The Medicinal Chemistry and Drug Discovery Group is focused on the discovery of small molecules addressing cancer and infectious diseases and has emerged from the entitled Bioorganic and Medicinal Chemistry Group at CNC. The background in design, organic synthesis and in vitro evaluation of anticancer triterpenoids, diterpenoids, flavonoids, oxysterols and steroid hormones, has provided an array of novel molecules with relevant activities in in vitro cancer models. To strengthen the quality of the research to be produced, a current strategy of the group has been the inclusion of biology researchers. Their studies in microbiology, including in vivo models, have allowed the molecular characterization of mechanisms of resistance to antibiotics. The enlargement of the group to intercept with the biology area has determined the present name of the group.
The group comprises three subgroups: (1) ML Sá e Melo’s group (2 integrated members), (2) J Salvador’s group (2 integrated members) and (3) GJ da Silva’s group (2 integrated members).
The multidisciplinary group has established collaborations with national and international groups.
The sub-group (1), headed by M L Sá e Melo, is composed by two PhD members with experience on synthesis in drug discovery, with emphasis in steroid chemistry, asymmetric synthesis and biocatalysis. Students have the opportunity to develop experimental work in other laboratories which complement our expertises. The subgroup has established collaboration with S Riva (ICRM, CNR, Milano, Italia) who is an expert in biocatalysts for selective transformations of natural compounds. The biochemical studies on enzyme inhibitors in cancer are performed in collaboration with Teresa Dinis (Molecular and Cell Toxicology, CNC, Coimbra, Portugal) and in vitro cytotoxic evaluation with human cancer cell lines is done in collaboration with JN Moreira and S Simões (Vectors and Gene Therapy, CNC, Coimbra, Portugal). Studies on new hybrid antimalarial steroids are performed in collaboration with F Lopes (IMed, FFUL, Lisboa, Portugal) for stability and toxicity and with M Prudêncio (IMM, Lisboa, Portugal) for antimalarial evaluation. Studies on the activities of estradiol derivatives in estrogen receptors, with emphasis in the GPR30 receptor, are carried out in collaboration with A Mendes (Cellular Immunology and Oncobiology, CNC, Coimbra, Portugal). Computational techniques in drug discovery and development are supported by G Colombo (Biomolecular Simulations and Computational Chemistry, ICRM, CNR, Milan, Italia) for both subgroups (1) and (2).
The sub-group (2), headed by J. Salvador, is composed by two PhD members with experience on the synthesis of triterpenic compounds with anticancer and anti-infectious activities. This sub-group also collaborates with T Dinis (CNC, Coimbra) and with G Colombo (CNR, Milano) under the expertises mentioned above. The collaboration within the group with G J da Silva, subgroup (3), supports the antibacterial activity evaluation. The collaboration with M Cascante (Univ. Barcelona, Spain) provides a strong support for the biological evaluation of new molecules against different types of cancer targets.
The sub-group (3) headed by GJ da Silva is composed by two PhD members with experience on microbial infections and molecular characterization of antimicrobial resistance. Moreover, some PhD students are gathering experience on in vivo models (cell lines), supported by members of another CNC group (J Laranjinha, C Nunes) and external groups specialized in host-microbe interactions and inflammation (J Wallace, A Buret, Canada). Other students have experience on the design of DNA microarrays and bacterial genetics to study bacterial infection with collaboration with groups of Bacteriology (M Anjum, London UK; K Nielsen, Tromso Norway). These members articulate with others from specialized groups in medicinal chemistry to contribute with biological and microbial genetics scientific knowledge.