A Round Trip from Medicinal Chemistry to Predictive Toxicology.
Predictive toxicology is a new emerging multifaceted research field aimed at protecting human health and environment from risks posed by chemicals. Such issue is of extreme public relevance and requires a multidisciplinary approach where the experience in medicinal chemistry is of utmost importance. Herein, we will survey some basic recommendations to gather good data and then will review three recent case studies to show how strategies of ligand- and structure-based molecular design, widely applied in medicinal chemistry, can be adapted to meet the more restrictive scientific and regulatory goals of predictive toxicology. In particular, we will report: Docking-based classification models to predict the estrogenic potentials of chemicals. Predicting the bioconcentration factor using biokinetics descriptors. Modeling oral sub-chronic toxicity using a customized k-nearest neighbors (k-NN) approach.
Dipartimento di Farmacia - Scienze del Farmaco, Università degli Studi di Bari "Aldo Moro", Via E. Orabona 4, 70125, Bari, Italy.
Giuseppe Felice
GF
Mangiatordi
Dipartimento di Farmacia - Scienze del Farmaco, Università degli Studi di Bari "Aldo Moro", Via E. Orabona 4, 70125, Bari, Italy.
Angelo
A
Carotti
Dipartimento di Farmacia, Università degli Studi di Napoli "Federico II", Via D. Montesano 49, 80131, Napoli, Italy.
Ettore
E
Novellino
Dipartimento di Farmacia - Scienze del Farmaco, Università degli Studi di Bari "Aldo Moro", Via E. Orabona 4, 70125, Bari, Italy. orazio.nicolotti@uniba.it.
Orazio
O
Nicolotti
D000465:Algorithms; D003198:Computer Simulation; D015195:Drug Design; D006801:Humans; D008954:Models, Biological; D008962:Models, Theoretical; D062105:Molecular Docking Simulation / Q000379:methods*; D021281:Quantitative Structure-Activity Relationship; D059550:Toxicity Tests, Subchronic / Q000379:methods*
Bioconcentration factor; Biokinetics descriptors; Docking-based classification models; Estrogenic potentials of chemicals; Oral sub-chronic toxicity