IN SILICO TOXICITY PREDICTION OF TROGLITAZONE, ROSIGLITAZONE AND PIOGLITAZONE USING DEREK NEXUS

The objective of this study was to determine the toxicity potential of three thiazolidinediones (troglitazone, rosiglitazone and pioglitazone) using in silico expert system DEREK Nexus. The chemical structures of troglitazone, rosiglitazone and pioglitazone were processed using the DEREK Nexus system on computer using all the rules in the knowledge base for predicting multiple toxicity end points in multiple species including human. DEREK Nexus was able to make predictions for all three drugs (troglitazone, rosiglitazone and pioglitazone) in the exercise. The DEREK software generated the toxicity alerts for hepatotoxicity and mitochondrial dysfunction for all three drugs. In addition, the results of troglitazone indicated alerts for carcinogenicity and skin sensitization. The level of alerts was different for different toxicity end points and species. The alert for hepatotoxicity and mitochondrial dysfunction correlated well with the information available in literature indicating its utility in prediction of the potential toxicity for the drug candidates at an early stage of development. However, it is important to note that the in silico data should be interpreted in conjunction with the in vitro and in vivo toxicity study results for the better predictivity of the potential risks to humans. Keywords: Troglitazone, Rosiglitazone, Pioglitazone, DEREK, In Silico.