13. Pippione, A. C.; Sainas, S.;  Goyal, P.;  Fritzson, I.;  Cassiano, G. C.;  Giraudo, A.;  Giorgis, M.;  Tavella, T. A.;  Bagnati, R.;  Rolando, B.;  Caing-Carlsson, R.;  Costa, F. T. M.;  Andrade, C. H.;  Al-Karadaghi, S.;  Boschi, D.;  Friemann, R.; Lolli, M. L., Hydroxyazole scaffold-based Plasmodium falciparum dihydroorotate dehydrogenase inhibitors: Synthesis, biological evaluation and X-ray structural studies. Eur J Med Chem 2019, 163, 266-280.
14. Boschi, D.; Pippione, A. C.;  Sainas, S.; Lolli, M. L., Dihydroorotate dehydrogenase inhibitors in anti-infective drug research. European Journal of Medicinal Chemistry 2019, 183, 111681.
15. Giraudo, A.; Krall, J.;  Bavo, F.;  Nielsen, B.;  Kongstad, K. T.;  Rolando, B.;  De Blasio, R.;  Gloriam, D. E.;  Loftier, R.;  Thiesen, L.;  Harpsoe, K.;  Frydenvang, K.;  Boschi, D.;  Wellendorph, P.;  Lolli, M. L.;  Jensen, A. A.; Frolund, B., Five-Membered N-Heterocyclic Scaffolds as Novel Amino Bioisosteres at gamma-Aminobutyric Acid (GABA) Type A Receptors and GABA Transporters. J. Med. Chem. 2019, 62 (12), 5797-5809.
16. Santos, A. R. N.; Sheldrake, H. M.;  Ibrahim, A. I. M.;  Danta, C. C.;  Bonanni, D.;  Daga, M.;  Oliaro-Bosso, S.;  Boschi, D.;  Lolli, M. L.; Pors, K., Exploration of 2+2+2 cyclotrimerisation methodology to prepare tetrahydroisoquinoline-based compounds with potential aldo-keto reductase 1C3 target affinity. Medchemcomm 2019, 10 (8), 1476-1480.
17. Sainas, S.; Temperini, P.;  Farnsworth, J. C.;  Yi, F.;  Mollerud, S.;  Jensen, A. A.;  Nielsen, B.;  Passoni, A.;  Kastrup, J. S.;  Hansen, K. B.;  Boschi, D.;  Pickering, D. S.;  Clausen, R. P.; Lolli, M. L., Use of the 4-Hydroxytriazole Moiety as a Bioisosteric Tool in the Development of Ionotropic Glutamate Receptor Ligands. J. Med. Chem. 2019, 62 (9), 4467-4482.
18. Lolli, M. L.; Carnovale, I. M.;  Pippione, A. C.;  Wahlgren, W. Y.;  Bonanni, D.;  Marini, E.;  Zonari, D.;  Gallicchio, M.;  Boscaro, V.;  Goyal, P.;  Friemann, R.;  Rolando, B.;  Bagnati, R.;  Adinolfi, S.;  Oliaro-Bosso, S.; Boschi, D., Bioisosteres of Indomethacin as Inhibitors of Aldo-Keto Reductase 1C3 (AKR1C3). ACS Med. Chem. Lett. 2019.
19. Pippione, A. C.; Sainas, S.;  Goyal, P.;  Fritzson, I.;  Cassiano, G. C.;  Giraudo, A.;  Giorgis, M.;  Tavella, T. A.;  Bagnati, R.;  Rolando, B.;  Caing-Carlsson, R.;  Costa, F. T. M.;  Andrade, C. H.;  Al-Karadaghi, S.;  Boschi, D.;  Friemann, R.; Lolli, M. L., Hydroxyazole scaffold-based Plasmodium falciparum dihydroorotate dehydrogenase inhibitors: Synthesis, biological evaluation and X-ray structural studies. Eur. J. Med. Chem. 2018, 163, 266-280.
