The group applies the methods and tools of Physical Organic Chemistry and Medicinal Chemistry to investigate structure/reactivity/activity relationships of selected compounds from biologically relevant chemotypes: endoperoxydes, quinolones, tetrazoles and saccharins. We aim to contribute to the elucidation of interactions between compounds and their biological targets, thereby gathering instrumental information for rational drug design and optimization.
Topic 1. Development of anti-infective agents comprising quinolone- or peroxide-based heterocycles.
We investigate structural requirements of 4-oxoquinoline-3-esters for inhibition of the bc1 complex (respiratory chain) of Plasmodium falciparum (CQ-sensitive and multiresistant strains). Selected 2-substituted-4-oxoquinolines prepared exhibit potent activity against Mycobacterium tuberculosis.
Inspired in the antimalarial drug Artemisinin, a natural product, we develop synthetic endoperoxides with improved pharmacologic profile. We consider exploring peroxides inspired in Plakortin, a peroxide-based metabolite obtained from the marine sponge Plakortis halichondrioides.
We scrutinize the potencial of endoperoxides against other protozoans: Leishmania donovani, Perkinsus olseni, and Amyloodinium ocellatum the causative agents of Leishmaniases (in mamals), Perkinsosis (in bivalves) and Amyloodinium ocellatum (in fish), respectively.
Topic 2. Synthesis, reactivity and applications of chelants derived from tetrazole and saccharin.
We develop tetrazole-saccharyl conjugates as selective chelants and scrutinise their potential in catalysis, environmental remediation, medicine and in the design of supramolecular frameworks.
We demonstrated their utility as ligands for divalent cations. Selected copper complexes act as effective catalysts for oxidation of secondary alcohols and have shown potent cytotoxicity against adherent cancer cell lines.