Poly(amidoamine)s synthesis, characterisation and interaction with BSA

Cationic poly(amidoamine)s (PAAs) were synthesised and characterised by NMR and gel permeation chromatography. Their thermal properties were investigated using thermogravimetric analysis and differential scanning calorimetry. Although poly(amidoamine)s have been used as endosomolytic polymers for protein intracellular delivery, the interaction of the polymers with the proteins still need to be investigated. BSA was used as a model protein and complexation with the different poly(amidoamine) s was investigated using gel retardation assays, fluorescence spectroscopy and high sensitivity differential scanning calorimetry. Our results indicate that the thermal stability of BSA was affected upon interaction and complexation with the poly(amidoamine)s, however these interactions did not seem to modify the structure of the protein. Polymer flexibility seemed to favour polymer/protein complexation and promoted thermal stability

Synthesis and in vitro Bioactivity of Polyunsaturated Fatty Acid Conjugates of Combretastatin A-4

Combretastatin A-4 (CA-4) (1) is a plant-derived anticancer agent binding to the tubulin colchicine site. Polyunsaturated fatty acids (PUFA) are readily taken up by cancer cells and have been used to improve cell targeting. In the present study, four CA-4-PUFA conjugates were synthesized by coupling combretastatin A-4 (1) with several polyunsaturated fatty acids. The conjugates (2a-d) were characterized using spectroscopic methods. Their cytotoxicity was evaluated against human breast cancer cells (MCF-7) and the inhibition of tubulin polymerization was determined in vitro. All conjugates influenced tubulin polymerization with the arachidonic acid conjugate (2c) displaying cytotoxicity similar in potency to the natural product CA-4 (1)