20. Sainas, S.; Dosio, F.;  Boschi, D.; Lolli, M. L., Targeting Human Onchocerciasis: Recent Advances Beyond Ivermectin. In Neglected Diseases: Extensive Space for Modern Drug Discovery, Botta, M., Ed. Elsevier Academic Press Inc: San Diego, 2018; Vol. 51, pp 1-38.
21. Giraudo, A.; Krall, J.;  Nielsen, B.;  Sorensen, T. E.;  Kongstad, K. T.;  Rolando, B.;  Boschi, D.;  Frolund, B.; Lolli, M. L., 4-Hydroxy-1,2,3-triazole moiety as bioisostere of the carboxylic acid function: a novel scaffold to probe the orthosteric gamma-aminobutyric acid receptor binding site. Eur. J. Med. Chem. 2018, 158, 311-321.
22. Sainas, S.; Pippione, A. C.;  Boschi, D.;  Gaidano, V.;  Circosta, P.;  Cignetti, A.;  Dosio, F.; Lolli, M. L., DHODH inhibitors and leukemia: an emergent interest for new myeloid differentiation agents. Drugs Future 2018, 43 (11), 823-834.
23. Grossert, J. S.; Boschi, D.;  Lolli, M. L.; White, R. L., Fragmentation pathways arising from protonation at different sites in aminoalkyl-substituted 3-hydroxy-1,2,5-oxadiazoles (3-hydroxyfurazans). Rapid Commun. Mass Spectrom. 2018, 32 (16), 1403-1413.
24. Sainas, S.; Pippione, A. C.;  Lupino, E.;  Giorgis, M.;  Circosta, P.;  Gaidano, V.;  Goyal, P.;  Bonanni, D.;  Rolando, B.;  Cignetti, A.;  Ducime, A.;  Andersson, M.;  Järvå, M.;  Friemann, R.;  Piccinini, M.;  Ramondetti, C.;  Buccinnà, B.;  Al-Karadaghi, S.;  Boschi, D.;  Saglio, G.; Lolli, M. L., Targeting Myeloid Differentiation Using Potent 2-Hydroxypyrazolo[1,5-a]pyridine Scaffold-Based Human Dihydroorotate Dehydrogenase Inhibitors. J. Med. Chem. 2018, 61 (14), 6034-6055.
25. Pippione, A. C.; Sainas, S.;  Federico, A.;  Lupino, E.;  Piccinini, M.;  Kubbutat, M.;  Contreras, J. M.;  Morice, C.;  Barge, A.;  Ducime, A.;  Boschi, D.;  Al-Karadaghi, S.; Lolli, M. L., N-Acetyl-3-aminopyrazoles block the non-canonical NF-kB cascade by selectively inhibiting NIK. Medchemcomm 2018, 9 (6), 963-968.
26. Pippione, A. C.; Carnovale, I. M.;  Bonanni, D.;  Sini, M.;  Goyal, P.;  Marini, E.;  Pors, K.;  Adinolfi, S.;  Zonari, D.;  Festuccia, C.;  Wahlgren, W. Y.;  Friemann, R.;  Bagnati, R.;  Boschi, D.;  Oliaro-Bosso, S.; Lolli, M. L., Potent and selective aldo-keto reductase 1C3 (AKR1C3) inhibitors based on the benzoisoxazole moiety: application of a bioisosteric scaffold hopping approach to flufenamic acid. Eur. J. Med. Chem. 2018, 150, 930-945.
27. Lolli, M. L.; Sainas, S.;  Pippione, A. C.;  Giorgis, M.;  Boschi, D.; Dosio, F., Use of human Dihydroorotate Dehydrogenase (hDHODH) Inhibitors in Autoimmune Diseases and New Perspectives in Cancer Therapy. Recent. Pat. Anticancer Drug Discov. 2018, 13 (1), 86-105.
28. Pippione, A. C.; Boschi, D.;  Pors, K.;  Oliaro-Bosso, S.; Lolli, M. L., Androgen-AR axis in primary and metastatic prostate cancer: chasing steroidogenic enzymes for therapeutic intervention. J. Cancer Metastasis Treat. 2017, 3 (12), 328-61.
