RESEARCH

The main area of research in the group is the development of green and sustainable methodologies for the synthesis of drugs, drug-like compounds and chemicals, exploiting enzymes, alone or in combination with other catalysts.

We are working on three main themes:

1) Biocatalytic synthesis of heterocycles with a particular focus on the construction of heteroaromatic rings using biocatalysts. Heterocycles are privileged structures found in many drugs, natural compounds and chemicals. It has been estimated that more than 85% of all biologically active drugs contain at least one heterocyclic ring in their structures. We aim to explore new biocatalytic and chemo-enzymatic methods for the construction of heteroaromatic rings, like pyrroles, indole, furans etc. We first unveiled the ability of MAO-N enzymes to catalyse the aromatization of aliphatic 3-pyrroline precursors and later we extended our studies to the sythesis of pyridines, indoles amd quinolines. In parallel, laccases have been also employed in the chemo-enzymatic synthesis of furans.

2) Development of biocatalytic and chemo-enzymatic methodologies for the synthesis of chiral sulfur compounds. Most of the best-selling drugs contain a sulfur atom in their structure and sulfur is often used as isoster group in medicinal chemistry. Moreover, sulfur compounds may possess unique organoleptic properties finding use in flavour and fragrance industry. We are investigating new methods for the stereoselective synthesis of chiral sulfur compounds, in particular hydroxysulfides and thio-carboxylic acids, using various enzymes such as ketoreductases, ene-reductases and nitrilases. In addition, new biocatalytic methodologies for the synthesis of chiral sulfoxides using both oxidative and reductive biocatalysts are investigated in the group.

3) Development of new enzymes and biocatalysts for the construction of C-C and C-N bonds. We are currently investigating new enzymes, mainly methyltransferases, as potential biocatalysts for the construction of new C-C and X-C bonds. The group is particularly interested in the development of new biocatalysts for the synthesis of cyclopropane rings. We are also exploring new reductive enzymes for the synthesis of amine derivatives and generation of new C-N bonds.

Part of our work is in the area of antimicrobials drug design and synthesis of small molecules targeting bacteria. We try to apply the concept of sustainability to drug discovery through the identification of new strategies for the design of antimicrobials:

1) Drug hybridization strategies. The molecular hybridization approach is one of the strategies included within the rational design protocol for the identification of new biologically relevant small molecules. This approach is based on the recognition of structurally comparable or similar molecular portions of two or more bioactive compounds. This approach led to the identification of new pyrrole derivatives highly active against drug resistant and intracellular M. tuberculosis as well as Gram bacteria.

2) Photoactivable drugs. Photopharmacology is a novel approach in medicine in which the activity of drugs can be modulated with light. The energy of light is used to change the shape, conformation and chemical properties of drugs, allowing to modulate, at will, their biological activity. We have developed new photo-CORM agents which upon activation with blue light show antibacterial and antibiofilm activity. Weare currently developing new amphiphilic molecules that can act as photoactivable membrane disrupting drugs against bacteria.