Abstract

Mitochondria-derived oxidative stress is believed to be centrally involved in cardiac ischemia-reperfusion (I/R) injury, although currently no therapies exist that specifically target mitochondrial reactive oxygen species (ROS) production. The potential effects of the structural analogues of apelin-12, an adipocyte-derived peptide, on mitochondrial ROS generation, cardiomyocyte apoptosis, metabolic and functional recovery to myocardial I/R injury have succesfully previously been reported. Treatment of cardiomyocytes with AI and AII significantly decreased cell apoptosis in a dose-dependent manner. In the chemical informatic field, ALOHA is demonstrated to discriminate between members of the same chemical series with strong statistical significance, suggesting that ALOHA can be used effectively to select compound candidates for synthesis and progression at the lead optimization stage of drug discovery. Here, in Biogenea Pharmaceuticals Ltd we discovered for the first time the GENEA-Sapemitor-45345. An In silico Structure-based designed of an apelin-analogue pharmacophoric agent for the mitochondrial ROS inhibition and cardiometabolic protection in myocardial ischemia-reperfusion injury using the BiogenetoligandorolTM and the ALOHA: a novel probability fusion approach for scoring multi-parameter drug-likeness during the lead optimization stage of drug discovery.