MOLECULARLY IMPRINTED POLYMERS: TOWARDS RECEPTOR MIMICS FOR DRUG DISCOVERY

Molecularly Imprinted Polymers (MIPs) are based on selective recognition properties of synthetic cross-linked materials possessing cavities complementary to a template molecule in size, shape and position of the functional groups. In recent years, MIPs received an increasing attention in the field of natural products for their application in the drug discovery process. In this work, new synthesis strategies were developed to obtain imprinted cavities able to mimic the flexibility and mobility exhibited by receptor/enzyme binding pockets. For the study of working conditions, Quercetin (Qu) was chosen as a representative template considering it is one of the most active compounds in the flavonoids family, commonly found in medicinal and food herbal products. Bulk polymerization (BP), precipitation polymerization (PP) and suspension polymerization (SP) were investigated to obtain optimal chromatographic materials. The Qu MIPs (Fig. 1) were evaluated as sorbents for SPE and HPLC in order to confirm the presence of imprinted cavities and to evaluate their selectivity, respectively. By SPE, successful imprinting of the MIPs is confirmed when the retention appears distinctly superior on MIPs than on NIPs (Corresponding control polymers or non-imprinted polymers). The best SPE results were obtained for MIPs prepared by the SP method. Micrographs obtained by SEM reveal the large distribution of sizes and the irregular shape of particles prepared by BP. On the contrary, spherical beads with a well-controlled size distribution were obtained by SP indicating better perspectives for their use in chromatography. The MIPs were packed into HPLC columns in order to study their selectivity towards a set of analogues and non-analogues of quercetin. Thanks to the improved chromatographic efficiency afforded by SP, the developed MIPs are highly promising for the screening of lead compounds from complex systems such as natural products.