GENOTOXIC EVALUATION OF 2,2'-(PIPERAZINE-1,4-DIYL) BIS[N-(2,6-DIMETHYLPHENYL)] ACETAMIDE AN IMPURITY OF RANOLAZINE

Shebin John* and Dr. Pramila T.

ABSTRACT

The prediction of compound toxicities is an important part of the drug design development process. Computational toxicity estimations are not only faster than the determination of toxic doses in animals but can also help to reduce the amount of animal experiments. ProTox, a virtual tool for the prediction of toxicities of small molecules. ProTox incorporates molecular similarity, fragment propensities, most frequent features and (fragment similarity-based CLUSTER cross-validation) machine-learning, based a total of 33 models for the prediction of various toxicity endpoints such as acute toxicity, hepatotoxicity, cytotoxicity, carcinogenicity, mutagenicity, immunotoxicity, adverse outcomes (Tox21) pathways and toxicity targets. This present study explains the genotoxic evaluation of 2,2'-(piperazine-1,4-diyl) bis[N-(2,6-dimethylphenyl)] acetamide an impurity of ranolazine and the result concludes that there is no literature report on genotoxicity, mutagenicity or carcinogenicity for this ranolazine impurity 2,2'-(Piperazine-1,4-diyl) bis[N-(2,6-dimethylphenyl)] acetamide This compound is potentially less genotoxic based on consensus of structural alert and QSTR models.

Keywords: Carcinogenicity, Cytotoxicity, Genotoxicity, Impurity, Mutagenicity, Ranolazine.