A simple approach discriminating cardio-safe drugs from toxic ones

More than 130 FDA-approved drugs have been identified for now to prolong the QT interval and possibly lead to suddencardiac death. Due to their toxic effect, some of these drugs have been withdrawn from the pharmaceutical market. In thisstudy, we have formulated few rules to assess the ability to prolong QT interval and thereby discriminate between cardiotoxicand -safe drugs. These rules have clearly determined that cardio-toxic drugs are more likely to obey Lipinski rule of 5and Oprea lead-like rule. Moreover, the cardio-toxic drugs have been found to have in common values of -0.5 to 6.5 log P,1-5 nitrogen atoms, up to 4 oxygen atoms, 5-27 hydrophobic atoms, and 15-53 single bonds. Matthews CorrelationCoefficient with the value of 0.6 was also attained and nearly 96% of the cardio-toxic drugs were successfully covered.Thus, despite the simplicity of this methodology, we have obtained interesting and informative results. The proposed set ofthese simple rules could be employed to infer cardio-toxicity or -safety for current and potential drugs. The present studywill have important impact on decision making in the fields of drug development, molecule screening in biological assays,and other applications as well.