PO-35 - Designing of the new antithrombotic and also anticancer gold complexes

Drugs which are effective on P2Y12 receptor downregulation may be significantly profitable in more than one way. Firstly, P2Y12 inhibition down regulates HIF1a activity which is important in both angiogenesis and metastasis processes. HIF1a also increases tumour cells' resistance to cytotoxic therapy by increasing their ability to recover from DNA damage; so inhibiting HIF1a activity via P2Y12 pathway both increases cytotoxic activity of chemotherapy and helps in the prevention of tumour spread. Another factor that affects tumour growth and spread is platelet activity. Recent research supposes that platelet activity is also important for tumour's growth, vessel proliferation and metastatic potential. Inhibiting P2Y12 is proposed to decrease platelet activity in malignant microenvironment, thus preventing the processes listed above. There are two more findings that support the potential efficiency of P2Y12 inhibition. ATP is a known antagonist at P2Y12 receptor; thus animal studies that show ATP's anti-cancer effect are promising for the efficiency of drugs working on this pathway. Another drug affecting P2Y12 is prasugrel, research also shows that prasugrel use decreases tumorigenesis risk. As a result it might be said that the studies on these drugs that work on P2Y12 pathway can be considered as indicators for the potential efficiency of drugs inhibiting this receptor (1-11). On the other hand, coordination of bioactive molecules to metal centres may result greater therapeutic effect. Especially, the gold complexes are interesting in the field of medicinal inorganic chemistry as candidate agents for the treatment of different diseases and attracted attention as potential anti-tumour drugs. There is a rich literature about the gold(III) complexes including activity in cisplatin-resistant cancers, their synergistic administration and those with an affinity for specific biological targets such as mitochondria and DNA (12-19).

In the light of these knowledges, our aim is to find novel metal complexes which could potentially overcome the hurdles of current clinical drugs including antithrombotic and also antitumor activities.

In this study the gold(III) complexes of Prasugrel were synthesized. The characterization of the intermediate and final compounds determined by using 1H NMR, MS, IR spectroscopic methods and elemental analysis.

Spectrums indicated the separations and densities in aromatic regions due to steric, conjugative and inductive influences. The achieved data from elemental analyses 1H NMR, IR and MS were as expected.

Thienopyridine gold complexes may have a synergic effect of the inhibition of important enzymes for P2Y12 receptor inhibition and also DNA damage.