عنوان به زبان ديگر :
The Identification of Toxicophores for the Prediction of Mutagenicity , Hepatotoxicity and Cardiotoxicity
پديد آورندگان :
Hakimelahi GH نويسنده , Khodarahmi GA نويسنده
چكيده لاتين :
The toxic properties of compounds can be related to chemical structures. and more specifically. to particular substructures.
called toxicophores. Reliability and accuracy of mutagenicity. hepatotoxicity. or cardiotoxicity predictions may be achieved by
identifying toxicophores. These predictions can guide the design of chemical libraries for hit and lead optimization. As such. a
thorough molecular knowledge in drug-induced toxicity is required to aid the development of new therapeutic agents and prevent
the release of potent ially toxic drugs onto the market. The incorporation of these potentially reactive chemical moieties within
new therapeutic agents should be limited. This. however. can not always be prevented. particularly when the structural feature
responsible for toxicity is also responsible for the pharmacological efficacy.
In recent years. there has been strong pressure from society in general. and from govern ment agencies in particular. to
develop "general" prediction models in order to cope with the thousands of chemicals present in the environment for which
experimental data arc not available and likely will never exist. Therefore. one of the objectives of this work is to introduce
methodologies capable of identifying the potential environmental health hazards of chemicals. This review also summarizes the
evidence for reactive metabolite formation from chemical carcinogens. hepatotoxic drugs. and also describes how and where
molecules bind and inhibit hERG K+channels. causing cardiotoxicity by QT prolongation. Such information should dramatically
improve our understanding of drug-induced toxic reactions. Indeed. pharmaceutical companies are striving to improve the drug
discovery and development process to identify. as early as possible, the risk of novel agents. or their metabolites. causi ng
mutagenicity. hepatocellular toxicity. or QT interval prolongation and to make appropriate go/no-go decisions or modify their
development programs accordi ngly
