THE LEAF ALKALOID OF CATHARANTHUS ROSEUS LINN. AS ANTIDIABETIC POTENTIAL: IN SILICO APPROACH THROUGH QUANTITATIVE STRUCTURE ACTIVITY RELATIONSHIP MODELLING AND MOLECULAR DOCKING

Abstract

The medicinal herb, Catharanthus roseus Linn. is commonly known as Nayantara in Bengali and the extract of leaf is used for the prevention of type 2 diabetes (T2D) traditionally. The aim of study was to detect acute oral toxicity of rat by quantitative structure activity relationship (QSAR) modelling and identification of lead small molecule by molecular docking for antidiabetic phytocompounds (alkaloids). In silico study to detect rat oral acute toxicity of 12 phytocompounds and 2 common synthetic medicines by using ProTox-II webserver and receptor-ligand binding energy and interaction through molecular docking for phytocompounds present in C. roseus on tyrosine phosphatase 1B or TP1B (PDB ID: 2BGD) as causative agent for T2D. The molecular docking was performed by using PyRx tool (Version 0.8) to know favorable binding affinity and energy. The molecular interaction was visualized through molecular graphics laboratory (MGL) tool (Version 1.5.6). Present predictive study revealed that Yohimbine (40mg/Kg) obtained high acute toxicity value (LD50) as class II and Glibenclamide (3250mg/Kg) as class V among 14 compounds. The molecular docking showed favorable binding energy in Ibogaine (-8.1Kcal/mol) followed by Yohimbine (-7.9Kcal/mol) when compared to synthetic medicines viz. Glibenclamide (-7.9 Kcal/mol) and Metformine (-5.0Kcal/mol) were obtained on TP1B receptor. In conclusion, the predictions showed Ibogaine could be a suitable lead candidate, which can prevent T2D. The binding was obtained at the active site and this phytoligand can be used for suitable inhibition of TP1B. It is suggested to validate the present prediction with experimental toxicology and pharmacological assay in future.