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.

Grantor dc:publisher

Università degli Studi di Cagliari

Year dc:date

2016

Author dc:creator

• ARRIDU, ANTONELLA

• anticancer
• antitumorali
• design
• progettazione
• sintesi
• synthesis
• Settore CHIM/08 - Chimica Farmaceutica

Statement dc:rights

• info:eu-repo/semantics/openAccess
• license:Non specificato

Language dc:language

eng

Handle dc:identifier

http://hdl.handle.net/11584/266708

OAI identifier oai:identifier

oai:iris.unica.it:11584/266708