29. Pippione, A. C.; Giraudo, A.;  Bonanni, D.;  Carnovale, I. M.;  Marini, E.;  Cena, C.;  Costale, A.;  Zonari, D.;  Pors, K.;  Sadiq, M.;  Boschi, D.;  Oliaro-Bosso, S.; Lolli, M. L., Hydroxytriazole derivatives as potent and selective aldo-keto reductase 1C3 (AKR1C3) inhibitors discovered by bioisosteric scaffold hopping approach. Eur. J. Med. Chem. 2017, 139 (Supplement C), 936-946.
30. Pippione, A. C.; Federico, A.;  Ducime, A.;  Sainas, S.;  Boschi, D.;  Barge, A.;  Lupino, E.;  Piccinini, M.;  Kubbutat, M.;  Contreras, J.-M.;  Morice, C.;  Al-Karadaghi, S.; Lolli, M. L., 4-Hydroxy-N-[3,5-bis(trifluoromethyl)phenyl]-1,2,5-thiadiazole-3-carboxamide: a novel inhibitor of the canonical NF-[small kappa]B cascade. MedChemComm 2017, 8, 1850 - 1855.
31. Sainas, S.; Pippione, A. C.;  Giorgis, M.;  Lupino, E.;  Goyal, P.;  Ramondetti, C.;  Buccinnà, B.;  Piccinini, M.;  Braga, R. C.;  Andrade, C. H.;  Andersson, M.;  Moritzer, A.-C.;  Friemann, R.;  Mensa, S.;  Al-Karadaghi, S.;  Boschi, D.; Lolli, M. L., Design, synthesis, biological evaluation and X-ray structural studies of potent human dihydroorotate dehydrogenase inhibitors based on hydroxylated azole scaffolds. Eur. J. Med. Chem. 2017, 129, 287-302.
32. Pippione, A. C.; Dosio, F.;  Ducime, A.;  Federico, A.;  Martina, K.;  Sainas, S.;  Frølund, B.;  Gooyit, M.;  Janda, K. D.;  Boschi, D.; Lolli, M. L., Substituted 4-hydroxy-1,2,3-triazoles: synthesis, characterization and first drug design applications through bioisosteric modulation and scaffold hopping approaches. MedChemComm 2015, 6 (7), 1285-1292.
33. Grossert, J. S.; Pippione, A. C.;  Boschi, D.;  Lolli, M. L.; White, R. L., Heterocyclic ring cleavage upon collision-induced dissociation of deprotonated 3-hydroxy-1,2,5-oxadiazoles (3-hydroxyfurazans). J. Mass Spectrom. 2015, 50 (12), 1433-1437.
34. Chegaev, K.; Lazzarato, L.;  Tamboli, Y.;  Boschi, D.;  Blangetti, M.;  Scozzafava, A.;  Carta, F.;  Masini, E.;  Fruttero, R.;  Supuran, C. T.; Gasco, A., Furazan and furoxan sulfonamides are strong alpha-carbonic anhydrase inhibitors and potential antiglaucoma agents. Bioorg. Med. Chem. 2014, 22 (15), 3913-3921.
35. Boschi, D.; Tosco, P.;  Chandra, N.;  Chaurasia, S.;  Fruttero, R.;  Griffin, R.;  Wang, L. Z.; Gasco, A., 6-Cyclohexylmethoxy-5-(cyano-NNO-azoxy)pyrimidine-4-amine: A new scaffold endowed with potent CDK2 inhibitory activity. Eur. J. Med. Chem. 2013, 68, 333-338.
36. Boschi, D.; Guglielmo, S.;  Aiello, S.;  Morace, G.;  Borghi, E.; Fruttero, R., Synthesis and in vitro antimicrobial activities of new (cyano-NNO-azoxy)pyrazole derivatives. Bioorg. Med. Chem. Lett. 2011, 21 (11), 3431-3434.
