QSAR of Oxazinanone Derivatives As 11-Β Hydroxysteroid Dehydrogenase Type 1 Inhibitor A Potent Anti Diabetic Agent

Abstract

11-β hydroxysteroid dehydrogenase type 1 is a key enzyme accountable for the interconversion of physiologically inert cortisone to active cortisol thus presents an effective target for the development of pharmacologically active anti diabetic agents focused on manage blood glucose levels, improve insulin sensitivity. The 11β-HSD1 facilitates intracellular cortisol construction that have a disease-causing role in type 2 diabetes and the co-morbidities that it causes. Drugs in habiting the enzyme 11 β-HSD1 offers a potential therapy to lessen the type 2 diabetes. Oxazinanone ring has shown activities as antitumor, antihypertensive, antibacterial, anti-inflammatory, antioxidant and many more. Oxazinanone ring have emerged as potent inhibitors of 11β-HSD1 enzyme. QSAR of Oxazinanone derivatives is performed with a goal of elucidating the key characteristics that cause their anti-diabetic action. QSAR is the most widespread method to ligand-based drug design. It is supposed that structures of the molecules are directly proportional with biological activities, and thus, the biological activities can be altered with any structural changes. The process involves computational or mathematical models to find important correlations between a series of structures and functions. Step wise partial least square, multiple linear regressions, and feed forward neural network were used in a QSAR investigation on enzyme (IC50 nM). The developed models were cross confirmed by the ‘‘leave one out’’ method. The model reveals the significance of steric parameter Verloop B1 (Substitution 1) and Total lipole molecular descriptor.Total lipole bear a resemblance to lipophilicity which is a ratio of the capability of molecules to transfer between oily partition and aqueous partition. These descriptors will have an impact on the design and expansion of novel anti-diabetic 11-hydroxysteroid dehydrogenase type 1 inhibitors.