Research, Development And Industrial Processes
Components: Prof. E. Valoti, Dr. Valentina Straniero, Dr. Lorenzo Suigo (PhD student)
External collaborator: Dr. Andrea Casiraghi
1. FtsZ inhibitors as potential wide spectrum antimicrobials
Aiming at fighting the antimicrobial resistance, an innovative potential target is the bacterial cell division process and all the related crucial proteins. Among these proteins, FtsZ (Filamentous temperature Z) plays a pivotal role, and, in this context, our research group works on the development of inhibitors, having a 2,6-difluoro-benzamide moiety. This research is conducted in collaboration with the research group of Dr. Carlo Zanotto, at the Department of Medical Biotechnology and Translational Medicine of the University of Milan. Dr. Zanotto evaluates the molecules for their antimicrobial potencies, both on S. aureus and E. coli, together with the assessment of their cytotoxicity on human MRC-5 cells. Further long existing collaborations are with Dr. Victor Sebastián-Pérez working at Exscientia and with Dr. Martina Hrast at the University of Ljubljana. Recently, also Prof. William Margolin, Texas University, and Prof. Germán Rivas, CSIC in Madrid, joined the project. The aim of these recent collaborations is the complete evaluation of the mechanism of action of the most potent FtsZ inhibitors, by using microbiological and biochemical tools.
Main publications on this topic: Straniero, V. et al, Antibiotics (Basel, Switzerland) 2021, 10 (4), 442. DOI: 10.3390/antibiotics10040442; Straniero, V. et al, ChemMedChem 2020, 15 (2), 195–209. DOI: 10.1002/cmdc.201900537; Straniero, V. et al, Antibiotics (Basel, Switzerland) 2020, 9 (4), 160. DOI: 10.3390/antibiotics9040160; Straniero, V. et al, ChemMedChem 2017, 12 (16), 1303–1318. DOI: 10.1002/cmdc.201700201; Straniero, V. et al, European journal of medicinal chemistry 2016, 120, 227–243. DOI: 10.1016/j.ejmech.2016.03.068; Chiodini, G. et al, European journal of medicinal chemistry 2015, 89, 252–265. DOI: 10.1016/j.ejmech.2014.09.100.
ERC panels: LS1_13 Early translational research and drug design; LS3_1 Cell cycle, cell division and growth; LS6_6 Infectious diseases; LS6_9 Antimicrobials, antimicrobial resistance; PE5_18 Medicinal chemistry.
2. RnpA inhibitors as potential antimicrobial agents.
Main publication on this topic: Suigo, L. et al, Antibiotics (Basel, Switzerland) 2021, 10 (4), 438. DOI: 10.3390/antibiotics10040438.
ERC panels: LS1_13 Early translational research and drug design; LS6_6 Infectious diseases; LS6_9 Antimicrobials, antimicrobial resistance; PE5_18 Medicinal chemistry.
3. α-synuclein / Synapsin III modulators as disease-modifying agents for the treatment of Parkinson’s disease.
Main publications on this topic: Casiraghi, A. et al, ChemMedChem 2020, 15 (14), 1330–1337. DOI: 10.1002/cmdc.202000128; Faustini, G. et al, Neurobiology of disease 2020, 138, 104789. DOI: 10.1016/j.nbd.2020.104789, PCT/EP2021/071717.
ERC panels: LS1_13 Early translational research and drug design; LS5_2 Glial cells and neuronal-glial communication; LS5_11 Neurological and neurodegenerative disorders; PE5_18 Medicinal chemistry.
4. Farnesyl Transferase inhibitors as antiproliferative agents.
Main publications on this topic: Straniero, V. et al, Bioorganic & medicinal chemistry letters 2014, 24 (13), 2924–2927. DOI: 10.1016/j.bmcl.2014.04.078; Bolchi, C. et al, Bioorganic & medicinal chemistry letters 2011, 21 (18), 5408–5412. DOI: 10.1016/j.bmcl.2011.07.003.
ERC panels: LS1_13 Early translational research and drug design; LS3_5 Cell signalling and signal transduction, exosome biology; LS4_12 Cancer; PE5_18 Medicinal chemistry.
5. Stereotechnologies on bioactive molecules
While working on the synthesis of several molecules, abundant is the number of compounds having one or more chiral centres, thus having different biological activities.
Is thus important to consider and study the preparation of single enantiomers, by enantio- or stereo- selective synthesis, as well as the resolution of racemic mixtures. Sometimes the study of the racemization of the distomer is required, especially for industrial processes. The evaluation of a single enantiomer, or of enantiomeric and diastereomeric systems, is possible by using different analytical techniques (spectroscopy, thermal analysis, electrophoresis, diffractometry, chromatography), and only after having a solid experience, both theoretical and practical.
Main publications on this topic: Straniero, V. et al, Chirality 2018, 30 (7), 943–950. DOI: 10.1002/chir.22968.; Casiraghi, A. et al The Journal of organic chemistry 2018, 83 (21), 13217–13227. DOI: 10.1021/acs.joc.8b02012.
ERC panels: LS1_13 Early translational research and drug design; PE5_17 Organic chemistry.