37. Gerace, E.; Salomone, A.;  Fasano, F.;  Costa, R.;  Boschi, D.;  Di Stilo, A.; Vincenti, M., Validation of a GC/MS method for the detection of two quinolinone-derived selective androgen receptor modulators in doping control analysis. Anal. Bioanal. Chem. 2011, 400 (1), 137-144.
38. Boschi, D.; Giorgis, M.;  Cena, C.;  Talniya, N. C.;  Di Stilo, A.;  Morini, G.;  Coruzzi, G.;  Guaita, E.;  Fruttero, R.; Gasco, A., Multitarget Drugs: Synthesis and Preliminary Pharmacological Characterization of Zileuton Analogues Endowed with Dual 5-LO Inhibitor and NO-Dependent Activities. ChemMedChem 2010, 5 (9), 1444-1449.
39. Boschi, D.; Cena, C.;  Di Stilo, A.;  Rolando, B.;  Manzini, P.;  Fruttero, R.; Gasco, A., Nitrooxymethyl-Substituted Analogues of Rofecoxib: Synthesis and Pharmacological Characterization. Chem. Biodiversity 2010, 7 (5), 1173-1182.
40. Bozzo, F.; Bassignana, A.;  Lazzarato, L.;  Boschi, D.;  Gasco, A.;  Bocca, C.; Miglietta, A., Novel nitro-oxy derivatives of celecoxib for the regulation of colon cancer cell growth. Chemico-Biological Interactions 2009, 182 (2-3), 183-190.
41. Boschi, D.; Lazzarato, L.;  Rolando, B.;  Filieri, A.;  Cena, C.;  Di Stilo, A.;  Fruttero, R.; Gasco, A., Nitrooxymethyl-Substituted Analogues of Celecoxib: Synthesis and Pharmacological Characterization. Chem. Biodiversity 2009, 6 (3), 369-379.
42. Gasco, A.; Boschi, D.;  Chegaev, K.;  Cena, C.;  Di Stilo, A.;  Fruttero, R.;  Lazzarato, L.;  Rolando, B.; Tosco, P., Multitarget drugs: Focus on the NO-donor hybrid drugs. Pure and Applied Chemistry 2008, 80 (8), 1693-1701.
43. Boschi, D.; Tron, G. C.;  Lazzarato, L.;  Chegaev, K.;  Cena, C.;  Di Stilo, A.;  Giorgis, M.;  Bertinaria, M.;  Fruttero, R.; Gasco, A., NO-donor phenols: A new class of products endowed with antioxidant and vasodilator properties. J. Med. Chem. 2006, 49 (10), 2886-2897.
44. Cena, C.; Bertinaria, M.;  Boschi, D.;  Giorgis, M.; Gasco, A., Use of the furoxan (1,2,5-oxadiazole 2-oxide) system in the design of new NO-donor antioxidant hybrids. ARKIVOC 2006, 7, 301-309.
45. Del Grosso, E.; Boschi, D.;  Lazzarato, L.;  Cena, C.;  Di Stilo, A.;  Fruttero, R.;  Moro, S.; Gasco, A., The furoxan system: Design of selective nitric oxide (NO) donor inhibitors of COX-2 endowed with anti-aggregatory and vasodilating activities. Chem. Biodiversity 2005, 2 (7), 886-900.
46. Cena, C.; Boschi, D.;  Tron, G. C.;  Chegaev, K.;  Lazzarato, L.;  Di Stilo, A.;  Aragno, M.;  Fruttero, R.; Gasco, A., Development of a new class of potential antiatherosclerosis agents: NO-donor antioxidants. Bioorg. Med. Chem. Lett. 2004, 14 (24), 5971-5974.
47. Boschi, D.; Tron, G. C.;  Di Stilo, A.;  Fruttero, R.;  Gasco, A.;  Poggesi, E.;  Motta, G.; Leonardi, A., New potential uroselective NO-Donor alpha(1)-antagonists. J. Med. Chem. 2003, 46 (17), 3762-3765.
