Developed a new small molecule with great analgesic and antitumor potential. This is the result, at basic research level so far, of the multidisciplinary work of three departments of the University of Florence, recently published in the Journal of Medicinal Chemistry (DOI: 10.1021 / acs.jmedchem.7b01237).
The research was coordinated by Cristina Nativi (Department of Chemistry) in collaboration with Claudiu Supuran (Neurosciences, Phychology, Drug Research and Child Health - NEUROFARBA), Marco Fragai (CERM, Department of Chemistry) and involved the ElettroBioLab laboratory managed by Francesco Tadini-Buoninsegni (Department of Chemistry), the group of Carla Ghelardini (Neurofarba) and Paola Chiarugi (Department of Biomedical, Experimental and Clinical Sciences).
Through teamwork and complementary skills, these scientists have demonstrated on animal models the unique properties of the ADM_12 molecule, a lipoic acid derivative, a natural compound with antioxidant qualities.
"ADM_12, which is extremely water-soluble and non-toxic, reduces or eliminates the pain induced by chemotherapy drugs, such as oxaliplatin," explains Cristina Nativi.
"This is of extreme interest because neuropathic pain, especially that caused by chemotherapy, is considered highly disabling and difficult to treat, as there is currently no satisfactory pharmacological remedy."
But this study has also shown that the analgesic action of ADM_12 is associated with a second effect: reducing the aggressiveness of pancreatic cancer cells. "ADM_12 - continues Native - inhibits the metalloprotein carbonic anhydrase IX (CAIX), which is widely recognized as a drug target in cancer pathologies, since it modulates some of the biochemical processes at the base of metastatic processes."
The ADM_12 molecule, synthesized in the laboratory run by Cristina Nativi, is the subject of a European Patent, of which the University is co-owner, together with the inventors Nativi, Carla Ghelardini and Giancarlo la Marca (Department of Biomedical and Clinical Sciences). "The patent - Nativi explains - is currently licensed to an American start-up that collaborates with us on developing the molecule.
This important outcome, of an ongoing research project, has been made possible thanks to the generous contributions of the Cassa di Risparmio di Firenze Foundation, Banca CR Firenze and the Istituto Toscano Tumori."
In this video the young scientists Lorenzo di Cesare Mannelli, from the pharmacology team, and Oscar Francesconi, from the organic synthesis group explain the key points of the project