Design and synthesis of new potential anticancer agents and high-selective A2B antagonists

The synthesis of antitumor agents covers a large part of current medicinal chemistry efforts. This thesis mainly focuses on the synthesis of different scaffolds as new potential anticancer agents. Two different approaches were applied: a hybrid concept and a rational based drug design. In the first case, the hybrid concept is useful since it allows combining multiple active scaffolds in a unique molecule. As a consequence, several targets could be hit simultaneously, making this solution particularly attractive for multi-factorial diseases like cancer. Within this category, several isatin-thiazolinone-pyrazoline hybrids were synthesized. Some of them were submitted to biological assays, demonstrating good activity toward different solid tumour cell-lines. In the second class of compounds, the synthetic efforts were combined to computational tools in order to achieve detailed information about the structure-activity relationships. Following this approach, psoralen derivatives, thought as DNA G-quadruplex stabilizers, were synthesized. For these compounds no biological assays were performed so far. Finally, the last part of the thesis has been dedicated to the synthesis of 1-alkyl-8-(piperazine-1-sulphonyl)phenyl xanthines as high-selective A2B antagonists. Even though the leading role of adenosine and their receptors in cancer pathogenesis were extensively documented, the high therapeutic potential of these compounds requires a wider analysis of their pharmacological properties. Also in this case, several compounds were synthesized. Some of them were tested in a radioligand binding assay to evaluate the affinity and selectivity toward A2BR subtype, further confirming the high potential of these compounds as A2B antagonists.