Endothelial dysfunction (ED) is currently recognized as a key pathogenic factor in the development of cardiovascular diseases. Reduced bioavailability of nitric oxide (NO), increased oxidative and nitrosative stress, and disruption of redox homeostasis contribute to vascular endothelial damage, leading to ischemic, hypertensive, and neurodegenerative conditions. Currently, there is no pharmacotherapy specifically targeting ED, highlighting the urgent need for novel therapeutic agents with endothelioprotective properties.
This study highlights the rationale and experimental basis for the creation of a new class of pharmacological agents—endothelioprotectors. Particular focus is given to a new compound, Angiolin (S)-2,6-diaminohexanoic acid 3-methyl-1,2,4-triazolyl-5-thioacetate, designed as an endothelioprotector with neuro- and cardioprotective capabilities. Structurally combining L-lysine and thiotriazoline fragments, Angiolin demonstrates a wide spectrum of pharmacological activities, including endothelioprotective, cardioprotective, neuroprotective, anti-ischemic, antioxidant, and anti-inflammatory effects.
Preclinical studies have shown that Angiolin enhances NO bioavailability, protects endothelial cells, preserves mitochondrial function, activates the glutathione system, and prevents oxidative damage in ischemic tissues. Furthermore, Angiolin improves cerebral and cardiac hemodynamics, promotes ATP production via the malate-aspartate shuttle, and modulates GABAergic neuroprotection by increasing pipecolic acid levels.
Toxicological assessment classifies Angiolin as a substance of low toxicity (Class VI), and Phase I clinical trials conducted with the approval of the Ministry of Health of Ukraine confirmed its safety profile. The compound represents a promising therapeutic strategy for complex treatment of chronic cerebral ischemia, myocardial infarction, heart failure, and prenatal hypoxia, offering advantages over current metabolitotropic drugs such as meldonium, piracetam, and trimetazidine.
In conclusion, Angiolin is a novel pharmacological agent with targeted endothelioprotective action and broad metabolic, cardio-, and neuroprotective potential, warranting further clinical investigation.
