Resumen de New methodologies for the generation of spirooxindoles and their application to the synthesis of natural products and biologically active compounds
The spiro[pyrrolidine-3,3'-oxindole] framework that presents in various natural products often displays interesting biological activities. Therefore, in order to develop new strategies towards the spiro derivatives, a number of studies have been carrying out in the last years. In the context of COST Action CM1407 “Challenging Organic Synthesis Inspired by Nature: from Natural Products Chemistry to Drug Discovery”, our research group sent some diversely substituted spiro compounds to the Karolinska Institute in Stockholm to be tested. When the compounds were used to examine binding and inhibition regarding to cysteine kinase (CysM) of mycobacterium tuberculosis (Mtb), high-throughput screening of our first COST Natural Product Compound Collection resulted in some hits, being one of them, compound MP23 (see Figure 1). This compound was a potential hit candidate for further exploration but showed weak binding affinities before in vivo assays would be appropriate. When we compared the first hit candidate MP23 with some closely related derivatives which were found inactive, we made some general conclusions about the influences of structural characteristics on biological activity. These outcomes are described in the following Figure.
