Maestro 9.4 as a tool in the structure based screening of glycoalkaloids and related compounds, targeting aldose reductase

Abstract

Diabetes mellitus is one of the alarming common diseases of this century. In India, according to the statistics of the International Diabetes Federation, 87 million of people are affected by Diabetes mellitus and this number is expected to cross 100 million by 2030. This has created a thrust for the development of new medicines. Recently, ban of pioglitazone, an oral anti-diabetic drug by Drugs Technical Advisory Board (DTAB) on account of its side effects, portrays the need for developing new drugs with less or no side effects. Cheminformatics tools assist in screening several millions of compounds and providing lead compounds in drug designing. This paper focuses on screening of lead compounds in arriving at newer drugs for Diabetes mellitus. Aldose reductase a cytosolic enzyme is the receptor to which selected lead compounds are docked. Glycoalkaloids (present in bitter melon) and related compounds were docked onto aldose reductase and based on the GLIDE score, structural modifications were carried out to arrive at the highest GLIDE score. A commercially available molecule recommended for Type 2 Diabetes mellitus was also taken for reference. Glycoalkaloids were found to possess high GLIDE score compared to standard. In order to analyze the competence of the Schrodinger software a comparison was made with an internet freeware Hex 6.3 version. The flexible receptor docking of Schrodinger was found to be more advantageous than the Hex 6.3.