Noble metal complexes with heterocyclic nitrogen ligands: application as antimicrobials

Cup: J53D23014830001

Codice MUR: P2022PZ8JE

Importo finanziato: 240.000,00 Euro

Decreto Direttoriale MUR n. 1409 del14/09/2022 - Bando PRIN 2022 PNRR - Missione 4 “Istruzione e Ricerca” del Piano Nazionale di Ripresa e Resilienza - componente C2 – investimento 1.1, Progetti di Rilevante Interesse Nazionale - PRIN

PROJECT DESCRIPTION

Antimicrobial resistance is one of the most urgent public health problems, affecting people of all ages and threatening the healthcare, agriculture and veterinary industries worldwide. Over the years, human and animal pathogens have become increasingly resistant to commonly used antibiotics and, consequently, the world is running out of antibacterials and antimycotics: although more than 20 new classes of antibiotics came onto the market in the early part of the 20th century, only two have been commercialized in recent decades. Multidrug resistance (MDR) is also of further concern. As many as 12 families of bacteria, among those at greatest risk to human health and resistant to most antibiotics, are today on the first list of "priority pathogens" drawn up by WHO (World Health Organization). Accordingly, these pathogens are classified into three categories: critical, high, and medium priority. This list was created as part of WHO's efforts to address the rising global resistance to antimicrobial medications, to direct and stimulate research and development of new antibiotics. The list also highlights the danger posed by gram-negative bacteria that are multi-antibiotic resistant. In an effort to find new classes of antibiotics, recent studies have shown that several coordination compounds of noble metals show promising  biological effects both in vitro and in vivo, deserving attention as a new class of possible antimicrobial agents.

With these premises this research proposal will be focalized in the design and synthesis of new organic, organometallic and inorganic compounds, to be screened as novel antimicrobial drugs.

The project brings together distinct and complementary expertises from three research units: the Sassari CNR Unit (CNR-ORG, organic synthesis) and the Sassari University Unit (UNISS-INORG, synthesis of inorganic and organometallic complexes) are complemented by the Cagliari University Unit (UNICA-BIO, studies of antimicrobial activity and toxicity).

The CNR-ORG Unit will carry out the synthesis of an extended series of triazole-pyridine and triazole-oxazoline based ligands while UNISS-INORG will be involved in the synthesis of bipyridine and pyridilimidazo-pyridine based ligands. With all the newly synthesized ligands the UNISS-INORG Unit will prepare a series of noble metal complexes whose properties will be tuned by an appropriate choice of the ancillary ligands.

The new compounds will be fully characterized as far as concern their chemical properties and will be tested by UNICA-BIO to evaluate: i) the activities against the WHO-listed bacteria cultured in a liquid medium and in planktonic status; ii) the antimicrobial susceptibility with the bacteria cultivated in vitro as biofilm; iii) the in vitro toxicity to determine their potential human hazardousness.

Finally, the study will aim to find structural-activity relationships and formulate concrete hypotheses on the actual mechanism of action.