48. Boschi, D.; Sorba, G.;  Bertinaria, M.;  Fruttero, R.;  Calvino, R.; Gasco, A., Unsymmetrically substituted furoxans. Part 18. Smiles rearrangement in furoxan systems and in related furazans. J. Chem. Soc., Perkin Trans. 1 2001,  (15), 1751-1757.
49. Boschi, D.; Caron, G.;  Visentin, S.;  Di Stilo, A.;  Rolando, B.;  Fruttero, R.; Gasco, A., Searching for balanced hybrid NO-donor 1,4-dihydropyridines with basic properties. Pharm. Res. 2001, 18 (7), 987-991.
50. Boschi, D.; Cena, C.;  Fruttero, R.;  Brenciaglia, M. I.;  Scaltrito, M. M.;  Dubini, F.; Gasco, A., Activity of calvatic acid and its analogs against Helicobacter pylori. Pharmazie 2001, 56 (8), 670-672.
51. Visentin, S.; Ermondi, G.;  Boschi, D.;  Grosa, G.;  Fruttero, R.; Gasco, A., Thermolysis of 4-(2-azido-3-nitrophenyl)-1,4-dihydropyridines as source of beta-carboline derivatives and some related compounds. Tetrahedron Lett. 2001, 42 (27), 4507-4510.
52. Cena, C.; Visentin, S.;  Di Stilo, A.;  Boschi, D.;  Fruttero, R.; Gasco, A., Studies on agents with mixed NO-dependent and calcium channel antagonistic vasodilating activities. Pharm. Res. 2001, 18 (2), 157-165.
53. Boschi, D.; Cena, C.;  Di Stilo, A.;  Fruttero, R.; Gasco, A., Nicorandil analogues containing NO-donor furoxans and related furazans. Bioorg. Med. Chem. 2000, 8 (7), 1727-1732.
54. Ermondi, G.; Visentin, S.;  Boschi, D.;  Fruttero, R.; Gasco, A., Structural investigation of Ca2+ antagonists benzofurazanyl and benzofuroxanyl-1,4-dihydropyridines. J. Mol.  Struct. 2000, 523, 149-162.
55. Caron, G.; Ermondi, G.;  Boschi, D.;  Carrupt, P. A.;  Fruttero, R.;  Testa, B.; Gasco, A., Structure-property relationships in the basicity and lipophilicity of arylalkylamine oxides. Helv. Chim. Acta 1999, 82 (10), 1630-1639.
56. Visentin, S.; Amiel, P.;  Fruttero, R.;  Boschi, D.;  Roussel, C.;  Giusta, L.;  Carbone, E.; Gasco, A., Synthesis and voltage-clamp studies of methyl 1,4-dihydro-2,6-dimethyl-5-nitro-4-(benzofurazanyl)pyridine-3-carboxylat e racemates and enantiomers and of their benzofuroxanyl analogues. J. Med. Chem. 1999, 42 (8), 1422-1427.
57. Ermondi, G.; Boschi, D.;  Di Stilo, A.;  Tironi, C.; Gasco, A., Pyrazole analogues of prazosin. Farmaco 1998, 53 (7), 519-524.
58. Fruttero, R.; Boschi, D.;  Fornatto, E.;  Serafino, A.;  Gasco, A.; Exner, O., Electronic substituent effects of furoxan and furazan systems. J. Chem. Res., Synop. 1998,  (9), 495-495A.
59. Fruttero, R.; Caron, G.;  Fornatto, E.;  Boschi, D.;  Ermondi, G.;  Gasco, A.;  Carrupt, P. A.; Testa, B., Mechanisms of liposomes/water partitioning of (p-methylbenzyl)alkylamines. Pharm. Res. 1998, 15 (9), 1407-1413.
60. Gasco, A. M.; Boschi, D.;  Di Stilo, A.;  Medana, C.;  Gasco, A.;  Martorana, P. A.; Schonafinger, K., Characterisation of furoxancarbonitriles as a new class of vasodilators. Arzneimittelforschung 1998, 48 (3), 212-218.
