RESEARCH
RESEARCH
GREEN CHEMISTRY
GREEN CHEMISTRY
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.
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:
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 and indoles. In parallel, laccases have been also employed in the chemo-enzymatic synthesis of furans.
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 and indoles. 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 thio-alcohols and thio-carboxylic acids, using various enzymes such as ketoreductases and nitrilases. In addition, new biocatalytic methodologies for the synthesis of chiral sulfoxides using both oxidative and reductive biocatalysts are investigated in the group.
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 thio-alcohols and thio-carboxylic acids, using various enzymes such as ketoreductases 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 bonds. We are currently investigating new enzymes, mainly methyltransferases, as potential biocatalysts for the construction of new C-C and X-C bonds.
3) Development of new enzymes and biocatalysts for the construction of C-C bonds. We are currently investigating new enzymes, mainly methyltransferases, as potential biocatalysts for the construction of new C-C and X-C bonds.
MEDICINAL CHEMISTRY
MEDICINAL CHEMISTRY
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:
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. By means of merging of these molecular portions, new hybrid chemical entities that maintain structural elements of the parent compounds could be designed. We discovered a new class of antitubercular and antibacterial agents through the hybridization of the antitubercular agent BM212 and the drug SQ109 currently in clinical trials. New pyrrole derivatives highly active against drug resistant and intracellular M. tuberculosis were identified as well as a series of pyrroles targeting DNA gyrase in Gram bacteria.
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. By means of merging of these molecular portions, new hybrid chemical entities that maintain structural elements of the parent compounds could be designed. We discovered a new class of antitubercular and antibacterial agents through the hybridization of the antitubercular agent BM212 and the drug SQ109 currently in clinical trials. New pyrrole derivatives highly active against drug resistant and intracellular M. tuberculosis were identified as well as a series of pyrroles targeting DNA gyrase in Gram bacteria.
2) Membrane disrupting drugs. A relatively novel area of investigation in our group is the development of membrane disrupting agents. We have recently developed new membrane disrupting molecules which were designed through an hybridization approach using antibacterial guanidine compounds as templates. The new compounds have synergistic activity with classic antibiotics.
2) Membrane disrupting drugs. A relatively novel area of investigation in our group is the development of membrane disrupting agents. We have recently developed new membrane disrupting molecules which were designed through an hybridization approach using antibacterial guanidine compounds as templates. The new compounds have synergistic activity with classic antibiotics.
3) 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. Fundamentally, light is not toxic to humans and easily delivered with high precision. Several successful examples of the application of photopharmacology have been reported to date, including photoswitchable antimicrobials and antitumor therapy. We have developed new photo-CORM agents which upon activation with blue light show antibacterial and antibiofilm activity. The compounds are likely to exert their biological activity through controlled release of CO as well as the formation of antimicrobial photo-byproducts. Additional work on the development of photoactivable membrane disrupting drugs is also in progress
3) 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. Fundamentally, light is not toxic to humans and easily delivered with high precision. Several successful examples of the application of photopharmacology have been reported to date, including photoswitchable antimicrobials and antitumor therapy. We have developed new photo-CORM agents which upon activation with blue light show antibacterial and antibiofilm activity. The compounds are likely to exert their biological activity through controlled release of CO as well as the formation of antimicrobial photo-byproducts. Additional work on the development of photoactivable membrane disrupting drugs is also in progress
