Research Groups‎ > ‎

SinFarm (CHIM/08)

Head of Laboratory: Prof.ssa Biava Mariangela

Website:


Main Topics 


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.

National and International Collaborations

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).


Facilities


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

ERC panels


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


Grants (2015-2018): 

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”




Laboratory Members:

Mariangela Biava
Giovanna Poce
Sara Consalvi
Giulia Venditti
Cristina Scarpecci

Publications 2015-2016

1. Poce, G.; Cocozza, M.; Alfonso, S.; Consalvi, S.; Venditti, G.; Fernandez-Menendez, R.; Bates, R.H.; Barros Aguirre, D.; Ballell, L.; De Logu, A.; Vistoli,  G.; Biava, M. In vivo potent BM635 analogue with improved drug-like properties.Eur. J. Med. Chem.201814, 539-550. 

2. Xua, Z.; Meshcheryakov, V. A.; Poce, G.; Chng, S. S. MmpL3 is the flippase for mycolic acids in mycobacteriaPNAS2017114, 7993-7998.

3. Poce, G.; Consalvi, S.; Cocozza, M.;  Fernandez-Menendez,  R.; Bates,  R. H.; Ortega Muro, F.; Barros Aguirre, D.;  Ballell, L.; Biava, M. Pharmaceutical salt of BM635 with Improved Bioavailability. Eur. J. Pharm. Sci. 201799, 17-23.

4. Venditti, G.; Poce, G.; Consalvi, S.; Biava, M. 1,5-Diarylpyrroles as potent antitubercular and anti-inflammatory agents, Chemistry of Heterocyclic Compounds201753, 281-291.

5. Poce, G.; Consalvi, S.; Biava, M. MmpL3 inhibitors: diverse chemical scaffolds inhibit the same target. Mini Rev. Med. Chem.201616, 1274-1283.

6. 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. Eur. J. Med. Chem.2016,109, 99–106.

7. 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. Eur. J. Med. Chem.,2016117, 292–300.

8. Consalvi, S.; Biava, M.; Poce, G. COX inhibitors: a patent review (2011 – 2014). Expert Opin. Ther. Pat. 20150, 1–15.

9. Poce, G.; Biava, M. Overcoming drug resistance for tuberculosis. Future Microbiol.201510, 1735–1741.

10. Piccaro, G.; Poce, G.; Biava, M.; Giannoni, F.; Fattorini, L. Activity of lipophilic and hydrophilic drugs against dormant and replicating Mycobacterium tuberculosis.J. Antibiot201568, 711-714.

11. Dragset, M. S.; Poce, G.; Alfonso, S.; Padilla-Benavides, T.; Ioerger, T. R.; Kaneko, T.; Sacchettini, J. C.; Biava, M.; Parish, T.; Argüello, J. M.; Steigedal, M.; Rubin, E. J. A novel antimycobacterial compound acts as an intracellular iron chelator. Antimicrob. Agents Chemother.201559, 2256-2264.

12. Consalvi, S.; Alfonso, S.; Di Capua, A.; Poce, G.; Pirolli, A.; Sabatino, M.; Ragno, R.; Anzini, M.; Sartini, S.; La Motta, 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.2015, 23, 810–820.

13. Fioravanti, R.; Desideri, N.; Biava, M.; Droghini, P.; Atzori, E.M.; 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.  201525, 2401-2404. 

14. Cheleschi, S; Pascarelli, N.A.; 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., 201528, 794-801.