61. Boschi, D.; Di Stilo, A.;  Cena, C.;  Lolli, M.;  Fruttero, R.; Gasco, A., Studies on agents with mixed NO-dependent vasodilating and beta-blocking activities. Pharm. Res. 1997, 14 (12), 1750-1758.
62. Antonini, G.; Pitari, G.;  Caccuri, A. M.;  Ricci, G.;  Boschi, D.;  Fruttero, R.;  Gasco, A.; Ascenzi, P., Inhibition of human placenta glutathione transferase P1-1 by the antibiotic calvatic acid and its diazocyanide analogue - Evidence for multiple catalytic intermediates. Eur. J. Biochem.

 1997, 245 (3), 663-667.

63. Fruttero, R.; Boschi, D.;  Di Stilo, A.; Gasco, A., The Furoxan System as a Useful Tool to Balancing "Hybrids" with mixed alfa1-Antagonist and NO-Like Vasodilator Activities. J. Med. Chem. 1995, 38, 4944-4949.
64. Gasco, A. M.; Boschi, D.; Gasco, A., Unsymmetrically Substituted Furoxan. Part 15. Bromination of Dimethylfuroxan and Related Compounds with NBS. J. Heterocycl. Chem. 1995, 32, 811-813.
65. Boschi, D.; Di Stilo, A.;  Fruttero, R.;  Medana, C.;  Sorba, G.; Gasco, A., α 1-Adrenoceptor Blocking Activity of Some Ring-open Analogues of Prazosin. Arch. Pharm. 1994, 327, 661-667.
66. Di Stilo, A.; Fruttero, R.;  Boschi, D.;  A.M., G.;  Sorba, G.;  Gasco, A.; Orsetti, M., Use of Nitric Oxide Releasing Furoxan System in the Design of "Hybrids": Substitution of Furoxan Moieties for the Furan Ring in Prazosin. Med. Chem. Res. 1993, 3, 554-566.

Cancer Drug Discovery Workshop

English

Dr Klaus Pors, Senior Lecturer in Chemical Biology

Institute of Cancer Therapeutics, University of Bradford, U.K.

New Antitumour Imidazotetrazine
Prodrugs

Professor Richard T. Wheelhouse
PhD CChem FRSC
Invited Lecturer inside Teaching Staff Mobility
Erasmus Programme
Bradford School of Pharmacy
University of Bradford

pfDHODH in Malaria targeting. Targeting pfDHODH is claimed to be one of the hottest target for future Malaria treatment. One of recent biological targets which have been proposed for targeting Plasmodium Falciparum, the parasites responsable of Malaria, is DHODH (pfDHODH) (see here). This essential mitochondrial enzyme catalyzes the flavin mononucleotide-dependent formation of orotic acid, a key step in de novo pyrimidine biosynthesis. Unlike mammalian cells, pyrimidine biosynthesis is indispensible to parasites as they are unable to salvage preformed pyrimidine bases and nucleosides and rely entirely on de novo synthesis. Although this key, rate-limiting enzyme involved in de novo pyrimidine synthesis, Plasmodium DHODH awaits validation as a clinical target. However, since Malaria parasites are unable to salvage pyrimidines and it is located on the inner membrane of the mitochondrion and intimately connected with the electron transport chain, the site of action of atovaquone, it would be amazing if this is not eventually forthcoming.  In collaboration with groups at the Lund University, we are developing new pfDHODH inhibitors.

NF-κB as a therapeutic target for cancer. Protein kinases are involved in the control of a large number of cellular processes and play a central role in human physiology. Deficiency in kinase activity has implications in cancer, central nervous system disorders, autoimmune diseases and immunosuppression, diabetes, osteoporosis and various metabolic disorders. Small-molecule kinase inhibitors have therefore moved into the focus of the pharmaceutical industry as a new class of drugs, which is expected to produce new and more efficient treatments and grow significantly within the coming decade. We are creating a new platform for lead compound discovery with a focus on protein kinases. Three kinases will be targeted for the development of inhibitory compounds: IKKa, IKKb and NIK.