Design and Synthesis of Esterase Activated Nitroxyl (HNO) Donor

Abstract

“ 1992 Molecule of the year “ nitric oxide (NO) is a signaling molecule that is biosynthesized from L-arginine by the help of nitric oxide synthases (NOS s) which are further categorized into three types based on their activity as, inducible (iNOS), endothelial (eNOS) and neuronal ( eNOS) synthases. The biological and chemical properties of NO have been studied for over an extended period of time in earlier days. The one electron reduced form of NO, nitroxyl ( HNO) came into the limelight recently and attracted a lot of interest in scientists due to its structural similarities with nitric oxide. But nitroxyl`s ability to undergo dimerization with itself to form N2O majorly became one of the first things to be tackled for studying its activity. Hence scientists started to design various HNO donors which can be use to study its activity in cells. Various physiological responses such as vasodilation, inhibition of platelet aggregation etc discovered as the responses for HNO activity inside cell as a result of it. But these donors often lack in terms of selectivity and presence of toxic by-products formed from them remained as the their major disadvantages. In this thesis,we design esterase triggerable HNO donor to tackle the aforementioned major problems. Since the by-protects from the compound after metabolism is not cytotoxic, it can be a good candidate for cellular studies for HNO in cells. The release of HNO from the compounds were able to confirm with the help of fluorescence assay too.