LAUSR

Abstract We designed and synthesized three new compounds against breast cancer. The first, N-(2-hydroxyphenyl)-2-propylpentanamide (HO-AAVPA), aims to target histone deacetylase. The other two compounds, (3aS, 4R, 9bR)-4-(6-bromobenzo[d][1,3]dioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline-8-carboxylic (E)-N,N′-diisopropylcarbamimidic anhydride (ISOUREA) and (3aS, 4R, 9bR)-4-(6-bromobenzo[d][1,3]dioxol-5-yl)-5-(tert-butoxycarbonyl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline-8-carboxylic acid (G1-PABA-BOC) designed to bind to the G protein-coupled estrogen receptor. To increase the water solubility of the designed molecules, we used mixed polymeric micelles of triblock copolymer P123 and F127 as nanocarriers. We determined the water solubility, encapsulation efficiency (EE%), drug loading coefficient (DL%) and in vitro release profile of each drug loaded in the mixed polymeric micelles. We also studied the morphology and size of loaded micelles with each of the individual drugs in binary mixtures by cryo-transmission electron microscopy and dynamic light scattering. The results showed that the micelles had a spherical morphology with a size between 23 and 38 nm. The topography of the loaded micelles was studied by atomic force microscopy, and the changes in the surface were found to depend on the type of drug loaded into the mixed polymeric micelle. Finally, all solutions were tested on MDA-MB-231 and MCF-7 cancer cell lines respectively, finding antiproliferative properties for all loaded micelles in both cancer cell lines. The IC50 for the HO-AAVPA/G1-PABA-BOC mixture loaded in the micelles, was lower than the corresponding value of the compounds tested by themselves on MCF-7 cell line. We conclude that the mixed polymeric micelles are able to solubilize large quantities of the highly hydrophobic drugs used in this work and improve their antiproliferative properties.