Molecular Pharmacology and Pathology of Strokes PDF Free Download
While currently used anti-platelet drugs such as aspirin and clopidogrel demonstrate efficacy in many patients, they exert undesirable side effects. Therefore, the development of effective therapeutic strategies for the prevention and treatment of thrombotic diseases is a demanding priority. Recently, precious metal drugs have conquered the subject of metal-based drugs, and several investigators have moved their attention to the synthesis of various ruthenium (Ru) and iridium (Ir) complexes due to their prospective therapeutic values. In this Special Issue, the authors Hsia et al.  found that Ir (III)-derived complex, (Ir-11), showed potent antiplatelet activity by inhibiting platelet activation through the suppression of the phosphorylation of phospholipase Cγ2 (PLCγ2), protein kinase C (PKC) cascade and the subsequent suppression of Akt and mitogen-activated protein kinases (MAPKs) activation, ultimately inhibiting platelet aggregation. A detailed in vitro antiplatelet, in vivo antithrombotic and structure-activity relationship (SAR) study was performed on newly synthesized Ir complexes, Ir-1, Ir-2 and Ir-4, in agonists-induced human platelets . This study found that Ir-1 expressively suppressed collagen-induced Akt, PKC, p38MAPKs and JNK phosphorylation. Interestingly, platelet function analyzer (PFA-100) showed that Ir-1 caused a significant increase in collagen-adenosine diphosphate (C-ADP) induced closure times in mice, but Ir-2 and 4 had no effect on these reactions. Moreover, Ir-1 significantly prolonged the platelet plug formation, increased tail bleeding times and reduced the mortality of adenosine diphosphate (ADP)-induced acute pulmonary thromboembolism in mice. Ir-1 has no substitution on its phenyl group; a water molecule (like cisplatin) can replace its chloride ion and, hence, the rate of hydrolysis might be tuned by the substituent on the ligand system. These features might have played a role for the observed effects of Ir-1. These results indicate that Ir compounds may be a lead compound to design new antiplatelet drugs for the treatment of thromboembolic diseases.