2D-QSAR Study of 1,3,4-thiadiazole-2-arylhydrazone Derivatives: An Approach to Design Antitrypanosomal Agents

Megazol is a highly active compound against Trypanosoma cruzi, and has become a core structure for the design of new trypanocidal agent. Recently, a new potent trypanocide agent Brazilizone A (a derivatives of megazol), was identified which presents an IC50 two fold more potent than the prototype megazol. This result has encouraged us to perform QSAR study on structurally-related 1,3,4-thiadiazole-2-arylhydrazone derivatives (Brazilizones), in order to get a better understanding of their structural features and antiprotozoal activity. Here a QSAR studies were performed on a set of 29 analogs of 1,3,4-thiadiazole-2-arylhydrazone (Brazilizone A derivatives) using VLifeMDS science QSAR module by using Multiple Linear Regression (MLR), Principal Component Regression (PCR) and Partial Least Squares (PLS). Among these methods, Multiple Linear Regression (MLR) method has shown very promising result as compare to other two methods. The models developed gave good predictive correlation coefficient (r) of 0.9773, significant cross validated correlation coefficient (q) of 0.6415, F test of 71.742, r for external test set (pred_r) 0.6002, coefficient of correleation of predicted data set (pred_rse) 0.7438 and degree of freedom 11 by Multiple Linear Regression (MLR) method. The model developed to predict the structural features of 1,3,4-thiadiazole-2-arylhydrazone, revealed useful information about the structural features required for the molecules to inhibit Trypanosoma cruzi. Therefore, this study not only casts light on binding mechanism between Trypanosoma cruzi and its inhibitors, but also provides new hints for the design of antitrypanosomal agents with observable structural diversity.